Gy In Single Fraction Research Articles

Abstract 533: The immune landscape in colon cancer and its changes after radiotherapy

Abstract Background: The TRANSLATE project started in 2016 to test the immune effects on circulating immune cells and cytokines of metronomic Cyclophosphamide (CTX), daily low-dose IL-2 administered every other week, and radiotherapy (RT). The rationale is based on self vaccination induced by RT, T cells expansion by IL-2 treatment and selective Tregs down regulation by low dose cyclophosphamide administration. Materials/Methods: Treatment consisted of CTX 50/mg tab daily continuously until progression or unacceptable toxicity, 8 Gy single fraction on one metastatic lesion given day 8 from CTX start and IL-2, 500.000 UI twice a day i.v. day 1 to 5 every other week, starting the day after RT. We enrolled patients with end-stage for colon, breast, kidney and prostate cancer. Analysis was performed at baseline, the day after RT, after 28 days from treatment start and at disease progression. Assay focused on Tregs, CD8+, NK, MDSC, CD3-PD1, IL-2, IL-4, IL-5, IL- 6, IL-10, IL-12, IL-13, IL-17a, TNFα, IFNγ, TGFβ. We report baseline and post-RT data separately in patients with colon cancer (CC) and other patients (non-CC). Results: We report data from 8 pts with left colon, 6 with breast, 2 with kidney and 3 with prostate cancer. At baseline, cytokine expression was similar in CC and non-CC except IFNγ and IL-13, both less represented in CC. After RT, TNFα increased in both groups, but more evidently in CC. A clear increase in IL-10 and IFNγ occurred only in non-CC, while IL-2 increased only in CC. Cumulatively, CC and non-CC reacted differently to RT in terms of positive or negative changes of the analyzed cytokines. On the contrary, we did not observe clear differences in immune cells between CC and non-CC neither at baseline nor after RT. Discussion: The limited number of patients reduced the interpretation of the study. The differences observed are numerical, but not statistically significant. Colon cancer shows some peculiarities, including the low IL-13 and IFNγ value and a different response to RT. Further analyses investigations are in progress. Citation Format: Cristiana Lo Nigro, Dario Sangiolo, Vincenzo Ricci, Ornella Garrone, Andrea Abbona, Antonella Falletta, Anna Merlotti, Chiara Varamo, Massimo Aglietta, Loretta Gammaitoni, Oscar Bertetto, Marco Merlano. The immune landscape in colon cancer and its changes after radiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 533.

Adipose-Derived Stem Cell Therapy Ameliorates Ionizing Irradiation Fibrosis via Hepatocyte Growth Factor-Mediated Transforming Growth Factor-β Downregulation and Recruitment of Bone Marrow Cells.

Radiation therapy to anatomic regions, including the head and neck, chest wall, and extremities, can produce radiation-induced fibrosis (RIF). To elucidate the cellular and molecular mechanism(s) involved in RIF, female C57BL/6J mice were irradiated to the right flank to 35 Gy in single fraction using 6 Mv electrons. Radiation fibrosis was detected by day 14, was increased by day 28, and confirmed by Masson's trichrome histological staining for collagen. Biopsied tissue at day 14 showed an increase in expression of fibrosis-related genes including transforming growth factor-β (TGF-β) and collagens 1-6. A single adipose-derived stem cell (ASC) injection on day 28 at the irradiated site decreased by day 40: epithelial thickness, collagen deposition, and significantly improved limb excursion compared with irradiated controls. Noncontact transwell coculture of ASCs above a monolayer of irradiated human foreskin fibroblasts downregulated fibrosis-related genes TGF-β, connective tissue growth factor, interleukin-1, NF-kB, tumor necrosis factor, and collagens 1-6. Hepatocyte growth factor (HGF) secreted by ASCs was identified as a novel mechanism by which ASCs exert antifibrotic effects by downregulating fibrotic gene expression in irradiated cells and recruiting bone marrow cells to the irradiated site. In conclusion, these data indicate a mechanistic role of HGF secreted by ASCs in reducing RIF. Stem Cells 2019;37:791-802.

