Upfront Chemotherapy Followed by Stereotactic Body Radiation Therapy with or without Surgery in Older Patients with Localized Pancreatic Cancer: A Single Institution Experience and Review of the Literature

Objective: To report on clinical outcomes and toxicity in older (age ≥ 70 years) patients with localized pancreatic cancer treated with upfront chemotherapy followed by stereotactic body radiation therapy (SBRT) with or without surgery. Methods: Endpoints included overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and toxicity. Results: A total of 57 older patients were included in the study. Median OS was 19.6 months, with six-month, one-year, and two-year OS rates of 83.4, 66.5, and 42.4%. On MVA, resection status (HR: 0.30, 95% CI 0.12–0.91, p = 0.031) was associated with OS. Patients with surgically resected tumors had improved median OS (29.1 vs. 7.0 months, p < 0.001). On MVA, resection status (HR: 0.40, 95% CI 0.17–0.93, p = 0.034) was also associated with PFS. Patients with surgically resected tumors had improved median PFS (12.9 vs. 1.6 months, p < 0.001). There were 3/57 cases (5.3%) of late grade 3 radiation toxicity and 2/38 cases (5.3%) of Clavien-Dindo grade 3b toxicity in those who underwent resection. Conclusion: Multimodality therapy involving SBRT is safe and feasible in older patients with localized pancreatic cancer. Surgical resection was associated with improved clinical outcomes. As such, older patients who complete chemotherapy should not be excluded from aggressive local therapy when possible.

Lung stereotactic body radiation therapy: personalized PTV margins according to tumor location and number of four-dimensional CT scans

Objectives To characterise the motion of pulmonary tumours during stereotactic body radiation therapy (SBRT) and to evaluate different margins when creating the planning target volume (PTV) on a single 4D CT scan (4DCT). Methods We conducted a retrospective single-site analysis on 30 patients undergoing lung SBRT. Two 4DCTs (4DCT1 and 4DCT2) were performed on all patients. First, motion was recorded for each 4DCT in anterior–posterior (AP), superior-inferior (SI) and rightleft (RL) directions. Then, we used 3 different margins (3,4 and 5 mm) to create the PTV, from the internal target volume (ITV) of 4DCT1 only (PTV D1 + 3, PTV D1 + 4, PTV D1 + 5). We compared, using the Dice coefficient, the volumes of these 3 PTVs, to the PTV actually used for the treatment (PTVttt). Finally, new treatment plans were calculated using only these 3 PTVs. We studied the ratio of the D2%, D50% and D98% between each new plan and the plan actually used for the treatment (D2% PTVttt, D50% PTVttt, D50% ITVttt D98% PTVttt). Results 30 lesions were studied. The greatest motion was observed in the SI axis (8.8 ± 6.6 [0.4–25.8] mm). The Dice index was higher when comparing PTVttt to PTV D1 + 4 mm (0.89 ± 0.04 [0.82–0.98]). Large differences were observed when comparing plans relative to PTVttt and PTV D1 + 3 for D98% PTVttt (0.85 ± 0.24 [0.19–1.00]). and also for D98% ITVttt (0.93 ± 0.12 [0.4–1.0]).D98% PTVttt (0.85 ± 0.24 [0.19–1.00], p value = 0.003) was statistically different when comparing plans relative to PTVttt and PTV D1 + 3. No stastistically differences were observed when comparing plans relative to PTVttt and PTV D1 + 4. A difference greater than 10% relative to D98% PTVttt was found for only in one UL lesion, located under the carina. Conclusion A single 4DCT appears feasible for upper lobe lesions located above the carina, using a 4-mm margin to generate the PTV. Advance in knowledge Propostion of a personalized SBRT treatment (number of 4DCT, margins) according to tumor location (above or under the carina).

Changes of immune status in patients with different PD-L1 expression after stereotactic body radiation therapy of oligometastasis

Purpose. To study the influence of PD-L1 expression on the dynamics of immunological changes before and at different intervals after stereotactic body radiation therapy (SBRT) of metastatic lesions in patients with metastatic forms of solid tumors. Materials and methods. A quantitative assessment and analysis of blood immunological parameters was conducted before irradiation, via 3-4 weeks and via 6-8 weeks after SBRT in patients with malignant tumors with oligometastases in the liver or lungs, in groups with negative and positive expression of PD-L1. All peripheral blood samples were analyzed by flow cytometry. Statistical analysis was performed using Friedman and Nemenyi criteria. Results. 3-4 weeks after the end of SBRT in group CPS <1 we observed statistically significant increase of activated T-helpers (CD3+CD4+HLA-DR+), activated cytotoxic T-lymphocytes (CD3+СD8+HLA-DR+), T-lymphocytes (CD3+CD19-) and T-helpers (CD3+CD4+). Wherein, activated T-helpers and activated cytotoxic T-lymphocytes statistically significantly increased 6-8 weeks after SBRT compared with the study before irradiation. In group CPS> 1, we revealed statistically significant increase of activated T-helpers 6-8 weeks after and decrease of T-regulatory lymphocytes (CD4+CD25brightCD127low) 3-4 weeks after completion of SBRT compared with the study before radiotherapy. When we analyzed the indicators by the TPS index, most of the statistically significant changes were recorded in the group with negative expression (TPS <1): increasing of activated T-helpers and activated cytotoxic T-lymphocytes 3-4 weeks and 6-8 weeks after SBRT and decreasing of T-regulatory lymphocytes 3-4 weeks after irradiation compared with the study before irradiation. Conclusion. Groups with negative PD-L1 expression (CPS <1 and TPS <1) are associated with a more activated antitumor T-cell immune response compared to patients with positive PD-L1 status (CPS≥1 and TPS≥1), however, further researches are needed.