SBRT versus chemoradiation after induction chemotherapy in locally advanced pancreatic cancer

The study described compares the outcomes of **Stereotactic Body Radiation Therapy (SBRT)** versus **Conventional Chemoradiation (CRT)** following induction chemotherapy in patients with **Locally Advanced Pancreatic Cancer (LAPC)** and **Borderline Resectable Pancreatic Cancer (BRPC)**. Below is a detailed explanation of the findings and the concepts involved:

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### **Key Findings from the Study**

1. **Resectability**:

• Resectability was achieved in **15% of patients**, and all of these were from the SBRT arm. Importantly, all patients who became resectable were initially diagnosed with LAPC.
• CRT did not lead to any cases of resectability.

2. **Survival Outcomes**:

• Patients treated with SBRT had a **mean overall survival (OS)** of **21.8 months** compared to **13 months** for CRT.
• SBRT also resulted in a longer **local progression-free survival (LPFS)** (14 months vs. 8.6 months with CRT).
• The **one-year overall survival rate** was significantly higher with SBRT (**80%**) compared to CRT (**45%**).

3. **Toxicity and Quality of Life**:

• SBRT showed **no grade 3 or 4 toxicities**, whereas CRT was associated with higher toxicity levels.
• Patients in the SBRT group reported better **quality of life (QoL)** scores compared to those receiving CRT.

4. **Immune and Inflammatory Markers**:

• Lower **neutrophil-to-lymphocyte ratio (NLR)** and **platelet-to-lymphocyte ratio (PLR)** were associated with improved survival outcomes, suggesting these markers may be predictive of better treatment responses.

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### **Definitions and Concepts**

#### **Locally Advanced Pancreatic Cancer (LAPC)**:

• LAPC refers to pancreatic cancer that has spread to nearby structures (e.g., blood vessels), making surgical removal (resection) impossible or highly challenging. It has not metastasized to distant organs but is confined to the pancreas and surrounding areas.

#### **Borderline Resectable Pancreatic Cancer (BRPC)**:

• BRPC is a stage of pancreatic cancer where the tumor is in close proximity to major blood vessels, making surgical resection technically possible but with a high risk of incomplete removal. Neoadjuvant (pre-surgical) treatments like chemotherapy or radiation are often used to shrink the tumor and improve the chances of a successful surgery.

#### **Induction Chemotherapy**:

• Induction chemotherapy refers to the initial phase of systemic treatment aimed at reducing tumor size, controlling disease progression, and improving the likelihood of subsequent treatments (e.g., radiation or surgery). In this study, patients received either:
• **Modified FOLFIRINOX**: A combination of chemotherapy drugs (5-FU, leucovorin, irinotecan, and oxaliplatin) commonly used for aggressive pancreatic cancer.
• **Gemcitabine with nab-paclitaxel**: Another chemotherapy regimen used for pancreatic cancer.

#### **Stereotactic Body Radiation Therapy (SBRT)**:

• SBRT is a highly precise form of radiation therapy that delivers high doses of radiation to the tumor in a few sessions (typically 5–6 fractions in this study). It minimizes damage to surrounding healthy tissues and is associated with fewer side effects than conventional radiation.

#### **Conventional Chemoradiation (CRT)**:

• CRT combines standard radiation therapy with chemotherapy (in this study, Capecitabine was used as the radiosensitizing agent). It is typically delivered over a longer duration (e.g., 25 fractions in this study) and is associated with higher toxicity compared to SBRT.

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### **Comparison of SBRT vs. CRT in LAPC**

#### **Advantages of SBRT**:

• **Higher Resectability Rates**: SBRT enabled some patients with LAPC to achieve resectability, whereas CRT did not.
• **Improved Survival**: SBRT significantly extended overall survival (21.8 months vs. 13 months with CRT) and local progression-free survival (14 months vs. 8.6 months with CRT).
• **Better Quality of Life**: Patients receiving SBRT reported improved QoL scores.
• **Lower Toxicity**: SBRT was associated with no grade 3 or 4 toxicities, making it a safer option compared to CRT.

#### **Limitations of CRT**:

• CRT showed lower efficacy in terms of resectability and survival outcomes.
• Higher toxicity levels were observed, which could negatively impact patient quality of life.

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### **Conclusion**

The study suggests that **SBRT following induction chemotherapy** is superior to **CRT** for patients with LAPC and BRPC in terms of:

• **Resectability**: SBRT increases the likelihood of converting unresectable tumors to resectable ones.
• **Survival**: SBRT provides better overall survival and local progression-free survival.
• **Quality of Life and Safety**: SBRT is associated with fewer toxicities and improved patient-reported outcomes.

However, these findings are preliminary due to the small sample size (20 patients) and single-institution nature of the trial. Larger, multicenter randomized trials are needed to confirm these results and establish SBRT as a standard of care for LAPC and BRPC.