(S037) Changes in Mass Transport as an Early Marker of Response to Cytotoxic Therapy in Human Pancreatic Adenocarcinoma

Publication
Article
OncologyOncology Vol 28 No 4_Suppl_1
Volume 28
Issue 4_Suppl_1

One clinical observation is that a decrease in tumor enhancement on CT scans after cytotoxic therapy is generally regarded as a good response. We hypothesized that measuring this phenomenon would correlate with local control of human pancreatic adenocarcinoma (PDAC).

Eugene J. Koay, MD, PhD, Vittorio Cristini, PhD, Priya Bhosale, MD, Mauro Ferrari, PhD, Jason B. Fleming, MD, Christopher Crane, MD; UT MD Anderson Cancer Center; Houston Methodist Research Institute

Background: Identifying a biomarker of local tumor response in pancreatic cancer has proven elusive, because the disease is usually unresectable, which limits the use of pathological response as a readout and because blood-based biomarkers, such as CA19-9, are not necessarily specific to local tumor control. One clinical observation is that a decrease in tumor enhancement on CT scans after cytotoxic therapy is generally regarded as a good response. We hypothesized that measuring this phenomenon would correlate with local control of human pancreatic adenocarcinoma (PDAC).

Methods: We developed an imaging-based biomarker using principles of mass transport. Using systematic measurements of density of pancreatic tissues at each of the timed phases of contrast-enhanced pancreatic protocol CT scans, we applied a mathematical model to derive a mass transport parameter that quantified the area under the enhancement curve (AUC) for patients with PDAC. We defined a “normalized AUC ratio” as the post-therapy AUC (4–8 weeks after treatment) divided by the pre-therapy AUC. This parameter was correlated with clinical outcome in patients treated on two prospective trials. The first trial originally included 48 patients with locally advanced PDAC treated with radiation to 50.4 Gy with concurrent bevacizumab and capecitabine. The second trial originally included 69 patients with locally advanced PDAC treated with induction cetuximab, gemcitabine, and oxaliplatin, followed by radiation to 50.4 Gy with concurrent cetuximab and capecitabine. A total of 84 patients (36 from Trial 1 and 48 from Trial 2) had both post-therapy and pre-therapy pancreatic protocol CT scans to analyze. The others did not have pancreatic protocol CT scans for one or either of the tests.

Results: There were 30 patients with clinical and radiographic evidence of local progression. The 2-year local control rate was 50% for all patients. We found that the normalized AUC ratio correlated significantly with local progression-free survival (PFS) (hazard ratio [HR] = 1.81; 95% confidence interval [CI], 1.01–3.03; P = .048). Furthermore, patients with a measureable decrease in tumor mass transport (normalized AUC ratio < 1) after chemoradiation had significantly better local control (86% with tumor control at 2 years) compared with those without a decrease in tumor mass transport (normalized AUC ratio ≥ 1; 34% with tumor control at 2 years; P = .002). As a continuous or discrete variable (with a cutoff of 1), the normalized AUC ratio correlated with local PFS, independent of therapy regimen, change in tumor size after therapy, and receipt of curative-intent surgery.

Conclusions: After cytotoxic therapies, decreased enhancement in human PDAC tumors correlated with improved local control. This phenomenon can be quantified using our systematic methodology and mathematical model. With further validation, this method may serve as an early readout of response to new therapies, which could help accelerate promising treatments and enable rational management decisions. Ongoing work will address the hypothesis that a decrease in tumor enhancement correlates with pathological response for patients who have resectable PDAC and receive neoadjuvant cytotoxic therapy.

Proceedings of the 96th Annual Meeting of the American Radium Society - americanradiumsociety.org

Articles in this issue

(S002) Outcomes and Prognostic Factors of Stereotactic Body Radiotherapy for Soft Tissue Sarcoma Metastases
(S001) Limb-Sparing Surgery and Intraoperative Radiotherapy in the Treatment of Primary, Nonmetastatic Extremity and Limb-Girdle Soft Tissue Sarcoma
(S003) Disparities in Stage at Diagnosis and Survival in Adult Cancer Patients According to Insurance Status
(S004) Radiation Publications Underrepresented in High-Impact General Medical and Oncology Journals 
(S005) Adjuvant Radiotherapy in Stage II Endometrial Carcinoma: Is Brachytherapy Alone Sufficient for Local Control?
(S006) Extended-Field IMRT With Concomitant Boost for Node-Positive Cervical Cancer: Analysis of Regional Control Rate and Recurrence Pattern
(S007) Stereotactic Radiosurgery to the Brain With Concurrent BRAF Inhibitors for Melanoma Metastases
(S008) Use of Mobile Devices for Creation of Survivorship Care Plans
(S009) Two-Year Outcomes Following Triapine Radiochemotherapy for Cervical Cancer 
(S010) Prospective and Real-Time Data Analysis of Image-Guided Radiotherapy Across a Multinational Pediatrics Consortium: Methodology and Considerations 
(S011) Comparison of Toxicities and Outcomes for Conventional and Hypofractionated Radiation Therapy for Early Glottic Carcinoma
(S013) Adjuvant Radiation Therapy and Temozolomide for Anaplastic Gliomas: The Twelve-Year Washington University Experience
(S014) Gamma Knife Stereotactic Radiosurgery in the Treatment of Brainstem Metastases
(S015) Temporal Lobe Radionecrosis After Skull Base Radiotherapy: Dose-Volume Predictors 
(S012) Prognostic Value of Radiographic Extracapsular Extension in Locally Advanced Non-Oropharyngeal Head and Neck Squamous Cell Cancers
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