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Retinol

patients received 10 mg of hyperbaric bupivacaine 0.5% in 2 mL volume and 5 μg of dexmedetomidine in 1 mL volume intrathecally.

patients received 10 mg of hyperbaric bupivacaine 0.5% in 2 mL volume and 0.5 mg morphine sulphate in 1 mL volume intrathecally.

patients received 10 mg of hyperbaric bupivacaine 0.5% in 2 mL volume and 5 μg of dexmedetomidine plus 0.5 mg of morphine sulphate in 1 mL volume intrathecally.

Intrathecal injection as the patients will be placed in the sitting position and a 25-gauge Quincke needle will be placed in the L2-3 or L3-4 interspaces with injection of morphine sulphate .

Morphine Sulfate

Intrathecal injection as the patients will be placed in the sitting position and a 25-gauge Quincke needle will be placed in the L2-3 or L3-4 interspaces.

this work aims to investigate the effect of intrathecal administration of Morphine, Dexmedetomidine or both in combination on cellular immunity and cytokine production in patients undergoing major abdominal cancer surgeries.

Intrathecal (IT) adjuvants prolong the duration of spinal anesthesia and postoperative analgesia thereby reducing the requirement of postoperative supplemental analgesics. The incorporation of adjuvants also lowers the overall dose of local anesthetic and hence associated side effects. Morphine has been used widely to alleviate various types of pain and to supplement general anesthesia. On the other hand, morphine has been reported to possess some immunosuppressive effects. Postoperative immunity is also important in conjunction with defence against malignant tumour. Dexmedetomidine is a highly selective α2 agonist with analgesia, sedation, anxiolysis, and sympatholysis as its useful pharmacological actions. The extended analgesic efficacy of IT dexmedetomidine (ITD) in the postoperative period has been shown in a few clinical studies. In addition, current insights have identified that dexmedetomidine has a capacity in inhibiting the overproduction of a variety of inflammatory molecules including TNF-α, IL-1β, and IL-6 in several acute inflammatory animal models.

Effect of Intrathecal Morphine, Dexmedetomidine or Both in Combination to Bupivacaine on Immunity

Effect of Intrathecal Morphine, Dexmedetomidine or Both in Combination to Bupivacaine on Immunity in Patients Undergoing Major Abdominal Cancer Surgeries

interleukin-1B, interleukin-6, interleukin-10 and tumor necrosis factor

Assiut University

Lecturer of anesthesia, ICU and pain managment

Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

HYpofractionated, Dose-redistributed RAdiotherapy (HYDRA)

conventional fractionated radiotherapy

Joris BW Elbers, MD, PhD

Jos Elbers

Radiotherapy for advanced-stage head and neck squamous cell carcinoma (HNSCC) results in an unfavorable 5-year overall survival of 40%, and there is a strong biological rationale for improving outcome by combinatorial treatment with immunotherapy. However, also immunosuppressive effects of radiotherapy have been reported and recently a randomized phase-III trial failed to show any survival benefit following the combination of a PD-L1 inhibitor with chemoradiotherapy. The hypothesis is that the combination of these individually effective treatments failed because of radiation-induced lymphodepletion and that the key therefore lies in reforming conventional radiotherapy, which typically consists of large lymphotoxic radiation fields of 35 fractions. By integrating modern radiobiology and individually established innovative radiotherapy concepts, the patient's immune system could be maximally retained. This will be achieved by 1) increasing the radiation dose per fraction so that the total number of fractions can be reduced (HYpofractionation), 2) by redistributing the radiation dose towards a higher peak dose within the tumor center and a lowered elective-field dose (Dose-redistribution) and 3) by using RAdiotherapy with protons instead of photons (HYDRA).

The objectives of this study are to determine the safety of HYDRA with protons and photons by conducting two parallel phase-I trials. HYDRA's efficacy will be compared to standard of care (SOC). The immune effects of HYDRA-protons will be evaluated by longitudinal immune profiling and compared to HYDRA-photons and SOC (with protons and photons). There will be a specific focus on actionable immune targets and their temporal patterns that can be tested in future hypofractionated-immunotherapy combination trials. This trial therefore is an important step towards future personalized immuno-radiotherapy combinations with the ultimate goal to improve survival for patients with HNSCC.

