scholarly journals Overview and Future Perspectives on Tumor-Targeted Positron Emission Tomography and Fluorescence Imaging of Pancreatic Cancer in the Era of Neoadjuvant Therapy

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6088
Author(s):  
Martijn A. van Dam ◽  
Floris A. Vuijk ◽  
Judith A. Stibbe ◽  
Ruben D. Houvast ◽  
Saskia A. C. Luelmo ◽  
...  

Background: Despite recent advances in the multimodal treatment of pancreatic ductal adenocarcinoma (PDAC), overall survival remains poor with a 5-year cumulative survival of approximately 10%. Neoadjuvant (chemo- and/or radio-) therapy is increasingly incorporated in treatment strategies for patients with (borderline) resectable and locally advanced disease. Neoadjuvant therapy aims to improve radical resection rates by reducing tumor mass and (partial) encasement of important vascular structures, as well as eradicating occult micrometastases. Results from recent multicenter clinical trials evaluating this approach demonstrate prolonged survival and increased complete surgical resection rates (R0). Currently, tumor response to neoadjuvant therapy is monitored using computed tomography (CT) following the RECIST 1.1 criteria. Accurate assessment of neoadjuvant treatment response and tumor resectability is considered a major challenge, as current conventional imaging modalities provide limited accuracy and specificity for discrimination between necrosis, fibrosis, and remaining vital tumor tissue. As a consequence, resections with tumor-positive margins and subsequent early locoregional tumor recurrences are observed in a substantial number of patients following surgical resection with curative intent. Of these patients, up to 80% are diagnosed with recurrent disease after a median disease-free interval of merely 8 months. These numbers underline the urgent need to improve imaging modalities for more accurate assessment of therapy response and subsequent re-staging of disease, thereby aiming to optimize individual patient’s treatment strategy. In cases of curative intent resection, additional intra-operative real-time guidance could aid surgeons during complex procedures and potentially reduce the rate of incomplete resections and early (locoregional) tumor recurrences. In recent years intraoperative imaging in cancer has made a shift towards tumor-specific molecular targeting. Several important molecular targets have been identified that show overexpression in PDAC, for example: CA19.9, CEA, EGFR, VEGFR/VEGF-A, uPA/uPAR, and various integrins. Tumor-targeted PET/CT combined with intraoperative fluorescence imaging, could provide valuable information for tumor detection and staging, therapy response evaluation with re-staging of disease and intraoperative guidance during surgical resection of PDAC. Methods: A literature search in the PubMed database and (inter)national trial registers was conducted, focusing on studies published over the last 15 years. Data and information of eligible articles regarding PET/CT as well as fluorescence imaging in PDAC were reviewed. Areas covered: This review covers the current strategies, obstacles, challenges, and developments in targeted tumor imaging, focusing on the feasibility and value of PET/CT and fluorescence imaging for integration in the work-up and treatment of PDAC. An overview is given of identified targets and their characteristics, as well as the available literature of conducted and ongoing clinical and preclinical trials evaluating PDAC-targeted nuclear and fluorescent tracers.

Author(s):  
Laura Evangelista ◽  
Pietro Zucchetta ◽  
Lucia Moletta ◽  
Simone Serafini ◽  
Gianluca Cassarino ◽  
...  

AbstractThe aim of the present systematic review is to examine the role of fluorodeoxyglucose (FDG) positron emission tomography (PET) associated with computed tomography (CT) or magnetic resonance imaging (MRI) in assessing response to preoperative chemotherapy or chemoradiotherapy (CRT) for patients with borderline and resectable pancreatic ductal adenocarcinoma (PDAC). Three researchers ran a database query in PubMed, Web of Science and EMBASE. The total number of patients considered was 488. The most often used parameters of response to therapy were the reductions in the maximum standardized uptake value (SUVmax) or the peak standardized uptake lean mass (SULpeak). Patients whose SUVs were higher at the baseline (before CRT) were associated with a better response to therapy and a better overall survival. SUVs remaining high after neoadjuvant therapy correlated with a poor prognosis. Available data indicate that FDG PET/CT or PET/MRI can be useful for predicting and assessing response to CRT in patients with resectable or borderline PDAC.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5404-5404
Author(s):  
Katie Guo ◽  
Melissa Boileau ◽  
Bernard Fortin ◽  
Francine Aubin ◽  
Tony Petrella ◽  
...  

