Efficacy Of Low-dose Radiotherapy Research Articles

Low-dose radiotherapy for greater trochanteric pain syndrome—a single-centre analysis

PurposeTo determine predictive factors associated with a good response (GR) to and efficacy of low-dose radiotherapy (LDRT) in patients with greater trochanteric pain syndrome (GTPS).MethodsPatients with GTPS were irradiated on a linear accelerator with 0.5–1.0 Gy per fraction to a total dose of 3.0–4.0 Gy per series. The endpoint was subjective good response (GR) to treatment 2 months after completion of the last LDRT series, defined as complete pain relief or marked improvement assessed using the von Pannewitz score. A positive response to steroid injection (SI) was defined as pain relief of at least 7 days. Patient and treatment-related characteristics were evaluated with respect to LDRT outcomes.ResultsOutcomes were assessed for 71 peritrochanteric spaces (PTSs; 65 patients, 48 females, with mean age of 63 [44–91] years). Prior SI had been given to 55 (77%) PTSs and 40 PTSs received two series of LDRT. Two months after completion of LDRT, GR was reported in 42 PTSs (59%). Two series of LDRT provided a significantly higher rate of GR than one series (72.5 vs. 42% PTSs, p = 0.015). Temporary pain relief after prior SI predicted GR to LDRT compared with PTSs which had not responded to SI (73 vs. 28% PTSs, p = 0.001). A regional structural abnormality, present in 34 PTSs (48%), was associated with a reduction of GR to LDRT (44 vs. 73% PTSs, p = 0.017).ConclusionLDRT is an effective treatment for GTPS. Administration of two LDRT series, prior response to SI, and absence of structural abnormalities may predict significantly better treatment outcomes.

Evaluating the Efficacy of Low Dose Radiotherapy in the Treatment of Painful, Benign Musculoskeletal Conditions

Introduction: Inflammatory diseases of the locomotor system are a very heterogeneous group of ailments, including enthesopathies. They arise as a result of long-term overload in the area of tendon attachments, which may lead to chronic inflammation and then, degeneration, which are the cause of chronic pain. The main methods of treatment are physiotherapy, physical agents treatment, pharmacological and orthopaedic treatment, i.e. manual therapy, the use of appropriate insoles correcting posture defects, cryotherapy, shock waves, iontophoresis, non-steroidal anti-inflammatory drugs, steroid injections, surgery and platelet-rich plasma therapy. Another, lesser-known method of treatment is low-dose radiation therapy (LDRT). Research objective: To evaluate the efficacy, time to improvement and analgesic effect duration after low dose radiotherapy (LDRT) in patients with enthesopathies. Materials and methods: A retrospective analysis included a group of 90 patients (51 women, 39 men) with a diagnosis of enthesopathy and treated with conformal radiotherapy using photon radiation at the NIO in Kraków from July 2018 to April 2021. The treated group included patients with heel, elbow, knee, shoulder and wrist problems. In each case, the total dose of radiation was 6 Gy, divided into 6 fractions administered on subsequent working days, given in a vacuum form to the patient immobilised. Pain was assessed with the use of an 11-point numerical rating scale (NRS). Pain was assessed by implementing the above mentioned scale prior to the commencement of radiotherapy, during the treatment, and then 1 month and 6 months following the completion of treatment. Results: In the vast majority of patients (92%), with a mean age of 51 years, at least temporary, partial improvement of pain has been demonstrated in the irradiated joints. The median time to treatment response was 30 days. Median pain intensity, as measured via the NRS scale, was 8.0 (IQR 7.0-10.0) before the treatment, 5.0 (IQR 3.0-7.0) after 1 month, and 2.0 (IQR 0-4.0) after 6 months from treatment completion. Persistent improvement in pain control after LDRT was shown in 85% of patients, with a mean follow-up period of 522 days (range: 55-952 days). The best response was observed in patients with heel spurs (a decrease of median NRS score by 7.0). Conclusions: Low dose RT is a very effective method of pain reduction in enthesopathies, particularly among patients with heel spurs. Most patients experienced pain reduction as early as 1 month after LDRT. Continuous pain reduction was observed during the follow-up period up to the 6th month and in most cases, the analgesic effect was long-lasting.