The HYDRA dose prescriptions are, in 20 fractions (instead of the conventional 35 fractions):

* Inhomogeneous focal boost on the macroscopic gross tumor volume (GTVprimary tumor and GTVnodes) on FDG-PET: mean dose 59Gy, max dose 63Gy.
* The mean dose of 59Gy corresponds to an equal late normal tissue toxicity probability after conventionally fractionated radiotherapy of 70Gy in 35 fractions, considering an α/β=3 for normal tissue.
* Simultaneous integrated boost (SIB) on the clinical target volume (CTV-P1 = GTV+5mm): 55Gy
* Elective field / CTV-P2 (GTV+10mm): 40Gy

Patients who receive the HYDRA intervention treatment, as well as patients who receive standard of care may require the addition of a concurrent radiosensitizer based on clinicopathological features according to standard of care. Currently, the only two registered radiosensitizers are platinum-based chemotherapy (cisplatin/carboplatin) and cetuximab. These radiosensitizers should be administered according to standard care treatment protocols.

Two parallel, non-comparative phase-I trials of HYDRA-protons run at HollandPTC (group 1, n=25) and HYDRA-photons (group 3, n=25) run at the Erasmus MC. Toxicity will be monitored until 1 year after the last patient has completed HYDRA. This will result in a median follow-up of approximately 2 years. Patients will subsequently receive follow-up according to standard of care up to 5 years after treatment for the evaluation of very late-onset toxicity.

For translational immune profiling, HYDRA-protons and HYDRA-photons will be randomized by minimization (1:1 ratio) against SOC: conventional fractionated proton therapy in HPTC (group 2, n=25) and conventional fractionated photon therapy in the Erasmus MC (group 4, n=25), respectively.

HYpofractionated, Dose-redistributed RAdiotherapy With Protons and Photons in HNSCC

HYpofractionated, Dose-redistributed RAdiotherapy With Protons and Photons to Combat Radiation-induced Immunosuppression in Head and Neck Squamous Cell Carcinoma (HYDRA)

HYDRA is randomized with standard of care for translational research purposes; a direct comparison of toxicity will statistically not be conclusive and is outside the scope of this study.

Objective response rate 3 months after HYDRA (group 1 and 3), defined by radiological response on CT-scans or MRI using RECIST version 1.1 and/or histopathological confirmation of residual disease, in comparison to standard of care (group 2 and 4, respectively), 3 months after end of treatment

Efficacy of HYDRA (group 1 and 3) in terms of in-field and nodal elective field tumor control, 1 year after the last patient is included, in comparison to group 2 and 4, respectively.

Numbers and phenotype of peripheral immune cell populations in blood at baseline, related to patient- and tumor characteristics, and differences between temporal changes of these immune markers during/after treatment at 6 timepoints in group 1-4.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Effect of Intrathecal Morphine, Dexmedetomidine or Both in Combination to Bupivacaine on Immunity	NCT03024957	Immune System S...	Morphine Sulfat... Dexmedetomidine Bupivacaine	20 Years - 70 Years	Assiut University
HYpofractionated, Dose-redistributed RAdiotherapy With Protons and Photons in HNSCC	NCT05364411	Head and Neck S... Hypofractionati... Radiotherapy Proton Therapy Immune System S...	HYpofractionate... conventional fr...	18 Years -	Erasmus Medical Center
HYpofractionated, Dose-redistributed RAdiotherapy With Protons and Photons in HNSCC	NCT05364411	Head and Neck S... Hypofractionati... Radiotherapy Proton Therapy Immune System S...	HYpofractionate... conventional fr...	18 Years -	Erasmus Medical Center
Effect of Intrathecal Morphine, Dexmedetomidine or Both in Combination to Bupivacaine on Immunity	NCT03024957	Immune System S...	Morphine Sulfat... Dexmedetomidine Bupivacaine	20 Years - 70 Years	Assiut University

Spots Global Cancer Trial Database for immune system suppression