Abstract Introduction Primary bone lymphoma (PBL) is an uncommon form of lymphoma. Diffuse large B-cell lymphoma (DLBCL) represents the main histology associated with PBL. Clinicopathological understanding and management of PBL rely only on retrospective series. Methods Cases of DLBCL diagnosed by bone biopsy treated in one referring center between 1993 and 2014 were retrospectively reviewed (Montreal, Canada). Bone biopsies done as part of the bone marrow analysis were excluded. Patients files were analyzed to determine if patient had primary bone lymphoma or systemic lymphoma with bony involvement. We excluded patient with distant lymph node or other extranodal involvement. Data on clinical presentation, staging procedures and treatment management including use of radiotherapy was collected. Staging was performed according to WHO classification of soft tissue tumors (2002). Survival time and time to recurrence were calculated from the date of the first documented treatment until recurrence or death with the Kaplan-Meier method. Prognostic factors of recurrence or death were explored with log-rank tests and Cox proportional hazards models. Competing risks analysis was attempted to isolate deaths from lymphoma and death from other causes. Our study was approved by local research and ethic committees. Results We retrieved 42 cases of PBL with a median age of 63 years (23-83) treated between October 1995 and April 2014. We identified 3/14 (21%) GCB and 11/14 (79%) non-GCB subtypes based on the modified Hans algorithm (Meyer et al., JCO 2011). The most common presenting symptom was pain (88%). 12/42 (33%) patients had an IPI score ≥ 3. We identified 18 (43%) stage I, 11 (26%) stage II and 13 (31%) stage IV. 20/42 (48%) had bulky disease (≥ 10cm). Among the 37 patients treated with curative intent, 36 (97%) received CHOP-based regimen and 23 (62%) received rituximab. 30 of these 37 (81%) patients received additional radiotherapy of which 67% received a dose of radiotherapy between 36-50 Gy. Overall response rate for patients treated with curative intent was 86%. With a median follow up of 64.8 months for the whole cohort, the 5- and 10-year overall survival was 73% and 54%, respectively. The 5- and 10-year progression-free survival was 70% and 49% respectively. Age, LDH, stage (I-II vs IV), ECOG (0-1 vs 2-4), IPI (0-2 vs 3-5), use of radiotherapy or addition of rituximab were associated with differences in survival and progression rates that did not reach statistical significance given the limited number of patients in our cohort and the fact that half of the deaths were attributed to other causes. A larger cohort would be required to demonstrate a benefit with rituximab. Response was based on positron emission tomography-computed tomography (TEP-CT) imaging in 12 patients. There was an insufficient number of patients to evaluate the role of adding radiotherapy in patient complete remission defined by PET-CT. Conclusion Our survival rates reproduce published data from series of PBL (Ramadan et al., Ann Oncol 2007; Bruno Ventre et al., Oncologist 2014), although the benefit of adding rituximab did not reach statistical significance in our cohort. The role of radiotherapy in the era of response defined by PET-CT remains to be defined. Disclosures Fleury: Gilead: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Lundbeck: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Speakers Bureau.


2003 ◽  
Vol 92 (1) ◽  
pp. 90-96 ◽  
Author(s):  
C. Penna ◽  
B. Nordlinger

Over the last 30 years, the benefits of surgical resection for liver metastases have been established. Actually, surgical resections are feasible with a very low mortality and 5-year survival that approaches 40 %. However, even if progresses in surgery and anaesthesiology now render possible extensive resections with removal of large, numerous or bilateral lesions, only 10 to 20 % of patients are candidate to surgery. The others gain benefit from chemotherapy with more and more active drugs. To improve this overall picture, efforts have been made to increase the number of patients that could be candidates for surgery. Shrinkage of tumours after administration of preoperative chemotherapy and availability of ablative techniques now permit to treat with curative intent metastases initially considered as non-resectable.