Efficacy of low-dose radiotherapy (2 Gy × 2) in the treatment of marginal zone and mucosa-associated lymphoid tissue lymphomas.

Objectives:To investigate the efficacy of a schedule of low-dose radiotherapy (LDRT) with 4 Gy (2 Gy x 2) in a cohort of unselected MALT or MZL patients.Methods:We retrospectively collected all patients receiving LDRT, either for cure or palliation, for a stage I–IV histologically proven MALT or MZL between 2016 and 2020. Response to LDRT was evaluated with the Lugano criteria. Local control (LC), distant relapse-free survival (DRFS), progression-free survival (PFS) and overall survival (OS) were stratified for treatment intent (curative vs palliative) and estimated by the Kaplan-Meier product-limit.Results:Among 45 consecutively enrolled patients with a median age of 68 years (range 22–86), 26 (58%) were female. Thirty-one patients (69%) with a stage I–II disease received LDRT as first line therapy and with a curative intent. Overall response rate was 93%, with no significant difference among curative and palliative intent. With a median follow-up of 18 months, LC, DRFS, PFS and OS at 2 years were 93, 92, 76 and 91%, respectively, in the overall population. Patients receiving curative LDRT had a better PFS at 2 years (85% vs 54%, p < 0.01) compared to patients receiving palliative treatment. LDRT was well tolerated in all patients, without any significant acute or chronic side-effect.Conclusions:LDRT is effective and well tolerated in patients affected with MALT or nodal MZL, achieving high response rates and durable remission at 2 years.Advances in knowledge:This study shows the efficacy of LDRT in the treatment of MALT and MZL.

Low-dose ultra-fractionated radiotherapy as a chemosensitizer of neoadjuvant chemotherapy for locally advanced nasopharyngeal carcinoma: A preliminary results of the phase II trial.

e18022 Background: The main failure model of locally advanced nasopharyngeal carcinoma (LA-NPC) is local failure and distant metastasis. N stage is a prognostic factor for NPC. Some characteristics of lymph nodes, such as the size, number, laterality, extra-nodal neoplastic spread and central necrosis, were the high-risk factors for treatment failure. Nowadays, neoadjuvant chemotherapy followed with CCRT was recommended for LA-NPC patients. Low-dose radiotherapy (LDRT), which is &lt; 100cGy, induces enhanced cell killing in vitro and in vivo by the hyper-radiation sensitivity phenomenon and potentiates effects of chemotherapy. Few studies reported about it. Recently, a single arm study showed it could improve the ORR to 82% for head and neck squamous carcinoma when combined with neoadjuvant chemotherapy. So, we aimed to investigate the efficacy of LDRT combined with neoadjuvant chemotherapy for high-risk LANPC. Methods: Squamous III-IVA NPC patients (UICC/AJCC 8th) with high-risk factors of lymph nodes were prospectively enrolled in the study. The high-risk factors should include one of these followings: lymph node with central necrosis, extranodal neoplastic spread, contrast-enhancing rim or the shortest diameter of lymph nodes ≥3cm. 3 cycles of neoadjuvant chemotherapy were given, the regimen was docetaxel (75mg/m2 D1) and cisplatin (75mg/m2 D1). LDRT was delivered as 50cGy per fraction twice a day for gross nodal disease on D1 and D2 of neoadjuvant chemotherapy. All the patients received MRI scan before and after the neoadjuvant chemotherapy. Propensity score matching was used to select the patients as control group. RECIST criteria was used to evaluate the ORR. Results: From Jun 2020 to Jan 2021, a total of 27 patients were enrolled in the study. Another 27 patients were matched for control group. For the whole patients, the median age were 43 years. III and IVA Clinical stage were 25.9%, 74.1% and 29.6%, 70.4% respectively for LDRT and control group (p = 0.761). As for the lymph nodes, the ORR of LDRT group was significantly higher than control group (100% vs 85.2%, p = 0.038). The average regression rate of lymph nodes was 89.4% in LDRT group, CR and PR was 7.4% and 92.6%. However, the average regression rate of it was only 56.24% in control group. There was no CR, PR and SD were 88.9% and 11.1%. For the primary tumor, there was no significant difference. But we found the ORR of it was higher in LDRT group (96.3% vs 81.5%, p = 0.083). And the average regression rate was 57.5% and 38.3% respectively in LDRT and control group. Conclusions: LDRT combined with neoadjuvant chemotherapy could improve the ORR for primary tumor and lymph nodes in high-risk LANPC patients, especially for lymph nodes. This new treatment model could be a promising strategy to improve LC, and needed to be confirmed in the future practice.