Symptom Palliation in Patients with Bone Metastases Treated with Radiotherapy

Abstract Context: Skeleton is the most common organ affected by metastases. Bone pain is the most common symptom of metastatic bone disease. The treatment of bone metastasis is primarily palliative requiring multidisciplinary therapies; radiotherapy (RT), however, remains the cornerstone of the treatment. Aims: The aim of this study is to measure the effectiveness of RT in terms of symptomatic relief in pain and insomnia, improvement in stability/movement, and decrease in the requirement of analgesics by patients using the Hundred Paisa Pain Scale. Subjects and Methods: The RT records of 226 patients with bone metastasis treated at the department of Radiotherapy, SMS Medical College, Jaipur; from July 2015 to December 2016 over cobalt-60 teletherapy unit were analyzed. The RT dose fractionation ranged from 30 Gy in 10 daily fractions, 20 Gy in 5 daily fractions, 12.5 Gy in 2 weekly fractions, and 8 Gy in single fraction. Results: The median age of the cohort was 54 (range, 29–84) years. The most common site of primary tumor was lung (30.1%), followed by breast (12.4%) and prostate (11.9%). The most common bone involved was vertebrae (71.2%), followed by pelvis (14.6%); among vertebrae, thoracic vertebrae were most commonly involved (63.9%), followed by lumbar vertebrae (57.8%). The maximum relief in pain was seen with 6.25 Gy/fraction schedule, whereas the maximum improvement in stability/movement was noted with 3 Gy/fraction schedule. The 8 Gy single-fraction schedule was associated with maximum relief in insomnia and decrease in analgesic requirement. Conclusion: The current institutional protocol of weekly hypofractionated palliative RT of 6.25 Gy per fraction up to a maximum of four fractions given on Saturday has shown results comparable with other schedules with well tolerance and achievement of acceptable symptom palliation. This weekly schedule is practically convenient to both the patients who mostly came from far-flung areas and the institute as it spares the already overburdened machine to carry on conventional RT from Monday to Friday.

Late toxicity after single dose HDR prostate brachytherapy and EBRT for localized prostate cancer: Clinical and dosimetric predictors in a prospective cohort study

PurposeTo describe the genitourinary (GU) and gastrointestinal (GI) late toxicity profile and to analyse the clinical and dosimetry outcomes predictors of the combination of EBRT and high-dose-rate (HDR) prostate brachytherapy (BT) for localized prostate cancer. Materials and methodsBetween January 2012 and May 2017, 210 patients were included in a prospective protocol. Treatment consisted in HDR-BT (15 Gy single fraction) plus 3DCRT (37.5 Gy/15 fractions). Univariate and multivariate logistic regressions were used to analyse the impact of variables on late toxicity. ResultsMedian age was 71 (56–82), 12.4% of patients had low, 44.3% intermediate and 41% high-risk prostate cancer. Median prostate volume was 28.4 cc. Median V100, V150, V200 were 98.2%, 27% and 7.4% respectively. Median urethra Dmax, rectum D1cc and D2cc, were 113.5%, 62.2%% and 54.2% respectively.After a median follow-up of 41 months (5–75) late G2 GU and GI late toxicity was observed in 14.8% and 5.2% of patients respectively. Late G3 GU and GI toxicity occurred in 0% and 1% of patients respectively.There were no outcome correlations with late G ≥ 2 GU toxicity on univariate analysis. Previous cardiovascular comorbidity (p = 0.042), and dose to the rectum D2cc (p = 0.016) and D1cc (p = 0.017) were associated with G ≥ 2 GI toxicity.Multivariate analysis showed that rectum D1cc (HR11.56; 95%CI 1.4–92.1; p = 0.021) and prior history of cardiovascular disease (HR3.6; 95%CI 1–12.9; p = 0.045) remained independent predictors of G ≥ 2 GI toxicity. ConclusionsThere is a low incidence of late GU and GI morbidity using single fraction HDR-BT and hypofractionated EBRT. Previous cardiovascular disease and dose to the rectum were observed to correlate with GI toxicity.

Single institution experience treating adrenal metastases with stereotactic body radiation therapy.

