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Similarly, another group reported that patients with primary prostate tumors with high SUVs had a poorer prognosis than did those with low SUVs Moreover, because 18 F-FDG uptake in prostate tumors appears to depend on the presence and activity of androgen, 18 F-FDG PET might also be useful in predicting the time to reach the androgen-refractory state e. Acetate participates in cytoplasmic lipid synthesis, which is believed to be increased in tumors. The cellular retention of radiolabeled acetate in prostate cancer cell lines is primarily due to incorporation of the radiocarbon into phosphatidylcholine and neutral lipids of the cells Recent in vitro and animal model in vivo studies by the group at Washington University in St.
Louis confirmed the extensive involvement of the fatty acid synthesis pathway in 11 C-acetate uptake in prostate tumors as an imaging marker for fatty acid synthase expression Fatty acid synthase is the major enzyme required for converting carbohydrates to fatty acids, and its upregulation plays a role in tumorigenesis of the prostate in the transgenic adenocarcinoma of the mouse prostate model Normal biodistribution of 11 C-acetate demonstrates high accumulation in the pancreas, variable uptake in the liver and bowel, and some renal uptake, with little urinary excretion The lack of accumulation of 11 C-acetate in urine is advantageous to imaging prostate cancer in particular, because the prostate bed remains unobstructed by the adjacent high levels of radioactivity in the urinary bladder, potentially a problem with 18 F-FDG.
Although there can be a considerable overlap between the uptake level in primary cancer, benign prostatic hyperplasia, and the normal prostate gland, tracer uptake generally appears to be greater in the tumor than in normal and benign prostatic hyperplasia tissue Another finding from this study was an age-related physiologic accumulation of 11 C-acetate SUV, 3.
The tumors demonstrated a variable uptake of 11 C-acetate in all 18 patients , with SUVs ranging from 3. The authors concluded that 11 C-acetate is more sensitive than 18 F-FDG in the detection of primary prostate cancer.
In a comparative study with 18 F-FDG, the median 11 C-acetate uptake was higher than 18 F-FDG for local recurrence and regional lymph node metastases whereas the reverse was noted with distant metastases A y-old man with history of prostate cancer who had undergone resection and had rising PSA level. Additional L4 vertebral metastasis is seen on maximum-intensity-projection image A, short arrow.
An 18 F-labeled formulation of acetate which allows commercial regional distribution similar to 18 F-FDG has also been reported to have potential use in prostate cancer A comparative animal study of 11 C-acetate and 18 F-fluoroacetate showed that for most organs except blood, muscle, and fat the tumor-to-organ uptake ratios at 30 min after tracer administration were higher with 18 F-fluoroacetate whereas the tumor-to-heart and tumor-to-prostate ratios were similar A recent investigation in Cynomolgus monkeys and pigs showed that 18 F-fluoroacetate is not a functional analog of 11 C-acetate in normal physiology.
Radiolabeled choline accumulates in prostate tumors Therefore, choline PET has been found to be useful in imaging prostate cancer 48 — The biologic basis for radiolabeled choline uptake in tumors is the malignancy-induced upregulation of choline kinase, which leads to the incorporation and trapping of choline in the form of phosphatidylcholine lecithin in the tumor cell membrane.
Choline uptake in prostate tumors appears not to be correlated with cellular proliferation as depicted by Ki but may be affected by hypoxia 52 , Under aerobic conditions, both androgen-sensitive and androgen-independent prostate tumors have shown higher choline uptake than that with radiolabeled acetate or with 18 F-FDG. However, during hypoxia, the tumor uptake with 18 F-FDG and acetate is higher than that with choline Both 11 C- and 18 F-labeled choline have been synthesized and investigated 54 , Normal biodistribution of 11 C-choline demonstrates relatively high accumulation in the pancreas, liver, kidneys, and salivary glands and variable uptake in the bowel, with little urinary excretion.
These conflicting results may be due to differing methodology in data collection or analysis and in patient populations. Diagnostic validation was by histology, follow-up, or consensus reading. Therefore the 2 imaging modalities were complementary. The authors therefore suggested that reliable clinical decision making e. For example, Scher et al. Martorana et al. Therefore, although 11 C-choline PET may be helpful in detecting primary prostate cancer, the sensitivity may depend on several factors that will need to be defined e.
The tracer uptake was noted to decrease both in the primary tumor and in metastases after hormonal therapy, although this finding has been disputed in other studies 47 , The reason for such a difference based on the type of primary therapy is unclear. In the study by Krause et al. Castellucci et al. The authors found that the likelihood of lesion detection by the nonstandard imaging evaluation with 11 C-choline PET was increased when PSA was higher than 2.
