Results of a national training programme in sentinel lymph node biopsy for breast cancer.

BACKGROUND: New Start, a structured, validated, multidisciplinary training programme in sentinel lymph node biopsy (SLNB), was established to allow the introduction and rapid transfer of appropriate knowledge and technical skills to ensure safe and competent practice across the UK. METHODS: Multidisciplinary teams attended a theory/skills laboratory course, following which they performed 30 consecutive SLNBs, either concurrently with their standard axillary staging procedure (training model A) or as stand-alone SLNB (training model B). SLNB was performed according to a standard protocol using the combined technique of isotope ((99m) Tc-labelled albumin colloid) and blue dye. An accredited New Start trainer mentored the first five procedures in the participant's hospital, or all 30 if stand-alone. Validation standards for model A and B were a localization rate of at least 90 per cent. In addition, for model A only, in which a minimum of ten patients were required to be node-positive, a false-negative rate (FNR) of 10 per cent or less was required. RESULTS: From October 2004 to December 2008, 210 SLNB-naive surgeons, in 103 centres, performed 6685 SLNB procedures. The overall sentinel lymph node (SLN) localization rate was 98·9 (95 per cent confidence interval 98·6 to 99·1) per cent (6610 of 6685) and the FNR 9·1 (7·9 to 10·5) per cent (160 of 1757). The FNR was related to nodal yield, ranging from 14·8 per cent for one node and declining to 9·7, 6·6, 4·7 and 4·1 per cent for two, three, four and more than four SLNs respectively. No learning curve was identified for localization or FNR. CONCLUSION: The programme successfully trained a wide range of UK breast teams to perform safe SLNB and suggested that a standard injection protocol and structured multidisciplinary training can abolish learning curves.

Training of staff for the delivery of PET/CT services in the UK.

Evidence for the cost effectiveness of PET/CT imaging is now driving the widespread introduction of PET/CT services throughout the UK. The provision of PET/CT facilities will require a workforce of medical, scientific, technical and engineering staff who are adequately trained and fit for purpose. Suitably trained staff in this speciality are scarce. The development and accreditation of training courses and other educational resources for training programmes in all disciplines will therefore be required at a national and regional level. The implementation of PET/CT training can be achieved more cost-effectively by developing multi-professional learning resources whenever possible. It is intended that the recommendations would be implemented by close co-operation of both public and private healthcare providers together with educational establishments.

Radioisotope bone scans in the preoperative staging of hepatopancreatobiliary cancer.

BACKGROUND: The aim of the study was to determine the value of radioisotope bone scans in the preoperative staging of patients with hepatopancreatobiliary (HPB) cancer. METHODS: Bone scanning was performed as part of a routine staging protocol in 402 consecutive patients with HPB cancer over a period of 5 years. Patients with positive bone scans underwent coned radiography, computed tomography with review on bone windows, or a bone biopsy. Bone scans were reviewed along with staging investigations, surgical and histological findings. Patients were followed for a minimum of 6 months. RESULTS: There were 171 patients with colorectal liver metastases, 106 with suspected pancreatic cancer, 47 with hepatocellular cancer, 52 with gallbladder cancer or cholangiocarcinoma, and 26 with other types of HPB cancer. Bone scans were negative in 377 patients (93.8 per cent) and positive in 25 patients (6.2 per cent). Of the 25 positive scans, 16 were falsely positive as a result of degenerative bone disease. Of nine patients with a true-positive bone scan, four had locally irresectable disease and four distant metastases. In only one patient did the bone scan result alone influence the decision to resect the HPB cancer. Overall sensitivity was 100 per cent, specificity 95.9 per cent, positive predictive value 36.0 per cent and negative predictive value 100 per cent. CONCLUSION: Bone scanning should not be included in the routine staging protocol for HPB cancer.

Calculated glomerular filtration rate is a useful screening tool to identify scleroderma patients with renal impairment.

