Location
Philadelphia, PA
Start Date
3-5-2023 1:00 PM
End Date
3-5-2023 4:00 PM
Description
Purpose/Objective(s): Little is known on optimal management of patients with early onset pancreatic cancer (EOPC), including the role of radiation therapy. As such, we report on a cohort of patients with EOPC (age <55 years) who was treated with neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT).
Materials/Methods: This was a single institution retrospective review of patients with EOPC who were treated with upfront chemotherapy followed by SBRT with or without surgical resection. Endpoints included overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and treatment-related toxicity. Next-generation sequencing (NGS) was performed on select patient tumor specimens.
Results: From 2016-2021, 47 patients met the inclusion criteria. Median age was 50.4 years (range, 36.4 – 54.7 years). Median induction chemotherapy duration was 4 months (range, 2.5 – 9 months). The majority (46/47, 97.9%) of patients received 33 Gy in 5 fractions. Following SBRT, 43 patients (91%) underwent surgical exploration, with extent of vascular involvement on post-SBRT imaging precluding exploration in 4 patients (9%). Gross resection was achieved in 33 patients (70.2%), with intraoperative metastatic disease precluding resection in 8 patients (17%) and intraoperative extent of vascular involvement of the primary tumor precluding resection in 4 patients (9%). Median OS, LPFS, DMFS, and PFS were 14.2 months, 11.6 months, 8.9 months, and 8.1 months respectively. Six-month and 1-year LPFS were 88.3% and 45.4%, respectively. Chemotherapy duration (> 4 months) was associated with improved median OS (16.5 vs 10.1 months, p=0.005), LPFS (10.1 vs 4.9 months, p=0.002), DMFS (9.7 vs 5.2 months, p=0.014), and PFS (9.7 vs 5.2 months, p=0.020). Normalization of CA 19-9 (< 34 vs > 34 U/ml) after chemotherapy was associated with improved median DMFS (not reached vs 5.6 months, p=0.003) and PFS (11.3 vs 5.6 months, p=0.022). Grade 3+ rates of chemotherapy and radiation-related toxicity were 14.9% and 2.1% respectively. Clavien-Dindo 3b toxicity rate was 3.0%. A total of 15 patients underwent NGS, with mutations being found in KRAS (10/15, 66.7%), TP53 (7/15, 46.7%), NOTCH 1/2 (3/15, 20%), CDK2NA (2/15, 13.3%), and SMAD4(1/15, 6.7%).
Conclusion: Multi-modality therapy for EOPC was administered with low toxicity, but outcomes remain suboptimal. Induction chemotherapy duration > 4 months and normalization of CA 19-9 after chemotherapy were associated with improved outcomes, suggesting a role for extended durations of systemic therapy titrated to CA 19-9 response before transitioning to local therapy. The high rate of local failure and the low rate of grade 3+ toxicity also suggest a role for intensifying local therapy in this population, such as radiation dose escalation, expansion of the radiation target volume, and more aggressive surgical techniques.
Embargo Period
7-5-2023
Included in
Neoadjuvant Chemotherapy and Stereotactic Body Radiation Therapy in Patients with Early Onset Pancreatic Cancer: Clinical Outcomes and Toxicity
Philadelphia, PA
Purpose/Objective(s): Little is known on optimal management of patients with early onset pancreatic cancer (EOPC), including the role of radiation therapy. As such, we report on a cohort of patients with EOPC (age <55 >years) who was treated with neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT).
Materials/Methods: This was a single institution retrospective review of patients with EOPC who were treated with upfront chemotherapy followed by SBRT with or without surgical resection. Endpoints included overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and treatment-related toxicity. Next-generation sequencing (NGS) was performed on select patient tumor specimens.
Results: From 2016-2021, 47 patients met the inclusion criteria. Median age was 50.4 years (range, 36.4 – 54.7 years). Median induction chemotherapy duration was 4 months (range, 2.5 – 9 months). The majority (46/47, 97.9%) of patients received 33 Gy in 5 fractions. Following SBRT, 43 patients (91%) underwent surgical exploration, with extent of vascular involvement on post-SBRT imaging precluding exploration in 4 patients (9%). Gross resection was achieved in 33 patients (70.2%), with intraoperative metastatic disease precluding resection in 8 patients (17%) and intraoperative extent of vascular involvement of the primary tumor precluding resection in 4 patients (9%). Median OS, LPFS, DMFS, and PFS were 14.2 months, 11.6 months, 8.9 months, and 8.1 months respectively. Six-month and 1-year LPFS were 88.3% and 45.4%, respectively. Chemotherapy duration (> 4 months) was associated with improved median OS (16.5 vs 10.1 months, p=0.005), LPFS (10.1 vs 4.9 months, p=0.002), DMFS (9.7 vs 5.2 months, p=0.014), and PFS (9.7 vs 5.2 months, p=0.020). Normalization of CA 19-9 (< 34 vs > 34 U/ml) after chemotherapy was associated with improved median DMFS (not reached vs 5.6 months, p=0.003) and PFS (11.3 vs 5.6 months, p=0.022). Grade 3+ rates of chemotherapy and radiation-related toxicity were 14.9% and 2.1% respectively. Clavien-Dindo 3b toxicity rate was 3.0%. A total of 15 patients underwent NGS, with mutations being found in KRAS (10/15, 66.7%), TP53 (7/15, 46.7%), NOTCH 1/2 (3/15, 20%), CDK2NA (2/15, 13.3%), and SMAD4(1/15, 6.7%).
Conclusion: Multi-modality therapy for EOPC was administered with low toxicity, but outcomes remain suboptimal. Induction chemotherapy duration > 4 months and normalization of CA 19-9 after chemotherapy were associated with improved outcomes, suggesting a role for extended durations of systemic therapy titrated to CA 19-9 response before transitioning to local therapy. The high rate of local failure and the low rate of grade 3+ toxicity also suggest a role for intensifying local therapy in this population, such as radiation dose escalation, expansion of the radiation target volume, and more aggressive surgical techniques.
Comments
Awarded PCOM Philadelphia Research Day 2023 CCDA Award for Research Excellence.