TO THE EDITOR: 

We read and re-read your outstanding supplement titled “A Tabulated Summary of the FDG PET Literature” ([1][1]). It helps take the world literature and put it in perspective. This has already helped us discuss the pros and cons of PET imaging in pancreatic carcinoma with a

https://jnm.snmjournals.org/content/jnumed/42/5_suppl/1S.full.pdf

A Tabulated Summary of the FDG PET Literature

Positron emission tomography (PET) provides metabolic information that has been documented to be useful in patient care. The properties of positron decay permit accurate imaging of the distribution of positron-emitting radiopharmaceuticals. The wide array of positron-emitting radiopharmaceuticals has been used to characterize multiple physiologic and pathologic states. PET is used for characterizing brain disorders such as Alzheimer disease and epilepsy and cardiac disorders such as coronary artery disease and myocardial viability. The neurologic and cardiac applications of PET are not covered in this review. The major utilization of PET clinically is in oncology and consists of imaging the distribution of fluorine 18 fluorodeoxyglucose (FDG). FDG, an analogue of glucose, accumulates in most tumors in a greater amount than it does in normal tissue. FDG PET is being used in diagnosis and follow-up of several malignancies, and the list of articles supporting its use continues to grow. In this review, the ph...

Clinical Applications of PET in Oncology

2-[(18)F]Fluoro-2-deoxyglucose positron emission tomography (FDG-PET) assesses a fundamental property of neoplasia, the Warburg effect. This molecular imaging technique offers a complementary approach to anatomic imaging that is more sensitive and specific in certain cancers. FDG-PET has been widely applied in oncology primarily as a staging and restaging tool that can guide patient care. However, because it accurately detects recurrent or residual disease, FDG-PET also has significant potential for assessing therapy response. In this regard, it can improve patient management by identifying responders early, before tumor size is reduced; nonresponders could discontinue futile therapy. Moreover, a reduction in the FDG-PET signal within days or weeks of initiating therapy (e.g., in lymphoma, non-small cell lung, and esophageal cancer) significantly correlates with prolonged survival and other clinical end points now used in drug approvals. These findings suggest that FDG-PET could facilitate drug development as an early surrogate of clinical benefit. This article reviews the scientific basis of FDG-PET and its development and application as a valuable oncology imaging tool. Its potential to facilitate drug development in seven oncologic settings (lung, lymphoma, breast, prostate, sarcoma, colorectal, and ovary) is addressed. Recommendations include initial validation against approved therapies, retrospective analyses to define the magnitude of change indicative of response, further prospective validation as a surrogate of clinical benefit, and application as a phase II/III trial end point to accelerate evaluation and approval of novel regimens and therapies.

https://clincancerres.aacrjournals.org/content/clincanres/11/8/2785.full.pdf

Progress and Promise of FDG-PET Imaging for Cancer Patient Management and Oncologic Drug Development

PURPOSE: To perform a meta-analysis to compare current noninvasive imaging methods (ultrasonography [US], computed tomography [CT], magnetic resonance [MR] imaging, and 18F fluorodeoxyglucose [FDG] positron emission tomography [PET]) in the detection of hepatic metastases from colorectal, gastric, and esophageal cancers. MATERIALS AND METHODS: A MEDLINE literature search and review of article bibliographies and our institutional charts of patients with colorectal cancer identified data with histopathologic correlation or at least 6 months of patient follow-up. Two authors independently abstracted data sets and excluded data without contingency tables or data published more than once. Summary-weighted estimates of sensitivity were obtained and stratified according to specificity of less than 85% or 85% and higher. A covariate analysis was used to evaluate the influence of patient- or study-related factors on sensitivity. RESULTS: Among 111 data sets, nine US (509 patients), 25 CT (1,747 patients), 11 MR im...

Detection of Hepatic Metastases from Cancers of the Gastrointestinal Tract by Using Noninvasive Imaging Methods (US, CT, MR Imaging, PET): A Meta-Analysis

Role of chemokines in tumor growth

https://www.annalsthoracicsurgery.org/article/S0003-4975(05)01559-6/pdf

Nonoperative treatment of 15 benign esophageal perforations with self-expandable covered metal stents.

Diagnostic imaging for suspected tumour recurrence of primary colorectal cancer frequently lacks specificity and sensitivity. The impact of whole body 18F-FDG-positron-emission tomography (PET) on detection of local recurrences and hepatic or pulmonary metastases was evaluated in a prospective study. Results were compared with computed tomography (CT), ultrasonography, magnetic resonance imaging and conventional chest X-ray. The study included 71 patients (77 investigations) with suspected local recurrence, hepatic metastases or unexplained raised level of the tumour marker carcinoembryonic antigen (CEA). The results demonstrate that 18F-FDG-PET was clearly superior to CT with regard to detection of hepatic metastases. Sensitivity was 1.0 and specificity 0.98 compared with 0.87 and 0.91 for CT. In four cases, 18F-FDG-PET clarified otherwise unclear local recurrences. In five patients, 18F-FDG-PET showed pulmonary metastases that had previously been unknown. In a total of 16 patients (20.8%), 18F-FDG-PET provided additional information leading to a change of the treatment strategy. 18F-FDG-PET clearly has the ability to detect colorectal tumour recurrence and its metastases in a whole body format. Therefore, it may be applied in the follow-up of patients with primary colorectal cancer. Despite the costs, it is certainly recommended for patients with an otherwise unclear increase of CEA level or with unproven local recurrence.

