Acute Radiation Toxicity Research Articles

Evaluation of Acute Toxicity and Dosimetric Parameters in High Risk Prostate Cancer Patients Treated by High Radiation Doses

For high risk prostate cancer, the treatment volumes and even dose levels are still a controversial issue. The aim of this study is to evaluate the dosemetric parameters and acute toxicity of dose-escalated whole pelvis (WP) Intensity Modulated Radiation Therapy (IMRT) and volumetric modulated arc therapy (VMAT) prostate boost following neoadjuvant and concomitant with androgen deprivation therapy in high-risk prostate cancer patients. This analysis included 73 high-risk prostate cancer patients treated with WP-IMRT followed by boost to the prostate by VMAT to total dose of 80 Gy; between January 2014 and October 2016. Androgen deprivation therapy (ADT) was given for all patients before and during radiation therapy. Drawing the dose volume histograms (DVHs) was done for planning target volumes (PTVs), including Prostate PTV & nodal PTV, and organs at risk including rectum, bladder, femoral heads, and bowel bag for the plans. Acute radiation toxicities were reported during the radiation course and the following 3 months. The DVH analysis showed good coverage of PTVs and organs at risk doses were acceptable. No recorded acute Grade ≥ 3 toxicity. Acute grade 1 toxicity for Gastrointestinal (GI) and Genitourinary (GU) were 65% and 35% respectively, while Grade 2 toxicity was 30% for both. The Proctitis and frequency were the commonest acute toxicity and were maximal during the 5th week of radiation therapy. Dose escalation in two phases utilizing Simultaneous integrated boost (SIB) combined with ADT in high risk prostate cancer patient is feasible and associated with acceptable acute GI and GU toxicity.

Akutni radiodermatitis tokom zračne terapije

Acute radiation skin toxicity is the most common of all radiation toxicities during radiotherapy. More than 90% of the patients receiving radiotherapy have some form of radiodermatitis. There are many risk factors for radiodermatitis. The most important symptom is pain. Modern treatment technics, such as intensity modulated radiotherapy (IMRT) are giving for decreased severity and incidence of radiodermatitis. In treatment of acute skin radiation toxicity are necessary pain management and adequate skin care.

A comparison of six fractions per week chemoradiation versus five fractions per week of conventional chemoradiation in carcinoma cervix: A prospective controlled study.

The standard of care for carcinoma cervix stage IB2-IVA is five fractions per week of radiotherapy (RT) with concurrent cisplatin. We compared the standard treatment with six fractions per week of RT with concurrent Cisplatin to see whether the later had improved survival outcomes with comparable toxicities. 46 patients of carcinoma cervix with stage IB2-IVAwere randomized into two arms. Study arm: 46 Gy/23 fractions/26 days, 6 fractions/week with injection CDDP 40 mg/m2 and Control arm: 46 Gy/23 fractions/31 days, 5 fractions/week with injection Cisplatin 40mg/m2. Patients in both the arms received LDR brachytherapy to a dose of 29 Gy at point A. The primary end points were disease-free survival (DFS) and overall survival (OS). Compliance to treatment and treatment toxicities were the secondary end points. P value ≤0.05 were considered significant. The study was carried out during June, 2014-April, 2015. Statistical analysis was done in May, 2019. Of 46 patients, 39 patients completed the treatment. The study and control arms had 17 and 22 patients, respectively. Median follow-up period is 45 months (range: 1-54 months). 3-year DFS rates and OS was 69.5% vs. 72.7% (P = 0.73) and 63% vs. 68% (P = 0.45) in study and in control arm, respectively. There was no significant difference in acute and late radiation toxicities between two arms. Chemoradiotherapy with six fractions per week seems feasible and equally efficacious in terms of survival outcomes and toxicity profile. Further prospective randomized controlled study is required to prove the merit of altered fractionation with concurrent cisplatin.

