M. El-Sheemy

Monitoring the response of large (>3 cm) and locally advanced (T3-4, N0-2) breast cancer to neoadjuvant chemotherapy using 99mTc-Sestamibi uptake

Background and aim99mTc-Sestamibi (MIBI) scintimammography has an established role in the diagnosis of breast cancer. As a functional imaging technique, it may also be useful in assessing the response to chemotherapy. The aim of this study was to assess the effectiveness of the technique for this purpose. MethodsTwenty-six patients undergoing neoadjuvant chemotherapy for large or locally advanced breast cancer were monitored using the tumour to background ratio measured on MIBI scintimammograms. Patients were assessed and the size of the tumour was measured by callipers and ultrasonography before and at the end of treatment. Patients were assessed as complete, partial or non-responders. Following chemotherapy, patients proceeded to surgery with pathological evaluation of the operative specimen. ResultsTwenty-four of the 26 patients showed a reduction in MIBI uptake on completion of chemotherapy. Residual tumour was demonstrated on the scintimammogram in four patients and all had significant residual disease on histology. In the remaining 22 patients, the final scintimammogram was negative, although three patients were assessed as non-responders and had large residual tumours on histology. ConclusionA positive MIBI scan is highly predictive of the presence of significant residual disease on completion of chemotherapy. However, a negative MIBI scan does not rule out the presence of considerable residual tumour. Whereas ultrasound and clinical assessment may underestimate the response to chemotherapy, MIBI imaging tends to overestimate the response.

Generation in vivo of peptide-specific cytotoxic T cells and presence of regulatory T cells during vaccination with hTERT (class I and II) peptide-pulsed DCs

BackgroundOptimal techniques for DC generation for immunotherapy in cancer are yet to be established. Study aims were to evaluate: (i) DC activation/maturation milieu (TNF-α +/- IFN-α) and its effects on CD8+ hTERT-specific T cell responses to class I epitopes (p540 or p865), (ii) CD8+ hTERT-specific T cell responses elicited by vaccination with class I alone or both class I and II epitope (p766 and p672)-pulsed DCs, prepared without IFN-α, (iii) association between circulating T regulatory cells (Tregs) and clinical responses.MethodsAutologous DCs were generated from 10 patients (HLA-0201) with advanced cancer by culturing CD14+ blood monocytes in the presence of GM-CSF and IL-4 supplemented with TNF-α [DCT] or TNF-α and IFN-α [DCTI]. The capacity of the DCs to induce functional CD8+ T cell responses to hTERT HLA-0201 restricted nonapeptides was assessed by MHC tetramer binding and peptide-specific cytotoxicity. Each DC preparation (DCT or DCTI) was pulsed with only one type of hTERT peptide (p540 or p865) and both preparations were injected into separate lymph node draining regions every 2–3 weeks. This vaccination design enabled comparison of efficacy between DCT and DCTI in generating hTERT peptide specific CD8+ T cells and comparison of class I hTERT peptide (p540 or p865)-loaded DCT with or without class II cognate help (p766 and p672) in 6 patients. T regulatory cells were evaluated in 8 patients.Results(i) DCTIs and DCTs, pulsed with hTERT peptides, were comparable (p = 0.45, t-test) in inducing peptide-specific CD8+ T cell responses. (ii) Class II cognate help, significantly enhanced (p < 0.05, t-test) peptide-specific CD8+T cell responses, compared with class I pulsed DCs alone. (iii) Clinical responders had significantly lower (p < 0.05, Mann-Whitney U test) T regs, compared with non-responders. 4/16 patients experienced partial but transient clinical responses during vaccination. Vaccination was well tolerated with minimal toxicity.ConclusionAddition of IFN-α to ex vivo monocyte-derived DCs, did not significantly enhance peptide-specific T cell responses in vivo, compared with TNF-α alone. Class II cognate help significantly augments peptide-specific T cell responses. Clinically favourable responses were seen in patients with low levels of circulating T regs.