Impact of 18F-FDG-positron emission tomography for decision making in colorectal cancer recurrences.

Background: Chemokines (CKs) may promote antitumor immunity in cancer, act as tumor growth factors, influence metastatic spreading or angiogenesis. The purpose of this study was to investigate whether CK expression is altered in colorectal carcinomas compared to normal mucosa and to elucidate its possible clinico-pathological implications. Materials and Methods: The levels of CCL2 (MCP-1), CCL 4 (MIP-1‚), CCL5 (RANTES), CXCL 1 (GRO-·), CXCL 5 (ENA-78) and CXCL8 (IL-8) were investigated in 10 colorectal carcinomas and their corresponding normal mucosa by the use of ELISA. Results: All CK analyzed, with the exception of CCL5 (RANTES), were expressed at a significantly higher level in malignant tissue. Conclusion: Therapeutic studies in colon carcinomas should, therefore, focus more on the neutralization of CKs than on their application. Chemokines (CKs) are small (8-11kDa), secreted proteins

Chemokines in Human Colorectal Carcinoma

Surgical site infections (SSI) cause excess morbidity and mortality in modern surgery. Several different approaches to reduce the incidence of SSI have been investigated with variable results. This is to our knowledge the first systematic randomized evaluation in patients undergoing laparotomy in visceral surgery to clarify whether widely used subcutaneous drains (Redon) affect wound infection as the primary outcome measure. In 200 patients, we were unable to show a statistically significant impact on the postoperative healing process in patients with the full variety of abdominal surgical interventions. Overall, we observed surgical site infection in 9.5% of all patients (n = 19), of these n = 9 (47.4%) were in the control group without a drain, and 10 (52.6%) were in the experimental group with a Redon drain (not significant). As this study could not demonstrate a reduction of SSI by the use of Redon drains, there is no indication for prophylactic subcutaneous suction drains after laparotomy.

Subcutaneous Redon drains do not reduce the incidence of surgical site infections after laparotomy. A randomized controlled trial on 200 patients

Background: Cytokines reflect the activity of the immune system. We analyzed the local expression of characteristic cytokines indicating the level of activity of unspecific inflammatory cells, Th1-cells and Th2-cells in colon cancer. Materials and Methods: In 25 tumor/ mucosa pairs, IL-1·, IL-2, IL-4, IL-5, IL-15, TNF-· and IFN-A were measured by real-time PCR. Results: There was a significant increase in IL-1·, IL-4, IL-5 and TNF-· and a significant decrease in IL-2 in tumor tissue compared to normal mucosa. Discussion: The cytokine profile in colon cancer indicates a strong unspecific inflammatory reaction in the tumor tissue represented by high levels of IL-1 and TNF-·. The comparatively low level of IL-2 suggests suppression of a specific immunological reaction, namely Th1-cells. It can be hypothesized that this is a result and/or cause of local immune escape mechanisms. Furthermore, there is an activation of TH2 cells in the carcinomas. Cancer cells express antigens to which the immune system responds with a cytotoxic T lymphocyte (CTL) infiltration and with a delayed type hypersensitivity (DTH) reaction (1, 2); the same holds true in colorectal cancer cells (3). The immune system controls the development of malignancies. If affected, the incidence of malignancies rises, as can be observed in immunosuppressed patients after organ transplantation. The development of a clinically manifest carcinoma implies that immunological control has been insufficient. In this context, many possible systemic and local immune escape mechanisms are being discussed (1, 4). To determine the activity of unspecific immunity, Th1-cells and Th2-cells and possible immune escape mechanisms in colon cancer, we analyzed the expression of various cytokines involved in the activation and differentiation of macrophages and T lymphocytes (5). We compared the level of expression of IL-1·, IL-2, IL-4, IL-5, IL-15, TNF-· and IFN-A in colon carcinoma tissue to normal colon mucosa by real-time PCR in 25 sample pairs. PCR analysis of cytokine expression provides a highly sensitive means of quantifying the antigen-specific immune response(6, 7). As an internal control, we analyzed the expression of FAS-ligand, well known to be expressed more strongly in carcinoma cells than in mucosa (8).

Peter Baier

Papers

Nonoperative treatment of 15 benign esophageal perforations with self-expandable covered metal stents.

Impact of 18F-FDG-positron emission tomography for decision making in colorectal cancer recurrences.

Chemokines in Human Colorectal Carcinoma

Subcutaneous Redon drains do not reduce the incidence of surgical site infections after laparotomy. A randomized controlled trial on 200 patients

Cytokine expression in colon carcinoma.