Short-Course or Total Neoadjuvant Chemotherapy in Resectable and Borderline Resectable Pancreatic Cancer - Current Status and Future Perspectives

Labori, Knut Jørgen

doi:10.3389/fsurg.2022.839339

Cited by 6 publications

(6 citation statements)

References 54 publications

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“…The majority of studies on neoadjuvant treatment of pancreatic cancer concentrate on radiographic prediction of resectability or rates of radiographic downstaging rather than attempting to identify possible functional predictors of tumor response (20)(21)(22). There is an absence of effective imaging techniques and serological biomarkers for the assessment of tumor response for neoadjuvant chemotherapy in resectable and borderline resectable pancreatic cancer (23). Gauging the tumor microenvironment (TME) heterogeneities, particularly vasculature and function, i.e., tumor oxygenation status, at high resolution is needed to both evaluate treatment response and predict recurrence at an early phase during treatment (24).…”

Section: Introductionmentioning

confidence: 99%

3D Ultrasound-Guided Photoacoustic Imaging to Monitor the Effects of Suboptimal Tyrosine Kinase Inhibitor Therapy in Pancreatic Tumors

et al. 2022

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Pancreatic cancer is a disease with an incredibly poor survival rate. As only about 20% of patients are eligible for surgical resection, neoadjuvant treatments that can relieve symptoms and shrink tumors for surgical resection become critical. Many forms of treatments rely on increased vulnerability of cancerous cells, but tumors or regions within the tumors that may be hypoxic could be drug resistant. Particularly for neoadjuvant therapies such as the tyrosine kinase inhibitors utilized to shrink tumors, it is critical to monitor changes in vascular function and hypoxia to predict treatment efficacy. Current clinical imaging modalities used to obtain structural and functional information regarding hypoxia or oxygen saturation (StO2) do not provide sufficient depth penetration or require the use of exogenous contrast agents. Recently, ultrasound-guided photoacoustic imaging (US-PAI) has garnered significant popularity, as it can noninvasively provide multiparametric information on tumor vasculature and function without the need for contrast agents. Here, we built upon existing literature on US-PAI and demonstrate the importance of changes in StO2 values to predict treatment response, particularly tumor growth rate, when the outcomes are suboptimal. Specifically, we image xenograft mouse models of pancreatic adenocarcinoma treated with suboptimal doses of a tyrosine kinase inhibitor cabozantinib. We utilize the US-PAI data to develop a multivariate regression model that demonstrates that a therapy-induced reduction in tumor growth rate can be predicted with 100% positive predictive power and a moderate (58.33%) negative predictive power when a combination of pretreatment tumor volume and changes in StO2 values pretreatment and immediately posttreatment was employed. Overall, our study indicates that US-PAI has the potential to provide label-free surrogate imaging biomarkers that can predict tumor growth rate in suboptimal therapy.

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Section: Introductionmentioning

confidence: 99%

3D Ultrasound-Guided Photoacoustic Imaging to Monitor the Effects of Suboptimal Tyrosine Kinase Inhibitor Therapy in Pancreatic Tumors

et al. 2022

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“…Second, we assumed that neoadjuvant treatment would have been a viable alternative in case of a futile up-front pancreatectomy . In this framework, the 6-month time mark corresponds to the immortal time relative to a neoadjuvant therapy course in previous trials and landmark analyses …”