DNA Damage and Immune Response Biomarkers May Predict Toxicity and Response to Radiation Therapy Using a Blood Based Test

Radiation therapy is a critical part of cancer patient treatment regimens. While many patients respond to radiation therapy, others will not respond or will have toxicities that significantly reduce quality of life or outcome. Our objective was to create a gene expression assay from peripheral blood to predict radiation toxicity and/or response, thus allowing doctors to modify therapy based on the patient’s genetic background. A 302 gene Ampliseq RNA sequencing panel was developed to study radiation toxicity and response by performing Whole Genome Correlation Network Analysis (WGCNA) of publicly available radiation toxicity gene expression data sets in tissue, and radiation response (total body irradiation radiation biodosimetry data sets) in blood. To identify biological pathways of significance in therapy responders, KEGG and DAVID Analysis of the gene panel was performed on microarray data from the tissue of 71 prostate cancer and 318 glioblastoma patients in The Cancer Genome Atlas (TCGA). A targeted 31 gene assay was developed on a proprietary genomics platform. and a prospective study of 81 pelvic cancer patients representing 17 different cancer types was performed. This cohort included 34 patients reporting Grade 2 or Grade 3 acute radiation toxicity (3-month follow-up), and 12 rectal cancer patients with known tumor response. KEGG and DAVID analysis of the 302-gene radiation panel revealed a predominance of genes related to DNA repair, P53 signaling, Cell Cycle, Protein Ubiquitination, and Immune Response. In-silico analysis of the TCGA data revealed clear separation of responders and non-responders in the 71-patient prostate cancer data set, and clustering by survival after treatment in the 318-patient glioblastoma data set. Testing of pre-irradiation blood samples in the 81-patient prospective pelvic cancer study with the 31-gene assay showed 80.6% sensitivity and 90.7% specificity for predicting stage 2 or higher acute radiation toxicity, and 83.3% sensitivity and 85.7% specificity for predicting rectal cancer tumor response in the 12 rectal cancer patients with known Tumor Response Grading (TRG 0-4). A second IRB approved study is currently accruing additional patients to further validate these results. We were able to develop a gene expression signature from peripheral blood samples of cancer patients to predict radiation toxicity and response prior to the initiation of therapy. The blood based gene signature, comprised primarily of DNA damage and immune response genes, identified several genes also identified as biomarkers of radiation response/radiosensitivity from rectal cancer tumor samples. These results indicate that a gene expression based blood test may be developed to assist in radiation treatment decisions.

Monte-Carlo Based Total-Body Irradiation Using Linac-Based Volumetric Modulated Arc Therapy

To assess the accuracy, feasibility, and reliability of a total-body irradiation (TBI) technique with linac-based volumetric modulated arc therapy (VMAT) in patients with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). From 2015-2017, 26 patients (15 men, 11 women) with AML or ALL underwent allogenic stem-cell transplantation following TBI with linac-based VMAT technique, which consisted of three isocenters and three overlapping arcs for head first CT sets. We added one or two more overlapping arcs, depending on the height of the patient for feet first CT sets. Patient age ranged from 6-63 years with a mean and median age of 20.5 and 17.5 years, respectively. TBI dose was prescribed to 90% of the clinical target volume receiving 12 Gy in six fractions, at two fractions per day. Mean lung and kidney doses were restricted less than 10 Gy, and maximum lens dose less than 6 Gy. Dose rate was variable, and mean dose rate was 250 MU/min. Calculation parameters were grid spacing 0.4 cm, minimum segment width 0.5 cm, maximum 180 control points per arc, fluence-smoothing medium, statistical uncertainty 1.0% per calculation, gantry increment of 30°, and calculate dose deposition to medium. Patients were immobilized in supine position using customized thermoplastic masks for head support and a vacuum cushion for body support on an adjustable combined immobilization board. Laser-based optical surface-guided devices were used for patient positioning and intra-fraction motion detection. Quality assurance (QA) comprised the verification of the radiation plans via dose-volume histograms (DVH) based 3D patient QA system. Average mean lung dose was 9.7 ± 0.2 Gy, mean kidney dose 9.6 ± 0.2 Gy, maximum lens dose 4.5 ± 0.4 Gy, mean planning treatment volume (PTV) dose 12.7 ± 0.1 Gy, and heterogenity index of PTV was 1.16 ± 0.02 in all patients. Overall acute toxicity was low with only grade 1 and 2 morbidity: patchy mucositis in 16 (62%), nausea not requiring antiemetics in 12 (46%), headache in 11 (42%), fatigue in 9 (35%), neck pain in 8 (31%), xerostomia in 7 (27%), loss of appetite in 6 (23%), and faint or dull erythema in 4 (15%) patients. Grade 3 and more acute radiation toxicity was not observed. All patients are stil alive. When comparing plan and DVH-based 3D patient QA results, average differences of 3.4% ± 1.3 in mean kidney doses, 1.0% ± 0.7 in mean lung doses, and 0.9% ± 0.4 in mean target doses were observed. Linac-based VMAT simplifies the process of TBI, and is accurate, feasible, and reliable. Partial cone-beam CT and optical surface-guided system assure patient positioning. Moreover, up to 6-mm longitudinal misalignment does not cause an average more than 3.5% mean lung dose enhancement. DVH-based 3D patient dose verification QA was possible with linac-based VMAT showing small differences between planned and delivered doses.