OBJECTIVES: Although it only occurs in a minority of patients, renal involvement is a life-threatening complication of scleroderma (SSc). We have investigated the utility of two formulae to calculate glomerular filtration rate (GFR) in a population of SSc patients. METHODS: Twenty-six patients (20 female, 6 male, median age 58 yr, age range 12-80 yr) satisfied our criteria for inclusion in a retrospective comparison of measured and calculated GFR. GFR was measured using (51)Cr-EDTA. The modified Cockcroft and Gault formula and equation 7 from the Modification of Diet in Renal Disease (MDRD) were used to calculate GFR. RESULTS: Eighteen out of 19 patients analysed with a serum creatinine concentration less than the upper limit of the normal range had a measured GFR outside the normal range. Three patients with a normal creatinine concentration had a measured GFR <60 ml/min and in each of these the calculated GFR was also abnormal. All patients with a measured GFR <60 ml/min were identified using both the MDRD and the modified Cockcroft and Gault formula to calculate GFR. The greatest correlation between measured and calculated GFR was seen when the MDRD formula, which employs demographic and serum variables, was used in patients with body surface area (BSA) >1.4 m(2) who were not taking Iloprost (r=0.91). Use of the Cockcroft and Gault formula to calculate creatinine clearance with a correction factor for GFR, the inclusion of patients taking Iloprost and the inclusion of patients with BSA <1.4 m(2) were all associated with a lower degree of correlation. CONCLUSION: Serum creatinine is a poor marker of renal function in SSc patients. Calculating GFR from demographic and serum variables is a simple technique to identify SSc patients who have abnormal renal function. The authors recommend the use of the MDRD formula.

A phase I trial of antibody directed enzyme prodrug therapy (ADEPT) in patients with advanced colorectal carcinoma or other CEA producing tumours.

Antibody-directed enzyme prodrug therapy is a targeted therapy in which a prodrug is activated selectively at the tumour site by an enzyme, which has been targeted to the tumour by an antibody (antibody-enzyme conjugate). Previous clinical trials have shown evidence of tumour response, however, the activated drug had a long half-life, which resulted in dose-limiting myelosuppression. Also, the targeting system, although giving high tumour to blood ratios of antibody-enzyme conjugate (10 000 : 1) required administration of a clearing antibody in addition to the antibody-enzyme conjugate. The purpose of this current study therefore was to attempt tumour targeting of the antibody-enzyme conjugate without the clearing antibody, and to investigate a new prodrug (bis-iodo phenol mustard, ZD2767P) whose activated form is highly potent and has a short half-life. Twenty-seven patients were treated with antibody-directed enzyme prodrug therapy using A5CP antibody-enzyme conjugate and ZD2767P prodrug, in a dose-escalating phase I trial. The maximum tolerated dose of ZD2767P was reached at 15.5 mg m(-2)x three administrations with a serum carboxypeptidase G2 level of 0.05 U ml(-1). Myelosuppression limited dose escalation. Other toxicities were mild. Patients' quality of life was not adversely affected during the trial as assessed by the measures used. There were no clinical or radiological responses seen in the study, but three patients had stable disease at day 56. Human anti-mouse antibody and human anti-carboxypeptidase G2 antibody were produced in response to the antibody enzyme conjugate (A5CP). The antibody-enzyme conjugate localisation data (carboxypeptidase G2 enzyme levels by HPLC on tumour and normal tissue samples, and gamma camera analysis of I-131 radiolabelled conjugate) are consistent with inadequate tumour localisation (median tumour: normal tissue ratios of antibody-enzyme conjugate of less than 1). A clearance system is therefore desirable with this antibody-enzyme conjugate or a more efficient targeting system is required. ZD2767P was shown to clear rapidly from the circulation and activated drug was not measurable in the blood. ZD2767P has potential for use in future antibody-directed enzyme prodrug therapy systems.

Can scintimammography with (99m)Tc-MIBI identify multifocal and multicentric primary breast cancer?

Scintimammography with (99m)Tc-MIBI has been shown to be an effective adjunct to imaging of the breast with mammography. Uptake of (99m)Tc-MIBI is particularly high in sites of non-calcified cancer and ductal carcinoma in situ (DCIS), and as a consequence it may be possible to use this method of imaging in identifying multifocal or multicentric disease. The aim of this study was to evaluate the efficacy of preoperative scintimammography in the detection of multifocal and multicentric breast cancer and compare these results with mammography. A retrospective review was performed of 353 women imaged with (99m)Tc-MIBI as part of the clinical assessment of their suspected primary breast cancer. The results of the scintimammography and mammography were then compared with the final pathological diagnosis obtained after mastectomy in all patients. Histopathological assessments of breast tissue from mastectomy confirmed 40 women (12%) had multifocal (34) or multicentric (six) breast cancer. Scintimammography correctly identified 39 of these cancers and the multifocal or multicentric character of the cancer was identified in 22 (52%) of these patients. Anatomical imaging performed in all 40 patients including 25 with mammography alone, mammography and ultrasound in 11 cases and ultrasound alone in four patients. Anatomical imaging identified cancer to be present in 28 patients (70%) and the combination of mammography and ultrasound identified correctly that the cancer was multifocal or multicentric in eight patients (22%). In this study scintimammography was able to identify more cases of multifocal and multicentric cancer than mammography and/or ultrasound. In patients where pre-operative identification of multicentric or multifocal disease can alter treatment scintimammography may be a useful investigative tool.

