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).

Impact of Pre-Treatment NLR and Other Hematologic Biomarkers on the Outcomes of Early-Stage Non-Small-Cell Lung Cancer Treated with Stereotactic Body Radiation Therapy

Introduction: We evaluated the association of pre-treatment immunologic biomarkers on the outcomes of early-stage non-small-cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT). Materials and methods: In this retrospective study, all newly diagnosed early-stage NSCLC treated with SBRT between January 2010 and December 2017 were screened and included for further analysis. The pre-treatment neutrophil-lymphocyte ratio (NLR), monocyte lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) were calculated. Overall survival (OS) and recurrence-free survival (RFS) were estimated by Kaplan–Meier. Multivariable models were constructed to determine the impact of different biomarkers and the Akaike information criterion (AIC), index of adequacy, and scaled Brier scores were calculated. Results: A total of 72 patients were identified and 61 were included in final analysis. The median neutrophil count at baseline was 5.4 × 109/L (IQR: 4.17–7.05 × 109/L). Median lymphocyte count was 1.63 × 109/L (IQR: 1.29–2.10 × 109/L), median monocyte count was 0.65 × 109/L (IQR: 0.54–0.83 × 109/L), median platelet count was 260.0 × 109/L (IQR: 211.0–302.0 × 109/L). The median NLR was 3.42 (IQR: 2.38–5.04), median MLR was 0.39 (IQR: 0.31–0.53), and median PLR was 156.4 (IQR: 117.2–197.5). On multivariable regression a higher NLR was associated with worse OS (p = 0.01; HR-1.26; 95% CI 1.04–1.53). The delta AIC between the two multivariable models was 3.4, suggesting a moderate impact of NLR on OS. On multivariable analysis, higher NLR was associated with poor RFS (p = 0.001; NLR^1 HR 0.36; 0.17–0.78; NLR^2 HR-1.16; 95% CI 1.06–1.26) with a nonlinear relationship. The delta AIC between the two multivariable models was 16.2, suggesting a strong impact of NLR on RFS. In our cohort, MLR and PLR were not associated with RFS or OS in multivariable models. Conclusions: Our study suggests NLR, as a biomarker of systemic inflammation, is an independent prognostic factor for OS and RFS. The nonlinear relationship with RFS may indicate a suitable immunological environment is needed for optimal SBRT action and tumoricidal mechanisms. These findings require further validation in independent cohorts.