Initial Clinical Experience with Uni-Directional LDR Brachytherapy in the Treatment of Retroperitoneal Sarcoma

Retroperitoneal sarcomas (RPS)s constitute 10%-15% of patients diagnosed with soft tissue sarcomas. Despite advances in cancer care and aggressive management, the 5-year overall survival rate is 47%-67%. The crude cumulative incidence of local recurrence (LR) is 26%. A previous trial combining preoperative external beam radiation therapy with post-operative brachytherapy found substantial toxicity and treatment related death. This report demonstrates the utility of unidirectional LDR brachytherapy for treatment of RPS. In this study, the unidirectional device employed is a permanent, Pd-103 brachytherapy device designed to be implanted during surgical resection for the treatment of anticipated positive or close surgical margins. The device consists of a plane of sources with an unidirectional gold shield backing to protect normal tissues yet direct radiation to the target margin(s). The sources are embedded in a bio-absorbable matrix membrane that may be cut to size to allow for conformal targeting of the surgical tumor bed. At surgery, patients were assessed and determined to have close or positive margins. The prescribed LDR brachytherapy dose averaged 34.7 Gy (range: 20 – 60 Gy) and covered an average area of 6060 mm2 (∼58 sources). Pd-103 has a half-life of 16.99 days and delivers therapeutic radiation dose over several weeks. The device was attached with sutures and tacks. Seven RPS patients have been implanted with the CivaSheet at 4 medical centers. Six patients had recurrent sarcoma in the retroperitoneum or pelvic side wall. One patient had locally advanced leiomyosarcoma with no previous treatment. Three patients had prior EBRT at first diagnosis (45 – 57.5 Gy). Five patients received neoadjuvant EBRT (35 – 57.5 Gy) prior to surgery plus brachytherapy. The patients tolerated the implant well with no complications following surgery. There have been 0 reports of source movement in RPS patients. At median 15 months (8-24 months) follow-up, 0/7 patients have demonstrated local recurrence as defined as the targeted field of brachytherapy radiation. One patient (1/7) recurred outside of the surgical field and subsequent brachytherapy radiation. There were 0 reported incidences of acute or late radiation toxicity despite the surrounding organs at risk, inclusive of the small intestine, ureter and kidneys. Unidirectional, planar Pd-103 LDR brachytherapy has demonstrated a 100% local recurrence free survival with no acute or late-term toxicities at a median of 15 months in our patient cohort. Application of uni-directional, planar Pd-103 LDR brachytherapy technology is very safe and easy, and should be considered to escalate dose or retreat to the high risk margins of RPS after resection.

Total-body irradiation using linac-based volumetric modulated arc therapy: Its clinical accuracy, feasibility and reliability