Efficacy of Low Dose Radiotherapy in Head & Neck MALT Lymphoma

Efficacy of Low Dose Radiotherapy in Head & Neck MALT Lymphoma

Ongoing Trials of Low Dose Radiation Therapy for Covid-19 Pneumonia: Studying the Past to Define the Future?

The current COVID-19 pandemic, caused by the infection by the SARS-CoV-2 virus, is a disease with great contagiousness, a non-negligible morbidity rate and a very important consumption of health resources, which is leading to a blockade of practically the entire world health system. The main complication is pneumonia, which has an important inflammatory component and for which there is still no definitive treatment. The absence of a standardized treatment coupled with the possible failure in the supply of drugs due to the great existing demand makes it necessary to investigate new anti-inflammatory therapeutics. The anti-inflammatory efficacy of Low-Dose Radio Therapy (LD-RT) has been confirmed in several experimental models, both in vitro and in vivo, as well as in different clinical studies. The radiobiological mechanisms that confirm this claim are becoming increasingly well known. Unlike high-dose radiotherapy that induces the production of pro-inflammatory cytokines in immune and endothelial cells, low doses of radiotherapy (0.5-1.5 Gy) act on the cells that participate in the inflammatory response, producing anti-inflammatory effects. At this time, there are different clinical studies underway that seek to demonstrate the usefulness of LD-RT against COVID19 pneumonia and open the possibility of offering an effective and widely affordable therapeutic alternative for this infection. Perhaps, as Confucius wrote, it is necessary to “study the past if you would define the future”

Repeated courses of low-dose 2×2Gy radiation therapy in patients with indolent B-cell non-Hodgkin lymphomas.

PurposeIn patients with indolent B‐cell non‐Hodgkin's lymphoma (B‐NHL), one course of low‐dose radiotherapy (LD‐RT) 2 × 2 Gy is emerging as new option of therapy in palliative setting. Efficacy of LD‐RT when repeated remains to be determinate. This study aims to assess the efficacy of repeated LD‐RT given in patients with indolent B‐NHL.Materials and MethodsAll consecutive adult patients who received two or more courses of LD‐RT 2 × 2 Gy for indolent B‐NHL at Gustave Roussy institution, during the period 1990‐2015 were retrospectively investigated.ResultsThirty‐three patients received two or more courses of LD‐RT for indolent B‐NHL during the study period. The median age was 57 (range 37‐80) years, histological types were distributed among follicular lymphoma (n = 24 pts; 73%), marginal‐zone lymphoma (n = 6 pts; 18%), and primary cutaneous follicle center lymphoma (n = 3 pts; 9%). The median number of low‐dose radiation therapy courses given per patients was 2 (range 2‐6). The overall response rates following the first and the second course of LD‐RT were 96% and 88%, respectively (P = .31). The 1‐ and 2‐years local control rates following the first courses of LD‐RT were 94% (CI 95: 86‐100) and 94% (CI 95: 86‐98); and were 91% (CI 95: 82‐100) and 88% (CI 95: 77‐100) following the second course of LD‐RT (P = .39).ConclusionThe repeated courses of LD‐RT offered similar efficacy compare with the first course in patients with indolent B‐NHL. LD‐RT repeated is a simple, easy to give, and non‐toxic asset that could be investigated as treatment option in patients with indolent B‐NHL.