However, this study included some patients with abnormal standard imaging evidence of disease that did not satisfy the pure-definition requirement of PSA relapse-only disease with negative standard imaging results. The PSA range and median were 0. The Gleason score for the primary disease was 2—7 well to moderately differentiated in The authors reported a sensitivity of In summary, despite some mixed results, it appears that the sensitivity of PET may generally depend directly on serum PSA level, with the expectation that at higher PSA levels, the probability of lesion localization increases.
Moreover, 11 C-acetate and 11 C-choline appear to be about equally useful in imaging prostate cancer in individual patients An 18 F-labeled formulation of choline has also been developed and preliminarily tested in men with prostate cancer Fig. Price et al. The exact reason for such an observation is unclear but may be due to the biologic differences between an implanted tumor and a native tumor.
A recent animal study from our group showed that uptake interval and castration do not significantly affect the level of choline uptake in prostate tumors Maximum-intensity-projection image on left shows normal biodistribution of 18 F-fluorocholine and no other suggestive lesions.
Courtesy of Mohsen Beheshti, St. Vincent's Hospital, Linz, Austria. The normal biodistribution of 18 F-fluorocholine demonstrates relatively high accumulation in the pancreas, liver, spleen, and kidneys; variable uptake in the bowel; and excretion into urine. Beheshti et al. Not surprisingly, the diagnostic performance improved when nodes smaller than the PET spatial resolution were excluded.
Another study from the same group of investigators correlated the uptake of 18 F-fluorocholine in bone metastases with the morphologic changes on CT in 70 men with prostate cancer The standard of reference was other imaging and clinical follow-up. No statistically significant difference was found in the maximum SUV of lesions in relation to the presence or absence of hormonal therapy.
Conversely, the bone lesion CT density was significantly higher in patients receiving hormonal therapy. This study revealed that 18 F-fluorocholine might be superior for early detection i. Therefore, metabolic and morphologic changes of bone metastases are dynamic processes, and combined imaging is best suited to capture the natural course of these changes to allow for management decisions and accurate assessment of treatment response.
Biologically and clinically, prostate cancer is a heterogeneous disease that is characterized by states ranging from indolent to aggressive. The use of PET in prostate cancer should be considered in the context of the limitations and challenges associated with other imaging modalities in prostate cancer.
Current evidence indicates that 18 F-FDG PET might be useful in diagnosis and staging of primary tumors that are known or suspected to have a high Gleason score, in detection of metastatic disease in a fraction of men with biochemical failure with scan sensitivity that increases with increasing PSA level, in assessment of the extent of metabolically active castrate-resistant disease, in monitoring response to androgen deprivation and other therapies, and in prognostication.
Both 11 C-acetate and 11 C-choline appear to be somewhat equally useful in imaging prostate cancer in individual patients, although more comparative data are needed. Like 18 F-FDG, choline and acetate cannot differentiate between malignant and benign prostate disease. There are also mixed findings about the effect of androgen deprivation therapy on choline uptake in prostate tumors, probably due to the heterogeneity of androgen receptor function.
It is clear that prospective clinical imaging trials using various PET tracers, singly or in combination, in different clinical-state—specific patient cohorts with well-defined endpoints, will be needed to decipher the optimal use of PET in prostate cancer. Learning Objectives: On successful completion of this activity, participants should be able to describe 1 the potential role of imaging in prostate cancer and 2 the current evidence on the use of 18 F-FDG, 18 F- or 11 C-acetate, and 18 F- or 11 C-choline in the imaging evaluation of prostate cancer.
Financial Disclosure: The authors of this article have indicated no relevant relationships that could be perceived as a real or apparent conflict of interest. Physicians should claim only credit commensurate with the extent of their participation in the activity. Read article at publisher's site DOI : Free to read at jnm. Subscription required at jnm. Cancers Basel , 12 8 , 04 Aug Aroldi F , Lord SR.
Br J Cancer , 1 , 10 Dec Prostate Cancer Prostatic Dis , 23 3 , 13 Jan Cited by: 0 articles PMID: Cancers Basel , 12 1 , 20 Dec To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.
Recent Activity. Recent history Saved searches. Jadvar H 1. Affiliations 1 author 1. Share this article Share with email Share with twitter Share with linkedin Share with facebook. In this article, I review the preclinical and clinical evidence on the potential and emerging role of PET with the 3 most commonly studied radiotracers in prostate cancer, namely 18F-FDG, 18F- or 11C-acetate, and 18F- or 11C-choline.
Free full text. J Nucl Med. Author manuscript; available in PMC Jan 1. PMID: Hossein Jadvar. Author information Copyright and License information Disclaimer. Copyright notice. The publisher's final edited version of this article is available free at J Nucl Med. See other articles in PMC that cite the published article. Go to:.