PurposeTo report the feasibility, accuracy, and reliability of volumetric modulated arc therapy (VMAT)-based total-body irradiation (TBI) treatment in patients with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). Materials and methodsFrom 2015 to 2018, 30 patients with AML or ALL were planned and treated with VMAT-based TBI, which consisted of three isocenters and three overlapping arcs. TBI dose was prescribed to 90% of the planning treatment volume (PTV) receiving 12 Gy in six fractions, at two fractions per day. Mean lung and kidney doses were restricted less than 10 Gy, and maximum lens dose less than 6 Gy. Quality assurance (QA) comprised the verification of the irradiation plans via dose–volume histogram (DVH) based 3D patient QA system. ResultsAverage mean lung dose was 9.7 ± 0.2 Gy, mean kidney dose 9.6 ± 0.2 Gy, maximum lens dose 4.5 ± 0.4 Gy, mean PTV dose 12.7 ± 0.1 Gy, and heterogeneity index of PTV was 1.16 ± 0.02 in all patients. Grade 3 or more acute radiation toxicity was not observed. When comparing plan and DVH-based 3D patient QA results, average differences of 3.3% ± 1.3 in mean kidney doses, 1.1% ± 0.7 in mean lung doses, and 0.9% ± 0.4 in mean target doses were observed. ConclusionLinac-based VMAT increased the dose homogeneity of TBI treatment more than extended SSD techniques. Partial cone-beam CT and optical surface-guided system assure patient positioning. DVH-based 3D patient dose verification QA was possible with linac-based VMAT showing small differences between planned and delivered doses. It is feasible, accurate, and reliable.

Acute radiotherapy toxicity in 57 dogs with gross and microscopic mast cell tumours.

Mast cell tumours (MCTs) are commonly treated with radiation therapy, most often in a microscopic disease setting. Poorer outcomes are expected in patients with gross disease, and irradiation of gross disease may be associated with greater toxicity. The aim of this study was to compare acute radiation adverse events (AE) in dogs with gross and microscopic MCTs receiving radiotherapy. Fifty-seven dogs were included, 28 with gross disease and 29 with microscopic. In order to assess mucosal and skin toxicity, patients were assigned to 2 groups: head (29 patients, 14 patients with gross and 15 microscopic) and other sites (28 patients, 14 each). All were treated with external beam radiotherapy, and toxicity assessed at the end of treatment and 10 to 14 days later (first recheck). All patients developed some acute radiation toxicity by the end of the course. However, there was no difference in the severity of toxicity between gross and microscopic disease in either site group at either time point. The only variable associated with an increased frequency of grade 2 or 3 toxicity at the first recheck was the use of prednisolone prior to radiotherapy (P = .05). No other factors were identified which were associated with increased toxicity. For the head group, the site of highest grade toxicity was mucosa or, if included in the field, nasal planum, which was often more severely affected than the mucosa. No significant late toxicity was identified. Two dogs developed acute haematemesis during the radiotherapy course, but both completed the course without further events.

Acute Epithelial Toxicity Is Prognostic for Improved Prostate Cancer Response to Radiation Therapy: A Retrospective, Multicenter, Cohort Study

Totest the hypothesis that increased acute toxicity, measured using subdomains reflective of epithelial cell damage, will be associated with reduced late biochemical failure, as a surrogate for tumor radiosensitivity. The study design was retrospective, with discovery and validation cohorts involving routinely collected data. Eligible patients had prostate cancer, underwent radiation therapy with curative intent, and had acute toxicity assessed prospectively. The discovery cohort was from a single institution. Genitourinary and gastrointestinal acute toxicity related to epithelial cell damage (hematuria, dysuria, proctitis, or mucus) were related to freedom from late biochemical failure (FFBF; nadir+2). The validation cohort was from two separate institutions. In all, 503 patients were included in the discovery cohort and 658 patients in the validation cohort. In the validation cohort, patients with acute radiation toxicity reflecting epithelial damage had a longer FFBF on both univariate (hazard ratio [HR] 0.37; P=.004) and multivariate (HR 0.45; P=.035) analysis. The impact of acute toxicity on late FFBF seemed to be greater in patients treated with androgen deprivation (HR 0.19) than in those without (HR 0.48). Patients reporting acute radiation toxicity reflective of epithelial cell damage during definitive radiation therapy for prostate cancer have significantly longer FFBF, consistent with an underlying genetic link between normal tissue and tumor radiosensitivity.