2018 ◽  
Vol 25 (1) ◽  
pp. 107327481774462 ◽  
Author(s):  
Sonia T. Orcutt ◽  
Daniel A. Anaya

Primary liver cancer—including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC)—incidence is increasing and is an important source of cancer-related mortality worldwide. Management of these cancers, even when localized, is challenging due to the association with underlying liver disease and the complex anatomy of the liver. Although for ICC, surgical resection provides the only potential cure, for HCC, the risks and benefits of the multiple curative intent options must be considered to individualize treatment based upon tumor factors, baseline liver function, and the functional status of the patient. The principles of surgical resection for both HCC and ICC include margin-negative resections with preservation of adequate function of the residual liver. As the safety of surgical resection has improved in recent years, the role of liver resection for HCC has expanded to include selected patients with preserved liver function and small tumors (ablation as an alternative), tumors within Milan criteria (transplant as an alternative), and patients with large (>5 cm) and giant (>10 cm) HCC or with poor prognostic features (for whom surgery is infrequently offered) due to a survival benefit with resection for selected patients. An important surgical consideration specifically for ICC includes the high risk of nodal metastasis, for which portal lymphadenectomy is recommended at the time of hepatectomy for staging. For both diseases, onco-surgical strategies including portal vein embolization and parenchymal-sparing resections have increased the number of patients eligible for curative liver resection by improving patient outcomes. Multidisciplinary evaluation is critical in the management of patients with primary liver cancer to provide and coordinate the best treatments possible for these patients.


2021 ◽  
Vol 108 (Supplement_9) ◽  
Author(s):  
Lauren Laverty ◽  
Stephen McCain ◽  
Lloyd McKie

Abstract Background Diagnosis and staging has proven to be difficult in 10-20% of patients with pancreatic cancer. The PET-PANC study found that PET-CT significantly influenced the staging and management of pancreatic cancer and therefore the NICE guidelines now advise PET-CT in all patients who have localised potentially resectable disease. This study aimed to investigate the impact of PET-CT on the management of pancreatic cancer patients in a single tertiary referral centre. Methods There were 288 patients with pancreatic cancer discussed at the Northern Ireland Regional Hepatobiliary MDM from January 2020 to March 2021. Of these patients, 176 were deemed to have inoperable disease based on initial CT, 5 had borderline resectable disease, 1 had holding chemotherapy due to COVID restrictions and 57 were excluded from surgical resection for a variety of reasons. These included the patient being unfit for surgery, the patient declining operative intervention and an alternative treatment offered as result of COVID-19 pandemic. Therefore, there were 49 patients with pancreatic adenocarcinoma which the MDT concluded should be considered for surgical resection. Results A total of 27 patients who were due to undergo a curative resection had a pre-operative PET-CT scan (55.1%). This demonstrated metastatic disease in 9 cases (33.3%). Four patients who did not have a preoperative PET-CT were found to have metastatic disease at operation (9.7%). This equated to a total metastatic incidence of 26.5% in those who had been initially deemed resectable based on CT scan alone. The time interval from MDM decision to surgery averaged 25.4 days in those who did not have a PET/CT compared to 40.43 days in those who did. This was an average delay of 15.07 days until treatment. Conclusions This study demonstrates the important role the PET-CT has in the management of patients with pancreatic cancer. A significant number of patients avoided an unnecessary operation which would have delayed the commencement of chemotherapy. However, there are limitations to PET-CT, demonstrated in the patient with an inconclusive result, who was found to have liver metastases at surgery. The introduction of PET-CT in the staging process does undoubtedly cause delays to surgical resection and a more streamlined pathway needs to be developed to limit the delay to curative treatment.


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 357-357
Author(s):  
Mohamad Osama Khawandanah ◽  
Carla Kurkjian ◽  
Shyla Penaroza ◽  
Charles Arnold ◽  
Terence S. Herman ◽  
...  

