Effectiveness and tolerability of radiotherapy for patients with indolent non-Hodgkin’s lymphoma: a monocenter analysis

To analyze the effectiveness and toxicities of radiotherapy in indolent non-Hodgkin’s lymphoma (iNHL) patients treated in our institution. Patients with iNHL treated with radiotherapy between 1999 and 2016 were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were local control (LC), overall survival (OS) and toxicities. PFS, LC, and OS were analyzed using Kaplan–Meier method. Log-rank test was used to investigate the differences between subgroups. Cox proportional hazard model was used for univariate continuous analysis. Seventy-five patients were identified in our institutional database between 1999 and 2016. Fifty-eight (77.3%) had stage I after Ann-Arbor and 17 patients (22.7%) had stage II. The median follow-up was 87 months (95% CI 72–102 months). Median single dose per fraction was 2.0 Gy (range 1.5–2 Gy) and median total dose was 30.6 Gy (range 16–45 Gy). Radiotherapy was performed in 2D (n = 10; 13.3%), 3D (n = 63; 84.0%) and VMAT (n = 2; 2.7%) techniques, respectively. The median PFS was 14.0 years (95% CI 8.3–19.7 years). The estimated PFS after 5 and 10 years were 73.0% and 65.5% in Kaplan–Meier analysis, respectively. The 5- and 10-year LC were 94.9% and 92.3%, respectively. The 5- and 10-year OS were 88.6% and 73.9%. In univariate analyses of PFS, younger patients (≤ 60 years old) had significantly superior PFS to those older than 60 years old (5-year PFS 81.9% vs. 65.1%, p = 0.021). Dose escalation > 36.0 Gy had no prognostic influence in term of PFS (p = 0.425). Extranodal involvement, stage and histology had no prognostic impact on PFS. Depending on the site of lymphomas, the most common acute side effects were: dermatitis CTCAE° I–II (8.0%), xerostomia CTC° I (8.0%), cataract CTC° I (12.0%) and dry eyes CTC° I–II (14.6%). No adverse event CTC° III was reported. Most acute side effects recovered at 3 to 6 months after radiotherapy except for CTC° I cataract and xerostomia. Local Radiotherapy was highly effective for treatment of early stage iNHL with no serious side effects in our cohort. The most acute CTCAE° I–II side effects recovered 3 to 6 months later. Technique advances seem to have further improved effectiveness and tolerability of radiotherapy.Trial registration: Local ethics committee of Ludwig-Maximilian-University (LMU) Munich approved this retrospective analysis on the May 7th, 2019 (Nr. 19–137).

585. Safety of Pfizer-BioNtech COVID-19 Vaccine in Healthcare Workers, Singapore

Background On 14 December 2020, the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine was granted emergency use authorization in Singapore. Healthcare workers (HCW) were prioritized to receive the vaccine. We aim to investigate the side effects and risk factors for allergic reactions in our institution. Methods All HCW vaccinations were recorded in an electronic centralized database. All reactions occurring within a 30-minute observation period post vaccination were recorded. Staff were required to report any vaccine-related medical consult including hospitalization occurring within 14 days after vaccination. Moderate/severe reactions were assessed by a medical team and determined if the reactions were probable allergic reactions with consultation with an Allergist. We extracted data from 8 Jan 2021 to 30 April 2021. Results 5030 and 159 HCW completed 2 doses and 1 dose of the vaccine respectively. There were 1056 HCWs (20.3%) with self-reported pre-existing allergy. There were 114 (1.1%) reactions occurring without the 30-minute observation period, and 64 (56.1%) were related to first dose of vaccine. The most common side effect experienced was aches or pain on any part of the body (n=46, 40.4%) followed by fatigue and/or giddiness (n=45, 39.5%), palpitations and/or shortness of breath (n=22, 19.3%), systemic rash and/or angioedema (n=12, 10.5%) and nausea and/or vomiting (n=12, 10.5%). A total of 23 HCWs complained of systemic rash and/or angioedema that occurred anytime post vaccination. Fifteen HCWs (0.29% of the cohort) were considered to have probable allergic reaction to the vaccine. None of the reactions were classified as anaphylaxis or severe reactions, but 4 HCWs required short hospitalization stay for observation. HCWs with pre-existing allergy had 2.6 times the risk of having probable vaccine-related allergic reaction than HCWs without pre-existing allergy (RR 2.6, 95% CI 0.9 to 7.3, p=0.068) but this was not statistically significant. Conclusion No anaphylaxis or severe reactions were observed in our institution. Acute side effects in our cohort were in line with published trial reports. We noted a raised relative risk of 2.6 of pre-existing allergy with probable vaccine-related allergic reaction but this was not statistically significant. Disclosures All Authors: No reported disclosures