The objective of the study is to present our experience of treating adrenal metastases using stereotactic body radiation therapy (SBRT). We retrospectively reviewed patients with adrenal metastases treated using SBRT from 2001 to 2014. Response Evaluation Criteria in Solid Tumors v1.1 was used. Maximum tumor response was defined as the greatest percentage tumor reduction noted on two or more post-SBRT CT scans. We identified 44 patients (median age 61.3 years, range: 25.8-85), with 54 adrenal metastases; primary diagnoses include non-small cell lung cancer (28 patients and 38 lesions), small cell lung cancer (1 patient), hepatocellular carcinoma (6 patients), and other (9 patients). Treatment was delivered in single (16 lesions, median dose 18 Gy [14-18]) or multiple fractions (38 lesions, median dose 30 Gy [16-40]). Median planning target volume was 49.65cc (3.21-984.54). Median response at first post-SBRT follow-up (median 1.65 months (m) (0.33-5.37), n = 46 lesions) was 10.8% with 91.3% local control. Median maximum tumor response was 31.8% (n = 32 lesions) at median follow-up of 5.4 m (0.9-44.8) with 96.6% local control. The response was comparable regardless of tumor histology or treatment fractionation. No patients experienced Grade 3/4 acute toxicities. One patient with a history of naproxen use required suturing with omental patch placement for perforated pyloric ulcer 14 m post-SBRT (18 Gy in single fraction) to the right adrenal metastasis; this region received <5 Gy. Ten patients treated for pain with available follow-up obtained relief. SBRT is a safe and efficacious treatment for adrenal metastases, demonstrating local tumor control. Further study of the impact on survival and quality of life is warranted.

Prostate-Confined Radiation Decreased Pelvic Ganglia Neuronal Survival and Outgrowth

BackgroundErectile dysfunction (ED) is common following radiation therapy (RT) for prostate cancer. Although the cause of RT-induced ED is unknown, damage to both the neuronal and vascular components supporting erections are often implicated. AimTo determine the effects of prostatic RT on erections, penile vascular physiology, and major pelvic ganglia (MPG) neuron growth and survival in a rat model. MethodsMale rats underwent 0 Gy or 22 Gy single fraction of prostate-confined, conformal RT. At 2 weeks or 10 weeks post-RT (n = 10/group), cavernous nerve stimulation was performed and erections were assessed. Tissue bath experiments were performed to assess both penile artery and internal pudendal artery (IPA) function. MPGs were dissociated and neurons grown in culture for 72 hours. Immunofluorescence staining was done to quantify neuron survival (terminal deoxynucleotidyl transferase nick-end labeling), outgrowth (beta-tubulin III), type (nitric oxide synthase [nNOS] and tyrosine hydroxylase [TH]), and nerve injury markers (small GTPase Rac1 and ninjurin-1 [Ninj-1]). Whole MPG real-time quantitative polymerase chain reaction (qPCR) was performed to measure expression of genes related to nerve type, neuron injury, repair, and myelination, such as Ninj-1, Rac1, ATF3, GAP43, GFAP, SOX10, and KROX20. OutcomesIntracavernosal pressure (ICP) to mean arterial pressure (MAP) ratio, smooth muscle contractility and relaxation, gene expression, neuritogenesis, and apoptosis. ResultsFollowing RT, ICP/MAP was unchanged at 2 weeks or 10 weeks. Nerve-mediated penile contraction was increased at 2 weeks, whereas adrenergic contraction was reduced at 10 weeks. Penile relaxation and IPA vasoreactivity were unchanged. Neuronal apoptosis was more than doubled both early and late post-RT. RT caused a progressive decrease in neurite branching but an early increase and then late decrease in neurite lengthening. RT reduced the numbers of nNOS-positive neurons both early and late and also decreased MPG nitrergic gene expression. TH neurons and gene expression were unchanged at 2 weeks; however, both were decreased after 10 weeks. Although most markers of gene injury and repair were unaffected early post-RT, MPG expression of Ninj1 and GFAP increased. After 10 weeks, Ninj1 and GFAP remained elevated while markers of neuron injury (ATF3), outgrowth (GAP43 and Rac1), and myelin regulation (SOX10) were decreased. Clinical TranslationRT-induced ED may result from damage to the ganglia controlling erections. Strengths & LimitationsThis study used a clinically relevant, prostate-confined model to examine neurovascular structures not accessible in human studies. Unfortunately, rats did not exhibit ED at this time point. ConclusionThis is the first study to demonstrate impaired health and regeneration potential of dissociated MPG neurons following RT. Neuronal injury was apparent early post-RT and persisted or increased over time but was insufficient to cause ED at the time points examined.Powers SA, Odom MR, Pak ES, et al. Prostate-Confined Radiation Decreased Pelvic Ganglia Neuronal Survival and Outgrowth. J Sex Med 2019;16:27–41.

