Locally advanced pancreatic carcinoma (LAPC) has a poor prognosis and the purpose of treatment is survival prolongation and symptom palliation. Radiotherapy has been reported to reduce pain in LAPC. Stereotactic RT (SBRT) is considered as an emerging radiotherapy technique able to achieve high local control rates with acceptable toxicity. However, its role in pain palliation is not clear. To review the impact on pain relief with SBRT in LAPC patients, a literature search was performed on PubMed, Scopus, and Embase (January 2000–December 2017) for prospective and retrospective articles published in English. Fourteen studies (479 patients) reporting the effect of SBRT on pain relief were finally included in this analysis. SBRT was delivered with both standard and/or robotic linear accelerators. The median prescribed SBRT doses ranged from 16.5 to 45 Gy (median: 27.8 Gy), and the number of fractions ranged from 1 to 6 (median: 3.5). Twelve of the 14 studies reported the percentage of pain relief (in patients with pain at presentation) with a global overall response rate (complete and partial response) of 84.9% (95% CI, 75.8%–91.5%), with high heterogeneity (Q² test: P<0.001; I²=83.63%). All studies reported toxicity data. Acute and late toxicity (grade ≥3) rates were 3.3%–18.0% and 6.0%–8.2%, respectively. Reported gastrointestinal side effects were duodenal obstruction/ulcer, small bowel obstruction, duodenal bleeding, hemorrhage, and gastric perforation. SBRT achieves pain relief in most patients with pancreatic cancer with an acceptable gastrointestinal toxicity rate. Further prospective studies are needed to define optimal dose/fractionation and the best systemic therapies modality integration to reduce toxicity and improve the palliative outcome. Finally, the quality of life and, particularly, pain control should be considered as an endpoint in all future trials on this emerging treatment technique.

Pancreatic cancer represents a modern oncological urgency. Its management is aimed to both distal and local disease control. Resectability is the cornerstone of treatment aim. It influences the clinical presentation’s definitions as up-front resectable, borderline resectable and locally advanced (unresectable). The main treatment categories are neoadjuvant (preoperative), definitive and adjuvant (postoperative). This review will focus on (i) the current indications by the available national and international guidelines; (ii) the current standard indications for target volume delineation in radiotherapy (RT); (iii) the emerging modern technologies (including particle therapy and Magnetic Resonance [MR]-guided-RT); (iv) stereotactic body radiotherapy (SBRT), as the most promising technical delivery application of RT in this framework; (v) a particularly promising dose delivery technique called simultaneous integrated boost (SIB); and (vi) a multimodal integration opportunity: the combination of RT with immunotherapy.

Conventionally fractionated chemoradiation (CRT) or chemotherapy (CHT) are considered as standard options in locally advanced pancreatic cancer (LAPC) while stereotactic body radiotherapy (SBRT) is an emerging treatment in this setting. The aim of this study was to compare two cohorts of LAPC patients treated with SBRT ± CHT vs CRT ± CHT in terms of local control (LC), distant metastases‐free survival (DMFS), progression‐free survival (PFS), overall survival (OS), and toxicity. Eighty patients were included. Patients in the two cohorts were matched according to: age ≤/>65 years, tumor diameter (two cut‐offs: </≥3.0 and </≥3.9 cm), clinical tumor stage and clinical nodal stage, neoadjuvant CHT, and adjuvant CHT. Median prescribed total dose was 30.0 Gy (range: 18.0‐37.5) and 54.0 Gy (18.0‐63.0) in SBRT and CRT cohorts, respectively. Toxicity was evaluated by CTCAE v4.0 scale. Survival curves were calculated by Kaplan‐Meier method. For hypothesis testing an equivalence and a non‐inferiority test was calculated. No statistically significant differences in terms of acute and late toxicity, DMFS, PFS, and OS were recorded among the two cohorts. Median, 1‐, and 2‐year LC was: 16.0 months, 53.1%, and 40.5% in the CRT cohort and 22.0 months, 80.4%, and 49.8% in the SBRT cohort, respectively (P: .017). A statistically non‐inferiority significance was recorded in terms of OS between CRT and SBRT (P = .031). Patients treated with SBRT showed higher LC rate and similar OS compared to CRT. Therefore, the design of confirmatory randomized studies comparing SBRT and CRT seems justified.

Patients (pts) affected with locally advanced rectal cancer (LARC) may respond differently to neoadjuvant chemoradiotherapy (nCRT). The identification of reliable biomarkers able to predict oncological outcomes could help in the development of risk-adapted treatment strategies. It has been suggested that inflammation parameters may have a role in predicting tumor response to nCRT and survival outcomes and in rectal cancer, but no definitive conclusion can be drawn at present. The aim of the current study is to evaluate the role of baseline inflammatory markers as prognostic and predictive factors in a large multicentric Italian cohort of LARC pts. Patients diagnosed with LARC from January 2002 to December 2019 in 9 Italian centers were retrospectively collected. Patients underwent long-course RT with chemotherapy based on fluoropyrimidine ± oxaliplatin followed by surgery. Inflammatory markers were retrieved based on a pre-treatment blood sample including HEI (hemo-eosinophils inflammation index), SII (systemic index of inflammation), NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio) and MLR (monocyte-to-lymphocyte ratio). Outcomes of interest were pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS). 808 pts were analyzed. pCR rate was 22 %, 5yOS and 5yDFS were 84.0% and 63.1% respectively. Multivariate analysis identified that a NLR cut-off value >1.2 and SII cut-off value >500 could predict pCR (p = 0.05 and 0.009 respectively). In addition to age, extramesorectal nodes and RT dose, MLR >0.18 (p = 0.03) and HEI = 3 (p = 0.05) were independent prognostic factors for DFS. Finally, age, RT dose, MLR with a cut-off >0.35 (p = 0.028) and HEI = 3 (p = 0.045) were independent predictors of OS. Higher values of baseline composite inflammatory markers can serve as predictors of lower pCR rates and worse survival outcomes in LARC patients undergoing nCRT. More reliable data from prospective studies could lead to the integration of these inexpensive and easy-to-derive tools into clinical practice.

Systemic inflammation indices were found to be correlated with therapeutic outcome in several cancers. This study retrospectively analyzes the predictive role of a broad range of systemic inflammatory markers in patients with locally advanced cervical cancer (LACC) including patient-, tumor-, and treatment-related potential prognostic factors. All patients underwent definitive chemoradiation and pretreatment values of several inflammatory indices (neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio, monocyte/lymphocyte ratio, systemic immune inflammation index (SII), leukocyte/lymphocyte ratio, combination of platelet count and NLR, aspartate aminotransferase/platelet ratio index, aspartate aminotransferase/lymphocyte ratio index, systemic inflammatory response index, and aspartate transaminase/neutrophil ratio index) were calculated. Their correlation with local control (LC), distant metastasis-free (DMFS), disease-free (DFS), and overall survival (OS) was analyzed. One hundred and seventy-three patients were included. At multivariable analysis significant correlations were recorded among clinical outcomes and older age, advanced FIGO stage, lower hemoglobin levels, larger tumor size, and higher body mass index values. The multivariate analysis showed only the significant correlation between higher SII values and lower DMFS rates (p < 0.01). Our analysis showed no significant correlation between indices and DSF or OS. Further studies are needed to clarify the role of inflammation indices as candidates for inclusion in predictive models in this clinical setting.