Optimization of %retention and %washout measurements of 99mTc sestamibi from breast tumours

Aim:Quantifying the %retention and %washout (%R&%W) of 99mTc sestamibi (MIBI) in breast cancer may allow prediction of response to chemotherapy. Many authors have investigated these parameters utilizing a wide variety of methods of quantification. The aim of this study is to determine the most accurate method of quantification. Method:Using an anthropomorphic phantom and a variety of tumour efflux rates, %R&%W were calculated using tumour only counts (T), tumour-to-background ratios (TBR), normalized TBR (nTBR) and background corrected counts (T - B) using images acquired at 0, 60, 120, 180 and 240 min post-injection. Results:T - B was the most accurate method of quantifying both %R&%W whilst TBR was the most inaccurate. The use of T was accurate when the tumour efflux rate was close to that of the normal breast and the inaccuracy increased as the difference between the tumour and normal breast efflux rates increased. The reverse was true when using nTBR as the accuracy increased as the difference between the efflux rates of tumour and normal breast increased. Time of image acquisition did not significantly alter accuracy. Conclusion:Background subtracted tumour counts must be used when quantifying the %retention or %washout of MIBI in breast cancer.

Does the uptake of 99mTc sestamibi in breast cancer predict clinical and ultrasound response to neoadjuvant chemotherapy

IntroductionThe uptake of 99mTc sestamibi (MIBI) is related to Pgp expression and multidrug resistance (MDR) in vitro. The aim of this study was to determine if measuring the tumour uptake of MIBI prior to neoadjuvant chemotherapy could predict those breast tumours that failed to respond to chemotherapy. MethodForty patients underwent scintimammography with MIBI prior to neoadjuvant chemotherapy. All 40 patients had clinical measurements of their tumours and 35 patients had ultrasound measurements, before and after chemotherapy. All patients were imaged at 10, 60 and 180 min post-injection and the tumour-to-background ratio was calculated using contralateral background ROIs. Responders were defined as a change of greater than 50% in the tumours largest dimension measured before and after chemotherapy. ResultsNo statistically significant difference was shown between the uptake in responders and non-responders at any of the imaging times. However, all patients assessed as non-responders with tumour to background ratios >2.0 showed other evidence of a response to chemotherapy. ConclusionThe uptake of MIBI does not allow the prediction of ultrasonographic or clinical response to chemotherapy. This is true for images acquired at 10, 60 and 180 min post-injection and tumour-to-background ratios calculated with contralateral background ROIs. However, all tumours with uptake of >2.0 were associated with a good response to chemotherapy.

A comparison of 18F-FDG double headed gamma camera PET, mammography and ultrasound in locally advanced breast cancer

AimsThe aims of this study were to assess the feasibility of gamma camera PET in a district general hospital (DGH) nuclear medicine department remote from a cyclotron and its performance compared to other imaging modalities in demonstrating disease in patients with locally advanced breast cancer, using histopathology as the ‘gold standard’. Methods18F-FDG was obtained from a production unit 100 miles from the imaging department. Twenty-five patients (mean age 72 years) with primary breast tumours measuring >2 cm on clinical examination were studied. All patients underwent triple assessment, i.e. clinical examination, imaging (mammography, ultrasound) and biopsy prior to PET imaging using an ADAC Solus camera with MCD capability. The PET images were reported blind and the results were compared with the results of the triple assessment and final histopathology. ResultsGCPET detected 24/25 primary breast tumours (sensitivity 96%). This compared with 22/25 for ultrasound and 15/25 for mammography. The lesion missed by PET was a grade 1 tumour, 8 mm in size. ConclusionGCPET is feasible in a DGH enabling a limited on-site PET imaging service to be provided. In cases of locally advanced breast cancer it is more sensitive than mammography or ultrasound and may provide additional information that could be important in planning the management strategy for some patients.