Acute side effects after definitive stereotactic body radiation therapy (SBRT) for patients with clinically localized or locally advanced prostate cancer: a single institution prospective study

Background The aim of the study was to evaluate acute side effects after extremely hypofractionated intensity-modulated radiotherapy (IMRT) with stereotactic body radiation therapy (SBRT) for definitive treatment of prostate cancer patients. Patients and methods Between February 2018 and August 2019, 205 low-, intermediate- and high-risk prostate cancer patients were treated with SBRT using “CyberKnife M6” linear accelerator. In low-risk patients 7.5–8 Gy was delivered to the prostate gland by each fraction. For intermediate- and high-risk disease a dose of 7.5–8 Gy was delivered to the prostate and 6–6.5 Gy to the seminal vesicles by each fraction with a simultaneous integrated boost (SIB) technique. A total of 5 fractions (total dose 37.5–40 Gy) were given on every second working day. Acute radiotherapy-related genitourinary (GU) and gastrointestinal (GI) side effects were assessed using Radiation Therapy Oncology Group (RTOG) scoring system. Results Of the 205 patients (28 low-, 115 intermediate-, 62 high-risk) treated with SBRT, 203 (99%) completed the radiotherapy as planned. The duration of radiation therapy was 1 week and 3 days. The frequencies of acute radiotherapy-related side effects were as follows: GU grade 0 – 17.1%, grade I – 30.7%, grade II – 50.7%, grade III – 1.5%; and GI grade 0 – 62.4%, grade I–31.7%, grade II–5.9%, grade III–0%. None of the patients developed grade ≥ 4 acute toxicity. Conclusions SBRT with a total dose of 37.5–40 Gy in 5 fractions appears to be a safe and well tolerated treatment option in patients with prostate cancer, associated with slight or moderate early side effects. Longer follow-up is needed to evaluate long-term toxicity and biochemical control.

Analysis of Applicator Insertion Related Acute Side Effects for Cervical Cancer Treated With Brachytherapy

PurposeTo report applicator insertion-related acute side effects during brachytherapy (BT) procedure for cervical cancer patients.Materials and MethodsBetween November 2017 and December 2019, 407 BT fractions were performed in 125 patients with locally advanced cervical cancer. Acute side effects recorded comprised anesthesia-related side effects, mechanical-related side effects and infection, whose frequency and degree were recorded. Pain was assessed using numeric rating scale; vaginal bleeding volume was counted by weighing gauze pieces used in packing. The BT procedure comprised eight stages: anesthesia, applicator insertion, image acquisition, transport, waiting for treatment, dose delivery, applicator removal, and removed which denoted 0.5–12.0 h period after removal, with time of each stage recorded. Factors influencing acute side effects were assessed by Spearman correlation and Mann–Whitney U test.ResultsThe most common acute side effect was pain, followed by vaginal bleeding. The mean scores for pain were highest during removal time, 4.9 ± 1.6 points. The mean vaginal bleeding volume was 44.4 ml during removal time. Mean total procedure time was 218.8 (175–336) min, having positive relationship with frequency of acute side effects. The total procedure time with acute side effects was longer than that without acute side effects. The longest procedure time was waiting time, 113.0 (91.0–132.0) min. More needles generated higher pain scores and larger volume of vaginal bleeding.ConclusionPain and vaginal bleeding were the most common acute side effects, especially during removal time, which physicians should focus on. Shortening patients’ waiting time helps to reduce the total procedure time, thus, reduce acute side effects. While meeting dose requirement, less needles are helpful to reduce acute side effects.