32. Linac based VMAT radiosurgery for multiple brain lesions: comparison between a conventional multi-isocenter approach and a new dedicated mono-isocenter 4π technique (HyperArc™)

Purpose Linac based VMAT radiosurgery (SRS) of multiple brain lesions (MBL) is typically performed by a multiple-isocenter approach, i.e.one isocenter per lesion.Here we present the worldwide first experience with a new mono-isocenter technique with multiple non-coplanar arcs (HyperArc, Varian Inc.)in terms of a plan comparison with a multiple-isocenter approach. Methods From August to October 2017, 20 patients with MBL (mean 5, range 2–10) have been treated by HyperArc: prescribed doses ( D p ) were 18–25 Gy in single-fraction, and 21–27 Gy in three-fractions.Total PTV, defined by a 2 mm isotropic margin from each lesion, had mean size of 9.6 cm3 (range 0.5–27.9 cm3).HyperArc VMAT plans (HA), with 5 non-coplanar 180°-arcs (couch at 0°, ±45°, ±90°), and multiple-isocenter VMAT plans (RA), with 2 coplanar 360°-arcs per isocenter, were generated.100% D p at 98%PTV was prescribed, and D 2 % (PTV) D p was accepted.Constraints for 1(3) -fraction to the brainstem, D 0.5cc D 0.5cc V 12 and mean dose to the brain-minus-PTV, MU and overall treatment time (OTT) per fraction.OTT was measured for HA treatments, whereas estimated (3 min.for patient setup plus 5 min.for each CBCT per isocenter) for RA plans. Results As detailed in Table 1 , HA plans resulted in significantly improved CI ( p V 12 to the brain-minus-PTV (p = .023), MU (p D p isodose shells around the targets for the HA plans is depicted for an example patient.By contrast, no significant difference in terms of mean doses to the brain-minus-PTV resulted (p = .31). Conclusions For linac based VMAT-SRS of MBL, HyperArc plans assured a higher CI and a lower GI, a lower V 12 to the brain-minus-PTV, and a lower OTT than standard multiple-isocenter VMAT plans. Finally, all HyperArc treatments were completed within a typical 20 min. time slot.

Short-Course Hyperfractionated Accelerated Radiation Therapy (SC-HART) for Rectal Cancer Stage UICC II – III (8th Edition). Results from a Single Austrian Institution

While short-course radiation therapy (5 x 5 Gy) is a widely tested regimen, Widder et al. introduced a modified regimen with a total dose of 25 Gy given by a single fraction of 2.5 Gy, delivered twice daily [British Journal of Cancer (2005) 92, 1209 – 1214]. Due to the lower single fraction dose compared to the standard regimen, the modified regimen may have better long-term tolerability. The evaluation of the efficacy and the safety of this short course hyperfractionated accelerated radiation therapy (SC-HART) at our institution is presented. We retrospectively evaluated the data of 251 Patients treated with SC-HART from 2002 until 2017. All patients had clinical stage UICC II-III rectal cancer and were treated with 25Gy in 2.5Gy single fractions twice daily. Patients were intended for surgical treatment within 1 week of SC-HART. This report focuses on the patients that received surgery within 1 week of RT. The primary outcomes were locoregional control (LC), freedom from distant metastasis (DM) and overall survival (OS) (Kaplan-Meier) as well as acute toxicities. An analysis of long-term toxicities will be added in a cross-sectional study and presented later. The median age of the patients treated with surgery was 70.7 (37.6-94.1) years. Median follow-up of survivors was 108.7 months. Ninety-eight (39%) patients had stage II, 153 (61%) patients stage III disease. 13 (5.2%) patients experienced a local recurrence, and the median time to local recurrence was 33.1 months. There were no toxicities grade II or higher reported during the SC-HART. The 5-year and 10-year local control, freedom from DM and OS were 95.3%, 94.1%; 89.2%, 87.7% and 71.8%, 57.0%, respectively. SC-HART is an effective and well-tolerated regime in patients with rectal cancer and poses an alternative for the standard fractionated short-course treatment.