Comparison of Locoregional Control, Acute Radiation Toxicities and Patient Compliance between Two Different Radiation Fractionation Schedules with Concurrent Chemotherapy in Oropharyngeal Cancer

Comparison of Locoregional Control, Acute Radiation Toxicities and Patient Compliance between Two Different Radiation Fractionation Schedules with Concurrent Chemotherapy in Oropharyngeal Cancer

SBRT of Recurrent HNC Should be Most Effective in Patients With Nasopharyngeal or Small Volume Lesions

Precise beam-delivery techniques like SRT/SBRT have allowed reirradiation as a potentially curative salvage therapy. It is generally agreed that SBRT remains a reasonable choice of salvage for inoperable recurrence of head and neck cancer, because its GTV-limited dose delivery prevents acute radiation toxicity and offers acceptable treatment tolerance. This is a retrospective analysis of reirradiation of 65 patients with recurrent HNC using microbeam SBRT over 2010-2017. The median age of the patients was 58 years (range, 28–91 years), with 38 males and 27 females. All recurrences occurred in the previously radiated with the dose ≥40 Gy. Patients who received SBRT as a planned boost after primary radiation therapy and those who had second primary tumor outside the reirradiation area were excluded from the analysis. Recurrent HNC characteristics were as follows: according to primary site—24 NPC, 17OPC, 15 OCC, 4 HPC, 3 with nasal cavity, and 2 with LXC; according to T stage—9 T0, 10rT1, 26rT2, 13rT3, and 7rT4; according to N stage—52 rN0, 9rN1, and 4 N2. Patients had received median dose in PTV of 24 Gy (minimum 5 Gy, maximum 52 Gy, mean: 22, 7 Gy ± 8.65 Gy SD in 1-13 fractions). The median BED (for alpha/beta = 3 Gy) from first radiation was 60.48 Gy (range 46.8-72 Gy), from secondary radiation was 66.7 Gy (range 13.3-121 Gy) and sum of both treatments was 127 Gy (range 62-156 Gy). The median follow-up time for all reradiated patients was 16 months, and the 2-year overall survival rate was 27%. Estimated prognostic factors for overall survival were: primary site (nasopharynx versus other sites), PTV maximal diameter, and PTV volume. Detailed analysis of PTV maximal diameter and PTV volume showed a lower response rate in patients with tumor diameter greater than 4cm (65%) and volume greater than 21cm3 (34%), compare to <4cm (80%; P=.045) and <21cm3 group (53%; P=.008). The 2-year overall survival rates were 16.4% in the >4cm PTV maximal diameter group and 34% (P=.003) in the <4cm PTV maximal diameter group and 22% in the >21cm3 PTV volume group and 32.5% (P=.002) in the <21cm3 PTV volume group. We recorded 2 incidents of haemorrhage during reirradiation in the >4cm PTV maximal diameter group. For recurrent HNC patients, the “r” tumor site, the amount of PTV volume, and PTV maximal diameter are significant prognostic factors for patient survival after reirradiation using SBRT.

Akutna radijaciona toksičnost za vreme i posle hemoradioterapije kod pacijentkinja sa lokalno uznapredovalim karcinomom cerviksa uterusa

Akutna radijaciona toksičnost za vreme i posle hemoradioterapije kod pacijentkinja sa lokalno uznapredovalim karcinomom cerviksa uterusa

Prediction of acute gastrointestinal and genitourinary radiation toxicity in prostate cancer patients using lymphocyte microRNA.

To search for novel biomarkers that can predict acute radiation toxicity, we conducted microRNA expression analysis of peripheral blood lymphocytes (PBLs). The discovery cohort was 69 patients with localized adenocarcinoma of the prostate who received intensity-modulated radiation therapy between October 2007 and October 2010. The validation cohort was 72 patients treated with low-dose-rate brachytherapy between May 2008 and March 2014. After13 microRNAs were selected by TaqMan® Array analysis in a preliminary experiment, expression of these microRNAs in all samples was analyzed by RT-PCR. In the discovery cohort, the average prostate volume, the rectal volume receiving 70 Gy, and expression of miR-410 and miR-221 were significant risk factors for Grade 1-2 gastrointestinal toxicity. Receiver operating characteristic analysis showed that the area under the curve (AUC) was 0.807. The maximum dose to the urinary bladder, prostate volume, pretreatment urinary function score, and miR-99a and miR-221 expression were risk factors for Grade 2 genitourinary toxicity. The corresponding AUC was 0.796. In the validation cohort, reproducibility of these markers was confirmed for gastrointestinal toxicity, but not for genitourinary toxicity. Combining radiation dose parameters with microRNA expression in PBLs may be useful for predicting acute gastrointestinal toxicity of radiation therapy, thus contributing to personalized treatment of prostate cancer.