Effectiveness and tolerability of radiotherapy for patients with indolent non-Hodgkin's lymphoma - a monocenter analysis

Purpose To analyze the effectiveness and toxicities of radiotherapy in indolent non-Hodgkin's lymphoma (iNHL) patients treated in our institution. Material and Methods Patients with iNHL treated with radiotherapy between 1999 and 2016 were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were local control (LC), overall survival (OS) and toxicities. PFS, LC, and OS were analyzed using Kaplan-Meier method. Log-rank test was used to investigate the differences between subgroups. Cox proportional hazard model was used for univariate continuous analysis.Results Seventy-five patients were identified in our institutional database between 1999 and 2016. Fifty-eight (77.3%) had stage I after Ann-Arbor and 17 patients (22.7%) had stage II. The median follow-up was 87 months (95%-CI: 72 – 102 months). Median single dose per fraction was 2.0 Gy (range, 1.5 – 2 Gy) and median total dose was 30.6 Gy (range, 16 – 45 Gy). Radiotherapy was performed in 2D (n = 10; 13.3%), 3D (n = 63; 84.0%) and VMAT (n = 2; 2.7%) techniques, respectively. The median PFS was 14.0 years (95%-CI: 8.3 – 19.7 years). The estimated PFS after 5 and 10 years were 73.0% and 65.5% in Kaplan-Meier analysis, respectively. The 5- and 10- year LC were 94.9% and 92.3%, respectively. The 5- and 10-year OS were 88.6% and 73.9%. In univariate analyses of PFS, younger patients (≤ 60 years old) had significantly superior PFS to those older than 60 years old (5-year PFS 81.9% vs. 65.1%, p= 0.021). Dose escalation >36.0Gy had no prognostic influence in term of PFS (p= 0.543). Extranodal involvement, stage and histology had no prognostic impact on PFS. Depending on the site of lymphomas, the most common acute side effects were: dermatitis CTCAE °I - II (8.0%), xerostomia CTC °I (8.0%), cataract CTC °I (12.0%) and dry eyes CTC °I - II (14.6%). No adverse event CTC° III was reported. Most acute side effects recovered at 3 to 6 months after radiotherapy except for CTC °I cataract and xerostomia. Conclusion Local Radiotherapy was highly effective for treatment of early stage iNHL with no serious side effects in our cohort. The most acute CTCAE °I – II side effects recovered 3 to 6 months later. Technique advances seem to have further improved effectiveness and tolerability of radiotherapy. Trial registration: Local ethics committee of Ludwig-Maximilian-University (LMU) Munich approved this retrospective analysis on the May 7th, 2019 (Nr. 19-137).

Formulary

This chapter describes the drugs most commonly used in pre-hospital care. As a result, it is restricted to indications which are likely to be encountered in the pre-hospital management of patients and only describes formulations which are used in these circumstances. For example, the use of oral amiodarone is not discussed, neither is the use of oral steroids in the management of chronic inflammatory conditions, although intravenous steroids in acute asthma and anaphylaxis are mentioned. Significant acute side-effects are listed.

THERAPEUTIC MECHANISMS OF KETAMINE

Major depressive disorder is the greatest burden of developed countries in the context of morbidity caused by mental disorders. Until recent, ketamine has been mostly used for anesthesia, analgesia, sedation and treatment of chronic pain syndromes. However, unique pharmacodynamic properties of ketamine have increased interests in it's use for treatment of depression. It is assumed that ketamine reverses synaptic chronic stress pathology within one day of administration by postsynaptic glutamate activation, providing synaptic connectivity restoration that last for days or weeks. Potential glutamatergic agents, in context of treatment of major depressive disorder are not entirely novel phenomenon. Considering the aforementioned, current neurobiological view of depression as a solely monoaminergic phenomenon should be reassessed in order to prompt discovery of putative antidepressant drugs of novel generation. Acute side effects, such as increased salivation, increase in heart rate, systemic arterial pressure and intracranial pressure necessitate careful monitoring during intravenous administration of ketamine, even in subanesthetic doses. However, major burden of ketamine administration lies in it's ability to produce psychotomimetic side effects and emergence delirium. Esketamine nasal spray has now been widely approved and is considered safe in terms of acute side effects, tolerability and consistent therapeutic benefit.