Early Outcomes of 19 Gy Single Fraction High Dose Rate Brachytherapy as Monotherapy for Localized Prostate Cancer

Early Outcomes of 19 Gy Single Fraction High Dose Rate Brachytherapy as Monotherapy for Localized Prostate Cancer

LINAC treating more patients having brain arteriovenous malformations with stereotactic radiosurgery technique

Background: Linear accelerator (LINAC) based radiosurgery for a brain arteriovenous malformation (bAVM) is replacing gamma knife radiosurgery. We present clinical outcome, obliteration rates and predictor factors of treatment success following LINAC radiosurgery for bAVM which is not much addressed subject in Middle East. Methods: 13 patients who underwent LINAC radiosurgery for brain arteriovenous malformations from November 2008 to November 2011 in our radiation oncology department were retrospectively analyzed. Recollection of demographic data, AVM and treatment characteristics along with clinical and radiographic follow up information was done by reviewing the electronic data base. Results: All thirteen patients underwent stereotactic radiosurgery by linear accelerator based treatment delivery system (BrainLab) over three years. These included 7 males and 6 females, with median age of 22 years. Intracranial hemorrhage was a presenting feature in 7 (54 %) of patients. Prior embolization was done in 10 (77%) patients with 7 patients having more than once undergone this procedure. The location of AVM was superficial in 9 (70%) and deep in brain in 4 (30%) patients. The mean AVM score was 0.97 with 3 patients having AVM score ≥ 1 with mean Spetzler-Martin grade of 2.7 and 8 (62%) patients having grade 3 or more. Median follow up was 30 months. Mean dose delivered was 21.7 Gy in single fraction. Complete obliteration of AVM nidus was achieved in 9 (70%) patients while 4 patients (30%) had partial obliteration. Six patients (67 %) achieved complete obliteration among 9 who had AVM score of less than 1. Post radiosurgery neurological deficit occurred in only one patient in form of right temporal field loss. Conclusions: Linear accelerator based radiosurgery is promising treatment option for brain AVMs in majority of cases with reasonable adverse effect profile.

5-year Outcomes of a Single Institution Prospective Trial of 19 Gy Single Fraction High Dose Rate Brachytherapy for Low and Intermediate Risk Prostate Cancer

To update the outcome and toxicity results of a prospective trial of 19 Gy single fraction high-dose-rate (HDR) brachytherapy for men with low-intermediate risk prostate cancer.

Gold nanoparticle mediated combined cancer therapy

BackgroundThe combined use of radiation therapy and chemotherapy is commonly being used in cancer treatment. The side effects of the treatment can be further minimized through targeted delivery of anticancer drugs and local enhancement of the radiation dose. Gold nanoparticles (GNPs) can play a significant role in this regard since GNPs can be used as radiation dose enhancers and anticancer drug carriers. Anticancer drug, bleomycin, was chosen as the model drug, since it could be easily conjugated onto GNPs through the gold–thiol bond.MethodsGold nanoparticles of size 10 nm were synthesized using the citrate reduction method. The surface of The GNPs was modified with a peptide sequence (CKKKKKKGGRGDMFG) containing the RGD domain and anticancer drug, bleomycin. Human breast cancer cells (MDA-MB-231) were incubated with 0.3 nM concentration of GNP–drug complex for 16 h prior to irradiation with a 2 Gy single fraction of 6 MV X-rays. After the treatment, cells were trypsinized and seeded in 60 mm dishes for clonogenic assay. Damage to DNA was probed using immunofluorescence assay.ResultsCancer cells internalized with the GNP–drug complex had a 32 ± 9% decrease in cell survival and statistically significant enhancement in DNA (deoxyribonucleic acid) damage as compared to control cells (irradiated with no GNPs) after receiving a radiation dose of 2 Gy with 6 MV photons.ConclusionsThe experimental results demonstrate that GNP-mediated chemoradiation has the potential to improve cancer care in the near future through enhancement of the local radiation dose and controlled delivery of anticancer drugs.