Molecular Biology Correlates of Tumor Uptake The ability of 18 F-FDG PET to detect cancer is based on elevated glucose metabolism in the malignant tissue in comparison to the normal tissue Warburg effect as a result of increased expression of cellular membrane glucose transporters mainly transporter 1 and enhanced hexokinase II enzymatic activity in tumors 10 , Open in a separate window.
Biochemical Failure and Restaging 18 F-FDG PET may be useful in detecting disease in a fraction of the large proportion of men who present with PSA relapse, in whom, by definition, there is no standard imaging evidence of disease. Therapy Response Assessment In 1 report, 18 F-FDG accumulation in the primary prostate cancer and metastatic sites decreased over a period of 1—5 mo after initiation of androgen deprivation therapy, as was consistent with results from animal xenograft studies Prognostication The level and extent of 18 F-FDG accumulation in metastatic lesions may provide information on prognosis.
Molecular Biology Correlates of Tumor Acetate Uptake Acetate participates in cytoplasmic lipid synthesis, which is believed to be increased in tumors. Primary Tumor and Staging Normal biodistribution of 11 C-acetate demonstrates high accumulation in the pancreas, variable uptake in the liver and bowel, and some renal uptake, with little urinary excretion Biochemical Failure and Restaging 11 C-choline PET has been evaluated for detecting local, regional, and metastatic prostate cancer Kessler B, Albertsen P.
The natural history of prostate cancer. Urol Clin North Am. Prostate cancer: biology of metastasis and its clinical implications. World J Urol. Natural history of progression after PSA elevation following radical prostatectomy. Jenster G. The role of the androgen receptor in the development and progression of prostate cancer.
Semin Oncol. Jadvar H, Alavi A. Role of imaging in prostate cancer. PET Clin. Parasagittal biopsies add minimal information in repeat saturation prostate biopsy. Anticancer Res. Prostate cancer staging with imaging. BJU Int. Molecular and cellular regulation of glucose transport GLUT proteins in cancer.
J Cell Physiol. With this in mind the interpretation of published studies with partial breast irradiation alone becomes more interesting. In this context, dependent on tumour localisation, the ipsilateral axilla levels may receive no or only very little irradiation. Table 3 summarises an analysis of 5 studies on this theme. Among these only the ELIOT study showed a significantly increased regional lymph node recurrence rate One explanation for this is certainly the significantly higher proportion of node-positive cases in the ELIOT.
Nevertheless the axillary recurrence rate of 1. A meta-analysis of three studies, taking 5—8 years of follow-up into account, found no significant increase in axillary recurrence rate following partial breast irradiation alone Thus there is no clear evidence that minimising postoperative radiotherapy of the remaining breast in a low-risk SLNB collective increases the axillary recurrence rate.
It is still unclear whether the concept of avoiding SLNB can also be applied to patients receiving partial breast irradiation alone. With subtyping of breast carcinoma according to hormone receptor HR status, HER2 status, tumour grade and Ki systemic treatment is planned according to the intrinsic tumour subtypes rather than nodal status The year survival rate without distant metastases was Chemotherapy is indicated for the luminal-like subtype when 4 or more lymph nodes are involved Table 4.
Gallen consensus recommendations Of these 11 patients 8 had three, and 1 had 4, 5 and 6 involved nodes respectively so that the proportion of patients with the relevant pN2a tumour stage was only 0. Most guidelines and treatment recommendations regard more than three positive axillary lymph nodes as the only definite indication The current version of the INSEMA protocol amendment 4 has taken this treatment recommendation into account following the full text publication of the MA.
As anticipated there have been no unexpected results from the INSEMA trial after recruitment of the first patients. Acceptance of study participation is high among both patients and doctors. A degree of selection bias at the trial centres before recruitment is probably contributary, high-risk cases being more likely to receive neoadjuvant therapy.
Postoperative treatment decisions with respect to adjuvant systemic and radiotherapy can be made in accordance with guidelines without knowledge of nodal status in almost all cases, based solely on available tumour parameters. Future studies should investigate the avoidance of axillary SLNB in patients with a mastectomy indication and in those with partial breast irradiation alone after breast conserving surgery.
Am Randomisierung rekrutieren. Feinnadelaspiration vom suspekten Lymphknoten notwendig. Multikathetertechnik ; beide Techniken sind als Boost erlaubt. Randomisierung einbringen. Patientin in die Studie eingeschlossen. Der Anspruch auf maximale onkologische Sicherheit seitens der Patientin bzw.
Somit bleibt auch die 2. Zudem wird erwartet, dass die postoperative Strahlentherapie in beiden Studien nicht identisch sein wird. So war in der 5. Die lokale operative Therapie in Form einer kompletten Axilladissektion bei Kapseldurchbruch scheint aber im Zeitalter einer modernen multimodalen Therapie nicht zwingend erforderlich zu sein. Bei den 66 Patientinnen ohne komplette Axilladissektion zeigte sich nach einem medianen Follow-up von 21 Monaten kein einziges Lokalrezidiv Neoplastische Emboli, freie Tumorzellnester im Fettgewebe oder Metastasen im Marginalsinus sollten nicht als relevanter Kapseldurchbruch dokumentiert werden Auch andere Studien z.
