A non-surgical COMBO-therapy approach for locally advanced unresectable pancreatic adenocarcinoma: preliminary results of a prospective study

Parisi, Silvana; Ferini, Gianluca; Cacciola, Alberto; Lillo, Sara; Tamburella, C.; Santacaterina, Anna; Bottari, Antonio; Brogna, A.; Ferrantelli, Giacomo; Pontoriero, Antonio; Minutoli, Fabio; Pergolizzi, Stefano

doi:10.1007/s11547-021-01441-w

Cited by 22 publications

(21 citation statements)

References 30 publications

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“…As the dose regimens explored in this study existed within the range of doses used in real-world clinical settings, our results are expected to be relatively feasible for translation to patients. Indeed, these findings further substantiate the rationale for delivering a stereotactic hypofractionated boost to any residual radioresistant cancer tissue after a normofractionated radiotherapy course (20), as encouraged by some preliminary clinical results (21), including also inoperable stage III lung cancer patients who were incompletely responsive to standard radiochemotherapy (22). However, further investigations are necessary to establish an appropriate dose-fractionation strategy.…”

Section: Discussionsupporting

confidence: 58%

Dynamic alterations in PD-1/PD-L1 expression level and immune cell profiles based on radiation response status in mouse tumor model

et al. 2022

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IntroductionBased on the immunologic effects of anti-cancer treatment and their therapeutic implications, we evaluated radiotherapy (RT)-induced dynamic alterations in programmed death-1 (PD-1)/PD ligand-1 (PD-L1) expression profiles.MethodsLocal RT with 2 Gy × 5 or 7.5 Gy × 1 was administered to the CT26 mouse model. Thereafter, tumors were resected and evaluated at the following predefined timepoints according to radiation response status: baseline, early (immediately after RT), middle (beginning of tumor shrinkage), late (stable status with RT effect), and progression (tumor regrowth). PD-1/PD-L1 activity and related immune cell profiles were quantitatively assessed.ResultsRT upregulated PD-L1 expression in tumor cells from the middle to late phase; however, the levels subsequently decreased to levels comparable to baseline in the progression phase. RT with 2 Gy × 5 induced a higher frequency of PD-L1+ myeloid-derived suppressor cells, with a lesser degree of tumor regression, compared to 7.5 Gy. The proportion of PD-1+ and interferon (IFN)-γ+CD8α T cells continued to increase. The frequency of splenic PD-1+CD8+ T cells was markedly elevated, and was sustained longer with 2 Gy × 5. Based on the transcriptomic data, RT stimulated the transcription of immune-related genes, leading to sequentially altered patterns.DiscussionThe dynamic alterations in PD-1/PD-L1 expression level were observed according to the time phases of tumor regression. This study suggests the influence of tumor cell killing and radiation dosing strategy on the tumor immune microenvironment.

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Section: Discussionsupporting

confidence: 58%

Dynamic alterations in PD-1/PD-L1 expression level and immune cell profiles based on radiation response status in mouse tumor model

et al. 2022

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“…Additionally, no DVC indication is made for RT schedules combining different radiation dose sizes, as in the cases of a stereotactic boost to a limited tumor site after a more extended normofractionated irradiation [ 96 , 97 ] or of a large spatially fractionated dose administration before a homogeneously delivered hypofractionated palliative course [ 98 ].…”