A Phase 2 Study of 2 Weeks of Adjuvant Whole Breast/Chest Wall and/or Regional Nodal Radiation Therapy for Patients With Breast Cancer

To report the results in terms of feasibility and early toxicity of hypofractionated adjuvant whole breast/chest wall and/or regional nodal radiation therapy for patients with breast cancer. From June 2013 to October 2014, 50 patients with breast cancer after mastectomy or after breast conservation surgery (BCS) were prospectively included. The institutional ethics committee approved the study, which was registered with ClinicalTrials.gov (ClinicalTrials.gov identifier no. NCT02460744). Treatment planning was performed using a simulator with 2 tangential fields to the breast/chest wall and an incident field to the supraclavicular fossa. The radiation dose delivered was 34Gy in 10 fractions within 2weeks, followed by a boost of 10Gy in 5 fractions within 1week for patients who underwent BCS. Acute skin toxicities were recorded during and after treatment according to the Radiation Therapy Oncology Group acute radiation toxicity scoring criteria. The primary objective was to obtain estimates of the acute toxicity rates and cosmetic outcomes that could be used to design a subsequent phase III comparative study. Acute skin and late toxicities were recorded during and after treatment. Cosmetic outcomes were assessed before and after treatment and during the regular follow-up period. A cost/benefit analysis was also performed and compared with that for standard treatment of 35Gy in 15 fractions within 3weeks. The median follow-up was 39months (range 14-48). The mean age was 51years (range 26-75). A left-sided tumor was present in 25 patients (50%). Total mastectomy with axillary clearance was performed in 40 (80%) and BCS in 10 (20%) patients. Acute grade 2 and 3 skin toxicity was seen in 16 (32%) and 1 (2%) patient, respectively. In the BCS patients, grade 2 skin and subcutaneous toxicity was seen in 2 (20%) and 1 (10%) patient, respectively. Grade 2 edema was seen in 1 patient (10%). The cosmesis was excellent or good in 8 (80%) and fair or poor in 2 (20%) patients. The cost/benefit analysis revealed significantly less financial burden on the patients with 2weeks of treatment. Disease-free and overall survival at 3years was 94% and 96%, respectively. Hypofractionated radiation therapy within 2weeks appears to be feasible for patients with breast cancer and was associated with acute and late skin toxicity profiles similar to those observed with 3weeks of treatment. The financial burden on the patient and family could be reduced with 2weeks of treatment. Long-term follow-up data and a prospective comparative study are needed to strengthen these results. Hypofractionation might help radiation centers worldwide to meet the increasing need for radiation for breast cancer, especially in developing countries where resources are limited and patients must travel long distances for treatment.

Effects of radiotherapy on oral cavity tissues

Abstract Radiotherapy in the treatment of head and neck tumors is most often used as an independent method or in combination with surgery and / or chemotherapy. These therapeutic methods in a multidisciplinary approach generally lead to favourable therapeutic response. During radiotherapy of this region, oral mucosa is inevitably covered within irradiated volume. Radical therapy is achieved with high doses of radiation, which usually results in development of undesired toxic effects, which, depending on the time of manifestation can be acute and late. Acute radiation toxicity occurs during or immediately after completion of performed therapy, and the late one several months or years after the completed treatment. The most common acute complications in the oral cavity are inflammation of oral mucosa, loss of taste, dry mouth and secondary infections. Late complications include radiation caries, trismus, and osteoradionecrosis. The aim of this paper was to present the effects and specificities of toxicity observed on oral cavity tissues after radiotherapy.