In 3 prospektiv randomisierten Studien MA. Mit modernen Bestrahlungstechniken z. Die Auswertung von 5 Studien zu dieser Fragestellung ist in Tab. Anzahl befallener Lymphknoten siehe oben. We thank the patients and trial centres for their participation in the INSEMA trial, see Table 5 for the top 10 recruiting trial centres.
Mrs S. National Center for Biotechnology Information , U. Journal List Geburtshilfe Frauenheilkd v. Geburtshilfe Frauenheilkd. Reimer , A. Stachs , V. Nekljudova , S. Loibl , S. Hartmann , K. Wolter , G. Hildebrandt , and B. Author information Article notes Copyright and License information Disclaimer. This article has been cited by other articles in PMC. Abstract Axillary lymph node status remains an important prognostic factor in early breast cancer. Open in a separate window. ME alone vs. The following changes to recruitment for the second study question of the INSEMA trial are contained in the current protocol amendment 4: Inclusion of patients with one to three macrometastases following SNLB; German trial centres may recruit directly for the second randomisation.
Significance of transcapsular spread in involved lymph nodes The prognostic significance of lymph node capsule infiltration and capsule rupture with extranodal tumour spread is controversial. Deciding on irradiation of the regional lymphatics depending on nodal status Three prospective randomised trials MA. Rate of axillary recurrence in studies using partial breast irradiation alone It is currently assumed that in the context of BCT axillary recurrence is minimised by postoperative whole breast irradiation, even in patients with negative SLNB Deciding on systemic treatment and radiotherapy without knowledge of nodal status With subtyping of breast carcinoma according to hormone receptor HR status, HER2 status, tumour grade and Ki systemic treatment is planned according to the intrinsic tumour subtypes rather than nodal status Chemotherapy regardless of nodal status.
ME allein vs. Notwendigkeit der 2. Acknowledgements We thank the patients and trial centres for their participation in the INSEMA trial, see Table 5 for the top 10 recruiting trial centres. Waldkrankenhaus Spandau Berlin 33 2 Univ. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group Z randomized trial.
Ann Surg. Axillary lymph node dissection in early-stage invasive breast cancer: is it still standard today? Breast Cancer Res Treat. Local treatment of the axilla in early breast cancer: concepts from the national surgical adjuvant breast and bowel project B to the planned intergroup sentinel mamma trial.
Breast Care Basel ; 9 — Physical function of the upper limb after breast cancer surgery. Observation after axillary Ultra-souND trial. Eur J Surg Oncol. Sentinel lymph node biopsy for patients with early-stage breast cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. Long-term follow-up of breast cancer patients with negative sentinel node and no axillary dissection confirms low rate of axillary disease. Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases IBCSG : a phase 3 randomised controlled trial.
Lancet Oncol. Ann Oncol. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: long-term follow-up from the American College of Surgeons Oncology Group Alliance ACOSOG Z randomized trial. Goyal A, Dodwell D. POSNOC: a randomised trial looking at axillary treatment in women with one or two sentinel nodes with macrometastases.
Clin Oncol R Coll Radiol ; 27 — Senomac The value of completion axillary treatment in sentinel node positive breast cancer patients undergoing a mastectomy: a Dutch randomized controlled multicentre trial BOOG BMC Cancer. Ann Surg Oncol. AGO Diagnostic and treatment of early and metastatic breast cancer Axillary dissection vs. Philadelphia, PA: Lippincott-Raven; Extra-nodal extension of sentinel lymph node metastasis is a marker of poor prognosis in breast cancer patients: a systematic review and an exploratory meta-analysis.
Size of extranodal extension on sentinel lymph node dissection in the American College of Surgeons Oncology Group Z trial era. JAMA Surg. The extent of extracapsular extension may influence the need for axillary lymph node dissection in patients with T1-T2 breast cancer.
Incorporation of sentinel lymph node metastasis size into a nomogram predicting nonsentinel lymph node involvement in breast cancer patients with a positive sentinel lymph node. Predicting the extent of nodal disease in early-stage breast cancer. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. Internal mammary and medial supraclavicular irradiation in breast cancer. Ten-year survival results of a randomized trial of irradiation of internal mammary nodes after mastectomy.
DBCG-IMN: a population-based cohort study on the effect of internal mammary node irradiation in early node-positive breast cancer. Adjuvant radiation therapy of regional lymph nodes in breast cancer - a meta-analysis of randomized trials- an update.
Radiat Oncol. No clear effect of postoperative radiotherapy on survival of breast cancer patients with one to three positive nodes: a population-based study.
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