EP-1657: A Study of re-radiation rate after 8 gy single fraction radiotherapy to symptomatic bone metastases

EP-1657: A Study of re-radiation rate after 8 gy single fraction radiotherapy to symptomatic bone metastases

Clinical outcome after high-precision radiotherapy for skull base meningiomas: Pooled data from three large German centers for radiation oncology

PurposeTo evaluate outcome in patients with base of skull meningiomas treated with modern high precision radiation therapy (RT) techniques. Patients and methods927 patients from three centers were treated with either radiosurgery or fractionated high-precision RT for meningiomas. Treatment planning was based on CT and MRI following institutional guidelines. For radiosurgery, a median dose of 13 Gy was applied, for fractionated treatments, a median dose of 54 Gy in 1.8 Gy single fractions was prescribed. Follow-up included a clinical examination as well as contrast-enhanced imaging. All patients were followed up prospectively after radiotherapy in the three departments within a strict follow-up regimen. The median follow-up time was 81 months (range 1–348 months). ResultsMedian local control was 79 months (range 1–348 months). Local control (LC) was 98% at 1 year, 94% at 3 years, 92% at 5 years and 86% at 10 years. There was no difference between radiosurgery and fractionated RT. We analyzed the influence of higher doses on LC and could show that dose did not impact LC. Moreover, there was no difference between 54 Gy and 57.6 Gy in the fractionated group. Side effects were below 5% in both groups without any severe treatment-related complications. DiscussionBased on the pooled data analysis this manuscript provides a large series of meningiomas of the skull base treated with modern high precision RT demonstrating excellent local control and low rates of side effects. Such data support the recommendation of RT for skull base meningiomas in the interdisciplinary tumor board discussions. The strong role of RT must influence treatment recommendations keeping in mind the individual risk–benefit profile of treatment alternatives.

(ICORG 05-03): prospective randomized non-inferiority phase III trial comparing two radiation schedules in malignant spinal cord compression (not proceeding with surgical decompression); the quality of life analysis

Background: The optimal primary external beam radiation therapy (EBRT) radiation schedule for malignant epidural spinal cord compression (MSCC) remains to be determined. The ICORG 05-03 trial assessed if a 10 Gy single fraction radiation schedule was not inferior to one with 20 Gray (Gy) in five daily fractions, in terms of functional motor outcome, for the treatment of MSCC in patients not proceeding with surgical decompression. This article reports on two of the secondary endpoints, Quality of life (QoL), assessed according to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) version 3.0 (EORTC Data Center, Brussels, Belgium) and pain control assessed using a visual analog scale.Methods: A randomized, parallel group, multicenter phase III trial was conducted by Cancer Trials Ireland (formerly All-Ireland Cooperative Oncology Research Group, ICORG), across five hospital sites in Ireland and Northern Ireland. Patients were randomized to 10 Gy single fraction of EBRT or 20 Gy in five fractions in a 1:1 ratio. Patients with baseline and 5-week follow up QoL data are included in this analysis.Findings: From 2006 to 2014, 112 eligible patients were enrolled for whom 57 were evaluated for this secondary analysis. After adjusting for pre-intervention scores, there was no statistically significant difference in post-treatment Summary scores (excl. FI and QL), or pain scores between the two RT schedules at 5 weeks and 3 months following EBRT. There was a statistically significant relationship between the pretreatment and post-treatment Summary scores (p = .002) but not between the pre-treatment and post-treatment pain scores.Interpretation: Primary radiotherapy for the treatment of MSCC significantly improves QoL in patients not proceeding with surgical decompression. After adjusting for pre-intervention scores, there was no statistically significant difference between a 10 Gy single fraction radiation schedule and one with 20 Gy in five daily fractions on post-treatment QoL Summary scores. For most patients, an effective treatment with low burden would be desirable. A single fraction schedule should be considered for this group of patients.

Efficacy of 8 Gy Single Fraction Palliative Radiation Therapy in Painful Bone Metastases: A Single Institution Experience.

IntroductionBone metastasis (BM) is a major complication of many solid tumors like breast, prostate, lung and renal cancers. BM leads to serious sequelae of pain, fractures, spinal cord compression and hypercalcemia. Radiotherapy has an established role in relieving pain caused by BM. Worldwide different radiotherapy schedules are being used for BM. The aim of this study is to determine the efficacy of single fraction palliative radiotherapy for painful bone metastases.MethodsBetween April 2014 and April 2017, single fraction radiotherapy was used to treat 73 patients in our institution. They had pathologically proven breast, prostate, lung or renal cancer with radiological evidence of bone metastases. There were 39 males (53%) and 34 females (47%). The median age was 58 years (range 33–87 years). 39% patients (n = 28) had breast cancer, 35% had prostate cancer (n = 26), 23% had lung cancer (n = 17), and 3% had renal cancer (n = 2). On presentation, all the patients had a pain score of more than five on Brief Pain Inventory (BPI).ResultsResponse assessment to pain after three months from single fraction radiotherapy was found to be complete response (CR) in 23% patients (n = 17), partial response (PR) in 38% patients (n = 28), stable disease (SD) in 26% patients (n = 19) and progressive disease (PD) in 12% patients (n = 9). The overall efficacy of treatment was 62%, with CR 23% and PR 38%. Pre-treatment mean pain score was 8.15 compared to 4.68 post-treatment (p < 0.001).ConclusionsSingle fraction palliative radiotherapy of 8 Gy showed significant efficacy in painful bone metastases in our setting and merits further investigation in our population.