Pelvic bone anatomy vs implanted gold seed marker registration for image-guided intensity modulated radiotherapy for prostate carcinoma: Comparative analysis of inter-fraction motion and toxicities

ObjectivesWe compared the prostate motion variability and toxicities between patients treated with gold marker registration based IG-IMRT (IG-IMRT-M) and bony landmark registration based IG-IMRT (IG-IMRT-B). MethodsT1c-T3b (node negative), intermediate and high risk (non-metastatic) adenocarcinoma of prostate, age ≥18years, Karnofsky Performance Status of ≥70 were included in this retrospective study. The prostate motion variability, acute and late radiation toxicities between the two treatment arms (IG-IMRT-M versus IG-IMRT-B) were compared. ResultsTotal of 35 patients (17 for IG-IMRT-M and 18 for IG-IMRT-B) were treated with a median radiotherapy dose of 76 Gray. The prostate variability observed with and without markers in millimeter was 4.1±2.3 vs 3.7±2.1 [Antero-Posterior (A-P); p=0.001], 2.3±1.5 vs 2.1±1.2 [Superior-Inferior (S-I); p=0.095] and 1.1±1.7 vs 0.4±1.4 [Left-Right (L-R); p=0.003]. There was higher acute toxicity in IG-IMRT-B arm compared to IG-IMRT-M arm in terms of grade ≥2 diarrhea [50% vs 11% OR=7.5 (1.3–42.7); p=0.02] and grade ≥2 proctitis [38% vs 5.8%, OR=10.1 (1.09–94.1); p=0.04]. At a median follow up of 36months, the late genitourinary toxicities grade ≥2 [27% vs 0%; p=0.04] were higher in the IG-IMRT-B arm compared to IG-IMRT-M arm. ConclusionsIG-IMRT-M detects higher prostate motion variability as compared to IG-IMRT-B, inferring a significant prostate motion inside fixed pelvic bony cavity. The addition of marker based image guidance results in higher precision of prostate localization and lesser acute and late toxicities.

Postmastectomy intensity modulation radiated therapy of chest wall and regional nodes: Retrospective analysis of the performance and complications up for 5 years.

To retrospectively evaluate the performance and complications of postmastectomy intensity modulation radiated therapy (IMRT) technique.From January 2010 to December 2014, IMRT technique was applied to 200 patients after modified radical mastectomy. The acute and late radiation toxicities have been followed up for 5 years. The treatment performance, toxicity incidence, and risk factors were investigated.All patients included had at least 1-year of follow-up; mean follow-up was 28.5 months. Three patients had grade 3 acute radiation dermatitis; 1 patient received grade 2 acute radiation induced lung injury, while 3 patients received acute radiation esophagitis. Seven patients had edema at the end of radiotherapy. Multivariate analyses revealed that neoadjuvant chemotherapy and hypertension were the most significant risk factors for acute skin dermatitis and acute radiation induced lung injury, respectively. Trastuzumab treatment was the independent risk factor for late radiation lung injury. Internal mammary nodes irradiation might relate to acute and late radiation induced lung injury. In the follow-ups there were 125 patients that were followed up with for >2 years. The 2-year local-regional recurrence (LRR), distant metastasis (DM), and disease free survival (DFS) were 1.6%, 6.4%, and 92.80%, respectively.Postmastectomy treatment with the IMRT technique can reduce the incidence rate of radiation toxicity by decreasing organs at risk (OARs) irradiation. Patients with risk factors for radiation toxicity should be strictly surveyed throughout radiotherapy.

The impacts of genetic polymorphisms in genes of base excision repair pathway on the efficacy and acute toxicities of (chemo)radiotherapy in patients with nasopharyngeal carcinoma.

PurposeTo explore whether polymorphisms in base excision repair (BER) pathway genes are predictors of (chemo)radiotherapy outcome in patients with nasopharyngeal carcinoma (NPC).MethodsWe genotyped five potentially functional single nucleotide polymorphisms (SNPs) of three genes in the BER pathway in 174 NPC patients who were treated with (chemo)radiotherapy. Sequenom MassArray was used for SNPs analysis. The efficacy at the end of radiotherapy and at 3 months after radiotherapy was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST). Acute radiation toxicity was scored using Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer (RTOG/EORTC) acute radiation morbidity scoring criteria. Logistic regression was employed to assess the multivariate analyses.ResultsWe found that the wide genotype GG of X-ray repair cross-complementing 1 (XRCC1) rs25489 (GG vs GA: OR=3.833, 95%CI=1.512-9.714, P=0.005; GG vs GA+AA: OR=3.610, 95%CI=1.496-8.713, P=0.004) and the wide genotype CC of 8-oxoguanine DNA glycosylase (OGG1) rs1052133 (CC vs GG: OR=0.263, 95%CI=0.073-0.951, P=0.042; CC vs CG+GG: OR=0.454, 95%CI=0.195-1.053, P=0.066) were positively and negatively associated with primary tumor efficacy at the end of radiotherapy, respectively. By contrast, no association was found between BER gene polymorphisms and the treatment outcomes at 3 months post-treatment or the treatment-related acute toxicities.ConclusionsThe SNPs of the BER genes may act as biomarkers for the curative effect of (chemo)radiotherapy. Further study with long-time follow-up and large population is needed for accurate assessment.