Reduction of some extra-articular complications associated with arthritis development in rats by low dose γ-irradiation

Rheumatoid arthritis (RA) is considered a systemic inflammatory disease that affects not only the joints but also other organs in the body causing many extra-articular complications. Low-dose radiation (LDR) modulates a variety of immune responses that have exhibited the properties of immune hormesis. LDR has been used clinically for the treatment of autoimmune diseases. Several molecular mechanisms and cellular components contribute to the clinical efficacy of low dose radiotherapy (LD-RT). The present study aimed to evaluate the possible capability of low dose γ-irradiation to reduce some of these extra-articular complications in adjuvant-induced arthritis model in rats. Our results revealed a significant increase in liver parameters in serum including ALT, AST activities as well as creatinine level in adjuvant induced arthritic rats that indicate liver and kidney impairment respectively. Results also revealed sharp increase in total leukocytic count (TLC). All of these biochemical and hematological disturbances were found to be significantly improved after exposure to low dose γ-irradiation. Keywords: Rheumatoid arthritis, extra-articular complications, adjuvant induced arthritis, low dose γ-irradiation

Therapy of nodal Follicular Lymphoma (WHO grade 1/2) in clinical stage I/II using response adapted Involved Site Radiotherapy in combination with Obinutuzumab (Gazyvaro) - GAZAI Trial (GAZyvaro and response adapted Involved-site Radiotherapy): a study protocol for a single-arm, non-randomized, open, national, multi-center phase II trial

BackgroundLarge field irradiation had been standard for early-stage follicular lymphoma (FL) for a long time. Although involved field radiotherapy (IF-RT) was recently favored because of the toxicity of large field irradiation, smaller irradiation fields have been accompanied with an increased risk of out-of-field recurrence. The MIR (MabThera® and Involved field Radiation) trial has shown that the combination of IF-RT at a dose of 30–40 Gy with the anti-CD20 antibody rituximab has led to similar efficacy compared with large field irradiation but with markedly reduced side effects. Immune modulating radiation therapy alone using low-dose radiotherapy (LDRT) of 2 × 2 Gy has been shown to be effective in FL. The GAZAI (GAZyvaro and response Adapted Involved-site Radiotherapy) trial aims to prove the efficacy of LDRT in combination with a novel anti-CD20 therapy.Methods/designThe GAZAI trial is a non-randomized, open, non-controlled, German, multi-center phase II trial that includes patients with early-stage (I and II) nodular FL (grades 1 and 2) confirmed by central histological review. A maximum of 93 patients will be included in the trial. Patients will receive a combined approach of immunotherapy with the fully humanized anti-CD20 antibody obinutuzumab (Gazyvaro®) and involved site radiotherapy (IS-RT) with 2 × 2 Gy. The primary endpoint of the trial is the rate of metabolic complete response (CR), based on fludeoxyglucose positron emission tomography/computed tomography, after obinutuzumab and 2 × 2 Gy IS-RT in week 18. Secondary endpoints are morphologic CR rate in weeks 7 and 18 and month 6, progression-free survival, toxicity, recurrence patterns, overall survival, and quality of life. Additionally, minimal residual disease response is assessed. The risk for a potentially higher recurrence rate after LDRT will be minimized by additional salvage radiation up to the “full dose” of 40 Gy for patients who have less than a metabolic CR and morphologic partial response/CR, which will be evaluated in week 18, offering a response-adapted approach.DiscussionThe goal of this trial is a further reduction of the radiation dose in patients with nodal early-stage FL showing a good response to a combination of LDRT and anti-CD20 immunotherapy and a comparison with the currently published MIR trial.Trial registrationEudraCT number: 2016-002059-89. ClinicalTrials.gov identifier: NCT03341520.