Single fraction computed tomography-guided high-dose-rate brachytherapy or stereotactic body radiotherapy for primary and metastatic lung tumors?

PurposeTo provide a pilot dosimetric study of computed tomography (CT)-guided high-dose-rate (HDR) brachytherapy (BRT) and stereotactic body radiotherapy (SBRT) for primary and metastatic lung lesions.Material and methodsFor nine lung primary and metastasis patients, 3D image-based BRT plan using a single virtual catheter was planned for 34 Gy in single fraction to the gross tumor volume (GTV) + 3 mm margin to account for tumor deformation. These plans were compared to margin-based (MB-) and robustness optimized (RO-) SBRT, assuming the same tumor deformation under real-time tumor tracking. Consistent dose calculation was ensured for both BRT and SBRT plans using the same class of collapsed cone convolution superposition algorithm. Plan quality metrics were compared by Friedman tests and Wilcoxon t-tests.Results and ConclusionsBrachytherapy plans showed significant higher GTV mean dose compared to MB- and RO-SBRT (122.2 Gy vs. 50.4 and 44.7 Gy, p < 0.05), and better dose gradient index (R50) = 2.9 vs. 4.3 and 8.4 for MB- and RO-SBRT, respectively. Dose constraints per the RTOG 0915 protocol were achieved for all critical organs except chest wall in BRT. All other dose-volume histograms (DVH) metrics are comparable between BRT and SBRT. Treatment delivery time of BRT and SBRT plans significantly increased and decreased with increasing GTV size, respectively. SBRT using advanced MLC tracking technique and non-coplanar VMAT can achieve comparable dosimetric quality to HDR BRT. Whether or not, the significantly higher GTV dose can increase killing of radioresistant tumor cells and offset the effect of tumor reoxygenation in single fraction BRT, requires further clinical investigation.

Single-fraction radiation: A promising adjuvant therapy to prevent keloid recurrence.

Keloids are characterized by collection of atypical fibroblasts with excessive deposition of extracellular matrix components. Keloids are prone to high recurrence (50%-80%) with unimodality treatment. Radiation is a promising approach among the adjuvant modalities in vogue though consensus is lacking on dose-fractionation schedule. The present study aimed to analyze the efficacy of single-fraction high-dose adjuvant radiotherapy to prevent keloid recurrence. Details of patients treated for keloids using external beam radiation therapy from January 2011 to December 2016 were retrieved from electronic medical records and radiation therapy charts and analyzed. Thirty-seven keloid lesions in thirty patients were analyzed. Keloids received radiation within 24-72 h postsurgery using 6 MeV electron beam. 45.9% of keloids were in the chest wall. Dose ranged between 5 Gy and 12 Gy in 1-3 fractions. Eight Gy was used in 78.4%. The single fraction was preferred in 91.9%. Good cosmesis was achieved in all except three who had wound dehiscence. Median follow-up was 32.67 months. 16.2% had recurrence. Median time to recur was 13.6 months, and median recurrence-free interval 21.23 months. Among those who received 8 Gy single fraction, 73.4% remained recurrence-free at 5 years. Albeit a retrospective analysis, ours is the only study in literature offering 8 Gy single dose, using electrons, as a postoperative adjuvant treatment to prevent recurrence in keloids. Our recurrence rates were similar to that quoted in published series. This hence can be validated in further studies as it is cosmetically acceptable, safe, painless, and cost-effective with good patient compliance.

Comparison of Single Versus Multifraction Radiotherapy in Palliation of Painful Bone Metastases.