Comorbidities and intensity-modulated radiotherapy with simultaneous integrated boost in elderly breast cancer patients.

To evaluate the impact of comorbidity assessment on compliance to intensity modulated radiotherapy with simultaneous integrated boost (SIB-IMRT) in elderly patients affected by early stage breast cancer (BC). 40 consecutive patients were treated with SIB-IMRT (50Gy in 25 fractions to the whole breast, and simultaneously 60Gy to the surgical bed) for invasive BC after conserving surgery. Inclusion criteria were: age ≥ 70years, pT1-2 disease, pN0-1, no neoadjuvant chemotherapy, non-metastatic disease. Charlson comorbidity index was used for comorbidity evaluation. Median follow-up was 44months. At the time of the analysis, OS and LC rates were 100%. All patients completed the SIB-IMRT without interruptions. Acute skin toxicity was recorded as follows: grade 0 in 5 patients (12.5%), grade 1 in 25 cases (62.5%), and grade 2 in 10 patients (25%). Regarding late adverse events, skin toxicity was registered as follows: grade 0 in 27 patients (67.5%) and grade 1 in 13 cases (32.5%). No toxicity ≥grade 2 was registered. At statistical analysis, the presence of comorbidities and the breast volume >700cc were related to skin grade 2 acute toxicity (p = 0.01, p = 0.04). In terms of cosmetic results, 98 and 2% of patients considered the result as good/excellent and as fair after RT, respectively. No patients had a poor cosmetic outcome. The present study showed the feasibility of SIB-IMRT in early stage BC elderly patients and that the absence of comorbidity reduced the risk of acute radiation toxicity.

Dose escalation by image-guided intensity-modulated radiotherapy leads to an increase in pain relief for spinal metastases: a comparison study with a regimen of 30 Gy in 10 fractions.

PurposeUnder the existing condition that the optimum radiotherapy regimen for spinal metastases is controversial, this study investigates the benefits of dose escalation by image-guided intensity-modulated radiotherapy (IG-IMRT) with 60–66 Gy in 20–30 fractions for spinal metastases.ResultsIn the dose-escalation group, each D50 of planning gross tumor volume (PGTV) was above 60 Gy and each Dmax of spinal cord planning organ at risk volume (PRV) was below 48 Gy. The median biological effective dose (BED) of Dmax of spinal cord was lower in the dose-escalation group compared with that in the 30-Gy group (69.70 Gy vs. 83.16 Gy, p < 0.001). After one month and three months of the radiotherapy, pain responses were better in the dose-escalation group than those in the 30-Gy group (p = 0.005 and p = 0.024), and the complete pain relief rates were respectively 73.69% and 34.29% (p = 0.006), 73.69% and 41.38% (p = 0.028) in two compared groups. In the dose-escalation group, there is a trend of a longer duration of pain relief, a longer overall survival and a lower incidence of acute radiation toxicities. No late radiation toxicities were observed in both groups.Materials and MethodsDosimetric parameters and clinical outcomes, including pain response, duration of pain relief, radiation toxicities and overall survival, were compared among twenty-five metastatic spinal lesions irradiated with the dose-escalation regimen and among forty-four lesions treated with the 30-Gy regimen.ConclusionsConventionally-fractionated IG-IMRT for spinal metastases could escalate dose to the vertebral lesions while sparing the spinal cord, achieving a better pain relief without increasing radiation complications.