Prediction of the usefulness of combined mammography and scintimammography in suspected primary breast cancer using ROC curves.

UNLABELLED: The aim of this study was to compare the accuracy of 99mTc-methoxyisobutylisonitrile scintimammography (SMM) and conventional mammography in patients presenting with suspected primary breast cancer. Receiver-operating-characteristic (ROC) curve analysis was applied to determine if a combination of x-ray mammography (XMM) and SMM was more accurate than a single test alone. METHODS: The results of SMM, XMM, and a combination of both studies performed over a 3-y period on 374 suspicious lesions in 353 patients with no previous history of breast cancer were reviewed. Each scan report was reviewed and graded as follows: grade 1, definitely normal or benign; grade 2, probably normal or benign; grade 3, equivocal; grade 4, probably cancer; and grade 5, definitely cancer. The results were verified by pathologic examination of biopsy material obtained from each suspicious mass. ROC curves were generated from these results. RESULTS: There were 204 malignant breast tumors and 170 nonmalignant breast lesions. SMM diagnosed correctly 181 breast cancers and was true-negative in 122 benign breast lesions: sensitivity, 89%; specificity, 71%; positive predictive value (PPV), 79%; and negative predictive value (NPV), 84%. XMM diagnosed correctly 143 malignant tumors and was true-negative in 117 nonmalignant lesions. The sensitivity, specificity, PPV, and NPV for XMM were 70%, 69%, 73%, and 66%, respectively. Using a combination of the two tests, the combined sensitivity was 93%, specificity was 72%, PPV was 80%, and NPV was 90%. Using the index of the area under the ROC curve obtained by the rating method showed that the combination of XMM and SMM was significantly more accurate than either of the individual tests if performed alone (P < 0.05). CONCLUSION: This study shows that the combination of XMM and SMM produces more accurate results than either modality alone. Therefore, if there is doubt about the accuracy of XMM, SMM should be used as the second-line test in breast imaging.

The role of scintimammography and mammography in recurrent breast cancer. Evaluation of their accuracy using ROC curves.

BACKGROUND: With the increasing demand for breast conservation surgery, the probability of recurrent tumour within the breast increases. Traditionally x-ray mammography (XMM) was used to assess the post-surgical breast, but post-surgery and radiotherapy changes have reduced the accuracy of this method. Scintimammography (SMM) has also been proposed and appears to be more accurate than XMM. MATERIAL AND METHODS: A total of 101 women received (Tc99m) MIBI SMM and 88 had a subsequent XMM. There were 142 sites suspected of loco-regional recurrence breast cancer. During the study the patients did not receive any treatment other then hormonotherapy. SMM was performed by the standard Diggles-Khalkhali method and XMM was performed using standard 2 views. Analysis was performed and the results of each type of imaging compared with histology. In the ROC curve analysis 5 points of certainty were used: from 1 being definitely normal to 5 being definitely cancer; grades 4 and 5 were counted as positive. RESULTS: The overall sensitivity value of SMM was 84% and specificity was 85%, compared with a sensitivity of 52% for XMM and a specificity of 84%. Analysis of areas under ROC curves provides statistically significant difference between SMM and XMM (p < 0.05). Combining the two tests did not significantly improve the diagnostic accuracy of sequence imaging over SMM. CONCLUSION: ROC curve analysis demonstrates that scintimammography should be the primary investigation in suspected local recurrence following breast conservation surgery.

Comparison of functional imaging and standard CT in evaluation of disease extent in patients with tumours showing neuroendocrine features.

BACKGROUND: The diagnostic approach that should be used in disseminated neuroendocrine tumours (NET) remains a significant clinical problem. A novel approach has been the use of 111In Octreotide as functional imaging to find NETs. Therefore, the aim of this retrospective study is to report our comparison with direct CT as standard anatomical imaging. MATERIAL AND METHODS: A total of 48 patients (aged 16-79 years; mean age 55, SD 14 years) were imaged using both techniques with final histological confirmation of NET. Histology was as follows: 26 carcinoids; 2 pheochromocytomas; 4 gastrinomas, 1 islet tumour; 2 paragangliomas, 1 modullary carcinoma of the thyroid, 8 undetermined NET and 4 other tumours with signs of neuro-ectodermal cancers (2 hepatocellular carcinomas (HCC), fibrolamellar HCC and fibrous tumour). All patients had (111)In Octreotide and 30 had (123)I mIBG scans followed by spiral CT with contrast enhancement. 26 patients had single functional scans and 22 had multiple, up to 6 scans. Extent of disease as number of lesions was compared between CT and octreotide. RESULTS: CT was the best modality in 11 patients, in 6 it was as good as (111)In Octreotide. mIBG was the best in 6 patients; in 3 patients mIBG was as good as octreotide study. In 22 patients (111)In Octreotide was the most effective modality. In one patient there was no advantage with any of the tests. Comparison of the number of organs involved indicated that an octreotide study was much more effective than CT scanning (Wilcoxon matched pairs test, p < 0.001) and also the overall number of lesions detected using (111)In Octreotide was greater than with CT (Wilcoxon Matched Pairs test p < 0.01). CONCLUSION: Our results confirm the recommendation of the European NET group that functional imaging should be performed in patients with suspected NET.