Radiotherapy for calcaneodynia, achillodynia, painful gonarthrosis, bursitis trochanterica, and painful shoulder syndrome - Early and late results of a prospective clinical quality assessment

BackgroundThe aim of this prospective clinical quality assessment was to evaluate the short-term and long-term efficacy of low dose radiotherapy (RT) for calcaneodynia, achillodynia, painful gonarthrosis, painful bursitis trochanterica, and painful shoulder syndrome.MethodsBetween October 2011 and October 2013, patients with calcaneodynia, achillodynia, painful gonarthrosis, painful bursitis trochanterica, and painful shoulder syndrome were recruited for this prospective clinical quality assessment. Single doses of 0.5-1.0 Gy and a total dose of 6.0 Gy per series were used. Pain was measured before and directly after RT (early response) with a visual analogue scale (VAS). Additionally, pain relief was measured with the four-scale pain score according to “von Pannewitz” (VPS) immediately at the end of RT and during follow-up. Within this context we defined a good response as complete pain relief and markedly improved. The assessment of the long-term efficacy was carried out by a telephone survey.Results703 evaluable patients (461 female, 242 male) with a mean age of 63.2 years (28-96) were recruited for this prospective clinical quality assessment. In 254 patients RT was performed with the linear accelerator, 449 patients received orthovoltage radiotherapy. After a median follow-up of 33 months (3-60) 437 patients could be reached for evaluation of follow up results. The mean VAS value before treatment was 6.63 (1.9-10) and immediately on completion of RT 4.51 (0-10) (p < 0,001). Concerning the VPS immediately on completion of RT, a good response could be achieved in 264/703 patients (37.6%), and with the follow up in 255/437 patients (58.4%) (p < 0.001). Only in patients with gonarthrosis we could not observe a significantly improved long-term success in comparison to the results immediately after RT (30.2% versus 29.9%).ConclusionLow dose RT is a very effective treatment for the management of calcaneodynia, achillodynia, painful gonarthrosis, painful bursitis trochanterica, and painful shoulder syndrome. Due to the delayed onset of analgesic effects low dose RT results in a significantly improved long-term efficacy in comparison to the results immediately after RT particularly in patients with calcaneodynia, achillodynia, bursitis trochanterica, and shoulder syndrome.

EP-1429: maintaining efficacy of low-dose radiotherapy on pain and function in degenerative skeletal diseases

EP-1429: maintaining efficacy of low-dose radiotherapy on pain and function in degenerative skeletal diseases

PO-0666: Comparing the efficacy of low-dose radiotherapy in patients with aggressive and indolent lymphomas

PO-0666: Comparing the efficacy of low-dose radiotherapy in patients with aggressive and indolent lymphomas

Efficacy of low dose radiotherapy for primary orbital marginal zone lymphoma

Marginal zone lymphoma (MZL) is a radiosensitive tumor, with high local control (LC) rates with moderate dose radiotherapy (RT). This retrospective study, performed at the Peter MacCallum Cancer Centre, evaluated the efficacy and toxicity of patients with orbital MZL treated to 24–25 Gy. Twenty-four patients (27 orbits) were identified, with median follow-up of 41 months. Disease was conjunctival in 16 orbits (59%), lacrimal in seven (26%), in the eyelid in one (4%) and elsewhere in three (11%). All patients attained a complete response. Three patients had treatment failures: one local relapse, one contralateral and one distant relapse. Freedom from local failure, freedom from progression, progression-free survival and overall survival were 100%, 90%, 90% and 100% at 2 years and 92%, 81%, 81% and 100% at 5 years, respectively. Aside from cataractogenesis, there was no significant late toxicity. Our study shows that RT doses of 24–25 Gy provide high rates of LC for orbital MZL with acceptable morbidity.

Activator protein 1 shows a biphasic induction and transcriptional activity after low dose X-irradiation in EA.hy.926 endothelial cells

Low dose radiotherapy (LD-RT) is known to exert an anti-inflammatory effect. The underlying molecular mechanisms, however, are still a matter of actual research. We have recently shown that LD-RT of stimulated EA.hy.926 endothelial cells (EC) resulted in a biphasic DNA-binding and transcriptional activity of NF-κB in parallel with a biphasic course of leukocyte adhesion. Here we report, that following low dose X-irradiation, an increased activator protein 1 (AP-1) DNA-binding activity was observed in EC with a first relative maximum at 0.3 Gy as analysed by electrophoretic mobility shift assay. AP-1 activity then decreased at doses between 0.5 and 1 Gy and subsequently increased again at 3 Gy. This biphasic profile was confirmed on the transcriptional level by an AP-1 specific chemoluminescence reporter assay. In conclusion, the discontinuous dose response of AP-1 activation may add a further facet to the plethora of mechanisms contributing to the anti-inflammatory efficacy of LD-RT.