357 Background: The standard imaging approach in patients with pancreatic cancer is contrast enhanced computed tomography (CT), however, Response Evaluation Criteria in Solid Tumors (RECIST) may not be adequate in evaluating response to neoadjuvant therapy. A growing body of evidence exists to suggest that there is additional useful information to be gained from the use of FDG-PET scans in this setting. Methods: We conducted an IRB approved retrospective chart review of patients with locally advanced or borderline resectable pancreatic adenocarcinoma who underwent neoadjuvant therapy at the University of Oklahoma and who had PET/CT imaging before and/or after neoadjuvant therapy between September 2006 and September 2013. Complete remission (CR) was defined as decrease in SUV to ≤ 3.0 or background, and partial response (PR) was defined as decrease in SUV from baseline, but > 3.0. Results: A total of 13 patients underwent Whipple surgery after neoadjuvant therapy at our institution. Four patients (31%) had persistent unresectable disease on CT scans post-neoadjuvant therapy, but demonstrated CR (three patients) or PR (one patient; Pre-treatment SUV: 10.1, Post Treatment: 4.6) on the PET scan. These patients underwent Whipple surgery based on PET response. All four (100%) patients underwent R0 resection. Two patients (50%) received neoadjuvant chemo-radiation in addition to chemotherapy. Conclusions: Response on FDG-PET/CT can be a predictor of R0 resection in cases with evidence of unresectable disease on conventional CT scan. A protocol to study larger number of patients prospectively is being designed.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 529-529
Author(s):  
Takayuki Kondo ◽  
Koji Okabayashi ◽  
Hirotoshi Hasegawa ◽  
Masashi Tsuruta ◽  
Ryo Seishima ◽  
...  

529 Background: Non-alcoholic steatohepatitis (NASH) is closely associated with hepatic fibrosis (HF). The number of patients who have NASH is increasing by eating high-calorie diet. It remains unclear how much impact such NASH and HF on the development of liver metastasis by colorectal cancer (CRC). The objectives of this study is to clarify the influence of HF on metachronous liver-specific recurrence in colorectal cancer patients who underwent colorectal surgery with curative intent. Methods: Between 2000 and 2010, patients who underwent a curative surgical resection for CRC were included in this study. We evaluated the progression of HF by using non-alcoholic fatty liver disease fibrosis score (NFS) based on preoperative blood test result, age, BMI and DM. The patients with NFS higher than 0.676 were objectively defined as HF. The influence of HF on hepatic recurrence was assessed by survival analyses. Results: A total of 953 CRC patients were enrolled, comprised of 293 in stage I, 327 in stage II and 333 in stage III. The mean of NFS was 1.32±1.55, where the included patients were categorized into 77 HF and 876 non-HF. 5-year liver-specific disease-free survival rate in HF was significantly poorer than non-HF (HS 87.0% vs. non-HF 94.5%, log-rank p=0.009). Multivariate analysis demonstrated that HF significantly promoted liver-specific recurrence compared to non-HF (HR=2.16, 95% CI, 1.00 to 4.64; p=0.049). Conclusions: Hepatic fibrosis had a great impact on hepatic recurrence after curative surgical resection of CRCs. These findings indicated that HF might be a favorable microenvironment in developing colorectal liver metastasis. The evaluation of the degree of HF can be useful in selection of adjuvant chemotherapy and postoperative surveillance.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 453-453
Author(s):  
Eric Albert Mellon ◽  
Sarah E. Hoffe ◽  
Jessica M. Frakes ◽  
Tobin Joel Crill Strom ◽  
Gregory M. Springett ◽  
...  

453 Background: Neoadjuvant therapy response correlates with survival in several gastrointestinal malignancies. Thus, we intensified our neoadjuvant approach to pancreas adenocarcinoma in part to induce greater response. Here we analyzed whether pre- and post- therapy CA19-9 or SUVmax correlated with College of American Pathology TRG at pancreatectomy and whether TRG associated with survival. Methods: After IRB approval, we identified BRPC and LAPC patients treated in our standardized pathway who underwent surgical resection with reported TRG (n = 81, median follow-up 30.8 months). Patients had baseline CA19-9, CT, endoscopic ultrasound, and FDG PET/CT then underwent multi-agent chemotherapy (79% with planned 3 cycles of GTX) followed by 5 fraction SBRT. They then underwent restaging CT, PET/CT, and CA19-9 prior to resection. Overall (OS) and progression free survival (PFS) were estimated and compared by Kaplan-Meier and log-rank methods. Univariate ordinal logistic regression correlated TRG with baseline, re-staging, and change in CA19-9 (16% with missing values or CA19-9 < 5 excluded) and SUVmax (14% with missing values or no hypermetabolism excluded). Results: Decrease in CA19-9 before and after neoadjuvant therapy correlated with improved TRG (p = 0.02) as did re-staging SUVmax (p < 0.01), though not decrease in SUVmax (p = 0.08). The TRG groupings had similar OS and PFS except the TRG 0 (complete response) group. Compared to TRG 1-3 patients (median OS 38.4 months, median PFS 17.8 months), the 6 patients with TRG 0 had no deaths (p = 0.05) and only 1 failure (p = 0.03). A group of 10 TRG 1 patients with only isolated tumor cells remaining had similar outcomes to the other TRG 1-3 patients. Conclusions: Pre-operative PET-CT and CA19-9 response correlate with neoadjuvant therapy response by TRG. Patients with complete pathologic response have superior outcomes. This provides rationale for further intensification of neoadjuvant therapy in BRPC and LAPC. Further work seeks to identify techniques to better select which BRPC and LAPC patients should undergo tumor resection.