Section: Methodsmentioning

confidence: 99%

Futility of Up-Front Resection for Anatomically Resectable Pancreatic Cancer

Crippa,

Malleo,

Mazzaferro

et al. 2024

JAMA Surg

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ImportanceThere are currently no clinically relevant criteria to predict a futile up-front pancreatectomy in patients with anatomically resectable pancreatic ductal adenocarcinoma.ObjectivesTo develop a futility risk model using a multi-institutional database and provide unified criteria associated with a futility likelihood below a safety threshold of 20%.Design, Setting, and ParticipantsThis retrospective study took place from January 2010 through December 2021 at 5 high- or very high-volume centers in Italy. Data were analyzed during April 2024. Participants included consecutive patients undergoing up-front pancreatectomy at the participating institutions.ExposureStandard management, per existing guidelines.Main Outcomes and MeasuresThe main outcome measure was the rate of futile pancreatectomy, defined as an operation resulting in patient death or disease recurrence within 6 months. Dichotomous criteria were constructed to maintain the futility likelihood below 20%, corresponding to the chance of not receiving postneoadjuvant resection from existing pooled data.ResultsThis study included 1426 patients. The median age was 69 (interquartile range, 62-75) years, 759 patients were male (53.2%), and 1076 had head cancer (75.4%). The rate of adjuvant treatment receipt was 73.7%. For the model construction, the study sample was split into a derivation (n = 885) and a validation cohort (n = 541). The rate of futile pancreatectomy was 18.9% (19.2% in the development and 18.6% in the validation cohort). Preoperative variables associated with futile resection were American Society of Anesthesiologists class (95% CI for coefficients, 0.68-0.87), cancer antigen (CA) 19.9 serum levels (95% CI, for coefficients 0.05-0.75), and tumor size (95% CI for coefficients, 0.28-0.46). Three risk groups associated with an escalating likelihood of futile resection, worse pathological features, and worse outcomes were identified. Four discrete conditions (defined as CA 19.9 levels-adjusted-to-size criteria: tumor size less than 2 cm with CA 19.9 levels less than 1000 U/mL; tumor size less than 3 cm with CA 19.9 levels less than 500 U/mL; tumor size less than 4 cm with CA 19.9 levels less than 150 U/mL; and tumor size less than 5 cm with CA 19.9 levels less than 50 U/mL) were associated with a futility likelihood below 20%. Both disease-free survival and overall survival were significantly longer in patients fulfilling the criteria.Conclusions and relevanceIn this study, a preoperative model (MetroPancreas) and dichotomous criteria to determine the risk of futile pancreatectomy were developed. This might help in selecting patients for up-front resection or neoadjuvant therapy.

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“…While findings from RCTs of adjuvant chemotherapy given to patients receiving upfront surgery have suggested that the ideal time frame for perioperative systemic chemotherapy is 6 mo[ 52 ], there is no agreement on the length and cycle of NAT for BRPC patients. To make this decision, NAT endpoints will need to be defined to assess responsiveness and tumor re-staging during treatment.…”

Section: Nat For Brpcmentioning

confidence: 99%

Comprehensive multimodal management of borderline resectable pancreatic cancer: Current status and progress

H¹,

Li²,

Li³

et al. 2023

World J Gastrointest Surg

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Borderline resectable pancreatic cancer (BRPC) is a complex clinical entity with specific biological features. Criteria for resectability need to be assessed in combination with tumor anatomy and oncology. Neoadjuvant therapy (NAT) for BRPC patients is associated with additional survival benefits. Research is currently focused on exploring the optimal NAT regimen and more reliable ways of assessing response to NAT. More attention to management standards during NAT, including biliary drainage and nutritional support, is needed. Surgery remains the cornerstone of BRPC treatment and multidisciplinary teams can help to evaluate whether patients are suitable for surgery and provide individualized management during the perioperative period, including NAT responsiveness and the selection of surgical timing.

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Short-Course or Total Neoadjuvant Chemotherapy in Resectable and Borderline Resectable Pancreatic Cancer - Current Status and Future Perspectives

Cited by 6 publications

References 54 publications

3D Ultrasound-Guided Photoacoustic Imaging to Monitor the Effects of Suboptimal Tyrosine Kinase Inhibitor Therapy in Pancreatic Tumors

3D Ultrasound-Guided Photoacoustic Imaging to Monitor the Effects of Suboptimal Tyrosine Kinase Inhibitor Therapy in Pancreatic Tumors

Futility of Up-Front Resection for Anatomically Resectable Pancreatic Cancer

Comprehensive multimodal management of borderline resectable pancreatic cancer: Current status and progress

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