Effects of low dose radiation therapy on adjuvant induced arthritis in rats

Purpose : Substantial clinical evidence shows the efficacy of low dose radiotherapy (RT) in the treatment of painful osteoarthritis. Experimental investigations into these empirically clinical observations remain scarce. This study investigated in vivo the effects of daily 5 1.0Gy versus 5 0.5Gy on adjuvant induced arthritis in rats in order to explore whether there is a dose dependence of anti-inflammatory efficacy. Materials and methods : Adjuvant arthritis in female Lewis rats was induced by intradermal injection of heat inactivated Mycobacterium tuberculosis on day 0. Both hind paws were X-irradiated daily from days 15 to 19 after induction according to four protocols (15 animals/group): group 1, 5 1.0Gy (non-arthritic animals); group 2, sham-irradiated control; group 3, 5 1.0Gy; group 4, 5 0.5Gy. The clinical parameters arthritis score (AS), hind paw volume (HPV), body weight, and erythrocyte sedimentation rate (ESR) were determined. On days 21 and 30 histological sections of at least 12 ankle joints per group were analysed semi-quantitatively. Results : Local irradiation of non-arthritic rats (group 1) with 5 1 Gy did not induce any arthritic signs. Sham-irradiated arthritic rats (group 2) showed a full-blown arthritic syndrome. Treatment of arthritic rats with 5 1 Gy (group 3) or 5 0.5Gy (group 4) led to a reduction of mean AS from day 21 to 29 compared with group 2 (days 27-29-group 3: p =0.037; group 4: p =0.034), with no differences in efficacy between groups 3 and 4. Concurrently, following radiation treatment there was no further increase in HPV. At the end of the observation period, this effect demonstrated a dose-dependent level of significance (days 27-29-group 3: p =0.0036; group 4: p =0.039). A significant decrease in the ESR was noted in both irradiated arthritic groups on day 21 (group 3: p =0.015; group 4: p =0.006). The histopathological analysis revealed a highly significant reduction of cartilage and bone destruction on day 30 in both irradiated groups. Conclusions : This study confirms by objective criteria the anti-iinflammatory efficacy of low dose RT and gives some indication for a dose dependence of its efficacy.

Mechanisms of the anti-inflammatory activity of low-dose radiation therapy

Purpose: To investigate the hypothesis that modulation of the function of activated macrophages is one of the mechanisms of the clinically observed anti-inflammatory and analgesic efficacy of low-dose radiotherapy in the treatment of a variety of painful joint diseases with total doses between 1 and 6Gy. Materials and methods: Metabolic activity, cell proliferation, reproductive integrity, nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression by unstimulated or LPS/ gamma -IFN-stimulated macrophages in vitro was investigated at different times after radiation doses ranging from 0.3Gy to 10Gy. In vivo, chronic granulomatous air pouches were induced in mice and either sham treated or irradiated with 2Gy on day 2 or day 6, or with five daily doses of 0.5Gy. On day 7, the iNOS expression was assessed by Western blot and localized by immuno-histochemistry in cryostat sections. Results: In stimulated macrophages, metabolic activity, proliferation and reproductive integrity were not a ffected by radiation doses up to 10Gy since they are apparently irreversible postmitotic cells. However, a dose-dependent modulation of the NO pathway was observed with significant inhibition by the low radiation doses used in anti-inflammatory radiotherapy but with super-stimulation by the high radiation doses used in cancer therapy. Conclusions: The empirically based anti-inflammatory radiotherapy of benign diseases appears to act through specific modulation of different pathways of inflammatory reactions such as the nitric oxide pathway in stimulated macrophages.