Effectiveness of 18F-FDG gamma camera PET in detecting metastatic lymph nodes in patients with locally advanced breast cancer?

Aim:The aim of this study was to assess the ability of double headed gamma camera PET (GCPET) using 18F-FDG in demonstrating metastases in the axillary lymph nodes of breast cancer patients and compare it with the ‘gold standard’ of histopathology. Methods:GCPET scanning with 18F-FDG was performed in 27 patients with locally advanced breast cancer (LABC) measuring >2 cm on clinical examination and/or palpable lymph nodes. The mean age of the patients was 68 years (range 43–83 years). All these patients underwent triple assessment involving clinical examination, imaging (mammography, ultrasound) and biopsy (FNAC and/or core cut). Following injection of 130 MBq of FDG, images were obtained using an ADAC Solus gamma camera with PET capability. The images were reported blind and the results were compared with the results of triple assessment and final histopathology. Results:Twenty-seven patients had histological assessment of their nodes (20 surgery, 7 core cut) and 12 had evidence of involved axillary lymph nodes. GCPET was positive in 10 cases (sensitivity=83%, specificity=100%). Both false negative lymph nodes had micrometastasis (<4 mm). Conclusion:GCPET is a sensitive and specific method of detecting metastatic deposits in the axillary lymph nodes of patients with LABC and may obviate or minimize the need for surgery.

Is the uptake of 99mTc sestamibi in breast cancer related to tumour grade

Aim:The aim of this study is to determine whether 99mTc sestamibi (MIBI) uptake in breast cancer is influenced by tumour grade. Method:Sixty-six breast tumours with pathological assessment of tumour grade were scanned using a standard MIBI imaging procedure. Tumour-to-background ratios (TBRs) were calculated using contra-lateral (CL) and peri-tumoural (PT) background ROIs. The Wilcoxon matched pairs signed ranks test was used to determine if TBRs calculated using either technique were statistically different. The non-parametric Mann–Whitney rank sum test was used to determine whether TBRs differed between groups of patients classified by tumour grade. Results:There was a significant difference (P<0.05) between the TBRs obtained using either background ROI. No significant difference (P>0.05) in the TBRs between grades I and II using either technique, or grades II and III using PT ROI, was shown. However, there was a significant difference (P<0.05) in the TBRs between grade I and grade III, calculated using both methods, and grade II and grade III using CL ROIs. Conclusion:The method of background determination and the grade of the tumour, with high grade tumours showing higher uptake, influence the TBR.

The accuracy of 99mTc sestamibi in monitoring the response of locally advanced breast cancer to neoadjuvant chemotherapy

Aim99mTc sestamibi (MIBI) scintimammography is an established technique in the diagnosis of breast cancer. As a functional imaging technique it may offer advantages in assessing response to neoadjuvant chemotherapy. The aim of this study was to assess the techniques effectiveness for this purpose. MethodTwenty-six patients undergoing neoadjuvant chemotherapy for locally advanced breast cancer were monitored during the chemotherapy regime using the tumour to background ratio of MIBI. Patients were assessed clinically and by ultrasound prior to neoadjuvant chemotherapy and at the end of the chemotherapy prior to surgery and histological assessment. The tumour size was assessed each time both by clinical palpation and by ultrasound measurement. ResultsUpon completion of chemotherapy, 4 patients demonstrated uptake of MIBI. All 4 patients had significant residual disease. Three out of the remaining 22 patients had complete pathological response. The remaining 19 patients had residual disease that MIBI failed to demonstrate. ConclusionA positive MIBI scan is highly predictive of the presence of significant residual tumour upon the completion of chemotherapy. However, a negative MIBI scan does not necessarily mean that there is no residual tumour. In fact, considerable tumour may be present. Unlike ultrasound and clinical assessment, which tend to underestimate response to chemotherapy due to the presence of residual scar tissue, MIBI imaging tends to overestimate the response to chemotherapy.