The clinical application of a dual head gamma camera with coincidence detection in 20 women with suspected ovarian cancer.

OBJECTIVE: To assess the effectiveness of a dual head coincidence gamma camera in identifying ovarian cancer as a less expensive alternative to the traditional 2-[18F] fluoro-2-deoxy-D-glucose (18FDG) system using positron emission tomography. DESIGN: Prospective study. POPULATION: Twenty consecutive women suspected of having ovarian carcinoma. Inclusion was based on abnormal serum CA125 (reference range is 0-35 units/L), ultrasound, computerised tomography or clinical findings. METHODS: Women underwent assessment before staging laparotomy. Two nuclear medicine physicians, who were blinded to the pre-operative assessment, reported on 18FDG- dual head coincidence gamma camera imaging. MAIN OUTCOME MEASURES: The histology and operative staging were compared with the 18FDG- dual head coincidence gamma camera findings. RESULTS: Twelve women had pelvic malignancies (nine primary and three recurrences), seven women had benign pathology and one patient had a borderline malignancy. We were able to image accurately all malignant pelvic masses with dual head coincidence gamma camera, as well as accurately demonstrate disease spread. Two of the benign pelvic masses localised 18FDG. The positive predictive value for detecting malignancy was 86%. CONCLUSIONS: Dual head coincidence gamma camera offers accurate and affordable imaging in suspected ovarian masses, with improved specificity over CA125, ultrasound and computerised tomography. These results are similar to those obtained on more expensive dedicated PET systems. We report on a series of patients believed to have primary or recurrent carcinoma and recognise the need to include patients more likely to have benign lesions to assess false positive results. However, we believe that dual head coincidence gamma camera is useful in the pre-operative assessment of women with suspected ovarian cancer.

Tc-99m MIBI in suspected recurrent breast cancer.

A prospective trial was performed to assess the accuracy of Tc-99m MIBI scintimammography in 63 women (mean age 65, range 33-85 years) with suspected recurrent breast cancer in the breast and/or loco-regional tissues. All patients had been diagnosed with breast cancer 1-23 years before the scintimammography. A total of 27 breasts had been removed by mastectomy so scintimammography was compared with mammography in the remaining 99 breasts. Pathological follow-up of patients confirmed 33 sites of recurrent disease within the breast, 26 (78%) were identified by scintimammography and 14 (42%) by mammography; 30 (90%) were positive on one test or the other. In addition Tc-99m MIBI scintimammography identified 10/16 (63%) of axillary lymph nodes with recurrent tumour and 4/6 sites of recurrent tumour present elsewhere. Tc-99m MIBI scintimammography is more accurate in identifying recurrent disease in the breast than mammography and can identify loco-regional recurrence outside of the breast.

Preoperative diagnosis of ovarian carcinoma with a novel monoclonal antibody.

OBJECTIVE: This study was undertaken to determine whether preoperative radioimmunoscintigraphy of complex ovarian masses with technetium Tc 99m MAb-170 (Tru-Scint AD; Biomira Inc, Edmonton, Alberta, Canada), a murine whole immunoglobulin G monoclonal antibody that has been found to have panadenocarcinoma affinity, would predict surgical findings. STUDY DESIGN: The age range of studied patients was 42 to 83 years (mean, 60.3 years). Planar computed tomographic imaging and single-photon emission computed tomographic imaging were performed at 15 minutes, 6 to 8 hours, and 18 to 24 hours after injection of 1000 MBq technetium Tc 99m MAb-170. Laparotomy was performed within 10 days. RESULTS: Eighteen patients had borderline or invasive ovarian cancers verified by histologic examination. All primary malignancies or deposits (including intrahepatic deposits) yielded positive results on radioimmunoscintigraphic imaging. Radioimmunoscintigraphy was able to identify serosal deposits not seen on computed tomographic or ultrasonographic scans. False-positive localization of the antibody was noted in 6 of the 9 patients with benign pathologic processes. CONCLUSION: It is possible to detect with technetium Tc 99m MAb-170 all patients who have cancer (including sites not seen on computed tomographic or ultrasonographic scan); however, the low specificity (33%) means that patients still require surgical verification of disease.