2018 ◽  
Vol 84 (10) ◽  
pp. 1589-1594
Author(s):  
Ahmed Dehal ◽  
Amanda N. Graff-Baker ◽  
Brooke Vuong ◽  
Daniel Nelson ◽  
Shu-Ching Chang ◽  
...  

Accurate preoperative clinical staging is essential to optimize the treatment of rectal cancer. Primary surgical resection is typically indicated for stage I disease, whereas neoadjuvant therapy is recommended for stages II and III. The objective of this study is to examine the accuracy of clinical staging using current imaging modalities in predicting pathologic stage and, thus, selecting appropriate treatment. Adult patients with nonmetastatic rectal cancer who underwent primary surgical resection were identified from the National Cancer Database between 2006 and 2014. Data on clinical and pathologic staging was obtained. Kappa index was used to determine the correlation between clinical and pathologic staging. A total of 13,175 patients were identified. The correlation between clinical and pathologic staging was 69 per cent for stage I (31% upstaged) (Kappa 0.54, P < 0.001). One-third of patients who were clinically staged as stage I, and were therefore treated with primary surgical resection, had pathologic stage II or III disease. Based on their clinical staging, those patients did not receive the neoadjuvant therapy recommended by present guidelines. Where accurate clinical staging is in doubt, oncologists should carefully examine the quality of staging modality and perhaps consider multimodal imaging using both endorectal ultrasound and MRI.


2019 ◽  
Vol 32 (Supplement_2) ◽  
Author(s):  
D J J M de Gouw ◽  
B R Klarenbeek ◽  
M Dressen ◽  
S A W Bouwense ◽  
F van Workum ◽  
...  

Abstract Background Up to 32% of patients with esophageal cancer show a pathological complete response (ypCR) after neoadjuvant therapy. To prevent overtreatment, the indication to perform esophagectomy in these patients should be reconsidered. Implementing an organ-preserving strategy for patients with ypCR requires an accurate assessment of residual disease after neoadjuvant treatment. The aim of this study was to systematically review the effectiveness of imaging techniques used for detection of ypCR after neoadjuvant therapy but before resection in patients with esophageal cancer. Methods A systematic literature search of the Medline, Embase, and Cochrane Library databases was performed from January 1, 2000, to December 13, 2017. Eligible studies were diagnostic studies that compared results of imaging modalities after neoadjuvant therapy to histopathological findings in the resection specimen after esophagectomy. Methodological quality was assessed by the Cochrane Quality Assessment of Diagnostic Accuracy Studies, version 2, model. Primary outcome measures were true positive, false positive, false negative, and true negative values of imaging techniques predicting ypCR. A meta-analysis was performed by pooling sensitivities and specificities by using a bivariate model. Results A total of 4420 articles were identified. After exclusion of irrelevant titles and abstracts, 360 articles were reviewed in full text. In total, four imaging modalities (computed tomography [CT], positron emission tomography [PET-CT], endoscopic ultrasound [EUS], and magnetic resonance imaging [MRI]) were used for restaging. The meta-analysis was conducted with data from 56 studies involving 3625 patients. The pooled sensitivities of CT, PET-CT, EUS, and MRI for detecting ypCR were 0.35, 0.62, 0.01 and 0.80, respectively, whereas the pooled specificities were 0.83, 0.73, 0.99, and 0.83, respectively. The positive predictive value in detecting ypCR was 0.47 for CT, 0.41 for PET-CT, not applicable for EUS, and 0.61 for MRI. Conclusions Current imaging modalities such as CT, PET-CT, and EUS seem to be insufficiently accurate to identify complete responders. More accurate diagnostic tests are needed to improve restaging accuracy for patients with esophageal cancer.


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