BackgroundBone is a common site of dissemination in advanced cancer accounting for one-third of all distant metastases. Various fractionation schedules of radiotherapy have been used for palliation of bone metastases. The aim of this study was to compare three schedules of external radiation therapy (8 Gy single session versus 20 Gy/5 fractions versus 30 Gy/10 fractions) for palliative management of bone metastases.MethodsIn the present study, 60 patients of bone metastases from any primary site were enrolled and randomly divided into three groups of 20 patients each by draw of lots. These patients received palliative external beam radiation therapy to the involved site. Patients were given 8 Gy single session, 20 Gy/5 fractions/1 week and 30 Gy/10 fractions/2 weeks in groups I, II and III, respectively.ResultsThe percentage of patients with overall pain relief was 80% in group I, 75% in group II and 85% in group III (P = 0.7). The number of patients with complete pain relief was 4 (20%) in each group. Maximum patients got pain relief at 4 weeks post-radiotherapy. The number of patients with improved performance status was 4 (20%) in group II and 2 (10%) each in groups I and III (P = 0.5). Thirteen (65%) patients in each of the groups had decreased analgesic requirement at 2-month follow-up. Retreatment rate was more in the single fraction (20%) compared to only 5% in group II and none in the group III (P = 0.05).ConclusionFrom the present study we conclude that 8 Gy single fraction is as effective as multifraction radiotherapy for the palliation of painful bone metastases. However, for a center like ours being the only Government Tertiary Cancer Care Centre in the State, general consensus drawn after this study, recommends external radiation therapy 20 Gy/5 fraction regimen to be an appropriate means of palliation of painful bone metastases.

Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial

Whole brain radiotherapy (WBRT) is the standard of care to improve intracranial control following resection of brain metastasis. However, stereotactic radiosurgery (SRS) to the surgical cavity is widely used in an attempt to reduce cognitive toxicity, despite the absence of high-level comparative data substantiating efficacy in the postoperative setting. We aimed to establish the effect of SRS on survival and cognitive outcomes compared with WBRT in patients with resected brain metastasis. In this randomised, controlled, phase 3 trial, adult patients (aged 18 years or older) from 48 institutions in the USA and Canada with one resected brain metastasis and a resection cavity less than 5·0 cm in maximal extent were randomly assigned (1:1) to either postoperative SRS (12-20 Gy single fraction with dose determined by surgical cavity volume) or WBRT (30 Gy in ten daily fractions or 37·5 Gy in 15 daily fractions of 2·5 Gy; fractionation schedule predetermined for all patients at treating centre). We randomised patients using a dynamic allocation strategy with stratification factors of age, duration of extracranial disease control, number of brain metastases, histology, maximal resection cavity diameter, and treatment centre. Patients and investigators were not masked to treatment allocation. The co-primary endpoints were cognitive-deterioration-free survival and overall survival, and analyses were done by intention to treat. We report the final analysis. This trial is registered with ClinicalTrials.gov, number NCT01372774. Between Nov 10, 2011, and Nov 16, 2015, 194 patients were enrolled and randomly assigned to SRS (98 patients) or WBRT (96 patients). Median follow-up was 11·1 months (IQR 5·1-18·0). Cognitive-deterioration-free survival was longer in patients assigned to SRS (median 3·7 months [95% CI 3·45-5·06], 93 events) than in patients assigned to WBRT (median 3·0 months [2·86-3·25], 93 events; hazard ratio [HR] 0·47 [95% CI 0·35-0·63]; p<0·0001), and cognitive deterioration at 6 months was less frequent in patients who received SRS than those who received WBRT (28 [52%] of 54 evaluable patients assigned to SRS vs 41 [85%] of 48 evaluable patients assigned to WBRT; difference -33·6% [95% CI -45·3 to -21·8], p<0·00031). Median overall survival was 12·2 months (95% CI 9·7-16·0, 69 deaths) for SRS and 11·6 months (9·9-18·0, 67 deaths) for WBRT (HR 1·07 [95% CI 0·76-1·50]; p=0·70). The most common grade 3 or 4 adverse events reported with a relative frequency greater than 4% were hearing impairment (three [3%] of 93 patients in the SRS group vs eight [9%] of 92 patients in the WBRT group) and cognitive disturbance (three [3%] vs five [5%]). There were no treatment-related deaths. Decline in cognitive function was more frequent with WBRT than with SRS and there was no difference in overall survival between the treatment groups. After resection of a brain metastasis, SRS radiosurgery should be considered one of the standards of care as a less toxic alternative to WBRT for this patient population. National Cancer Institute.