Section: Discussionmentioning

confidence: 99%

Dose–Volume Constraints fOr oRganS At risk In Radiotherapy (CORSAIR): An “All-in-One” Multicenter–Multidisciplinary Practical Summary

et al. 2022

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Background: The safe use of radiotherapy (RT) requires compliance with dose/volume constraints (DVCs) for organs at risk (OaRs). However, the available recommendations are sometimes conflicting and scattered across a number of different documents. Therefore, the aim of this work is to provide, in a single document, practical indications on DVCs for OaRs in external beam RT available in the literature. Material and Methods: A multidisciplinary team collected bibliographic information on the anatomical definition of OaRs, on the imaging methods needed for their definition, and on DVCs in general and in specific settings (curative RT of Hodgkin’s lymphomas, postoperative RT of breast tumors, curative RT of pediatric cancers, stereotactic ablative RT of ventricular arrythmia). The information provided in terms of DVCs was graded based on levels of evidence. Results: Over 650 papers/documents/websites were examined. The search results, together with the levels of evidence, are presented in tabular form. Conclusions: A working tool, based on collected guidelines on DVCs in different settings, is provided to help in daily clinical practice of RT departments. This could be a first step for further optimizations.

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“…Newer SRT protocols and patient-tailored dose planning seem to correlate with improved functional outcomes and LC, 16,29,33 similarly to other lesions benefitting from a stereotactic approach. [37][38][39] In this review, we found that spine metastatic HCCs show favorable postradiotherapy clinical and radiological responses, with acceptable complication rates.…”

Section: Discussionmentioning

confidence: 91%

The role of radiation therapy in the treatment of spine metastases from hepatocellular carcinoma: a systematic review and meta-analysis

Ferini¹,

Palmisciano

Scalia

et al. 2022

Neurosurgical Focus

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OBJECTIVE Spine hepatocellular carcinoma (HCC) metastases severely worsen quality of life and prognosis, with the role of radiotherapy being controversial. The authors systematically reviewed the literature on radiotherapy for spine metastatic HCCs. METHODS The PubMed, Scopus, Web of Science, and Cochrane databases were searched according to the PRISMA guidelines to include studies of radiotherapy for spine metastatic HCCs. Outcomes, complications, and local control were analyzed with indirect random-effect meta-analyses. RESULTS The authors included 12 studies comprising 713 patients. The median time interval from diagnosis of HCC to spine metastases was 12 months (range 0–105 months). Most lesions were thoracic (35.9%) or lumbar (24.7%). Radiotherapy was delivered with conventional external-beam (67.3%) or stereotactic (31.7%) techniques. The median dose was 30.3 Gy (range 12.5–52 Gy) in a median of 5 fractions (range 1–20 fractions). The median biologically effective dose was 44.8 Gy10 (range 14.4–112.5 Gy10). Actuarial rates of postradiotherapy pain relief and radiological response were 87% (95% CI 84%–90%) and 70% (95% CI 65%–75%), respectively. Radiation-related adverse events and vertebral fractures had actuarial rates of 8% (95% CI 5%–11%) and 16% (95% CI 10%–23%), respectively, with fracture rates significantly higher after stereotactic radiotherapy (p = 0.033). Fifty-eight patients (27.6%) had local recurrences after a median of 6.8 months (range 0.1–59 months), with pooled local control rates of 61.6% at 6 months and 40.8% at 12 months, and there were no significant differences based on radiotherapy type (p = 0.068). The median survival was 6 months (range 0.1–62 months), with pooled rates of 52.5% at 6 months and 23.4% at 12 months. CONCLUSIONS Radiotherapy in spine metastatic HCCs shows favorable rates of pain relief, radiological responses, and local control. Rates of postradiotherapy vertebral fractures are higher after high-dose stereotactic radiotherapy.

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A non-surgical COMBO-therapy approach for locally advanced unresectable pancreatic adenocarcinoma: preliminary results of a prospective study

Cited by 22 publications

References 30 publications

Dynamic alterations in PD-1/PD-L1 expression level and immune cell profiles based on radiation response status in mouse tumor model

Dynamic alterations in PD-1/PD-L1 expression level and immune cell profiles based on radiation response status in mouse tumor model

Dose–Volume Constraints fOr oRganS At risk In Radiotherapy (CORSAIR): An “All-in-One” Multicenter–Multidisciplinary Practical Summary

The role of radiation therapy in the treatment of spine metastases from hepatocellular carcinoma: a systematic review and meta-analysis

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