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Purpose: To evaluate whether intraoral devices reduce the adverse oral and dental effects of radiotherapy in head and neck cancer patients. Materials and Methods: A systematic search of the Medline and Embase databases for articles published before March 2019 was performed by two independent reviewers. Studies published in English that evaluated whether intraoral devices reduced the risk of radiotherapy-related complications in patients receiving radiotherapy in the head and neck region were included. The kappa statistic was used to calculate the level of inter-reviewer agreement. Results: Five studies met the inclusion criteria, although only one was considered to be a low risk of bias. One study reported that intraoral devices did not reduce the severity of mucositis after 7 weeks. The remaining four studies reported that intraoral devices reduced the risk of xerostomia, mucositis, trismus, dysphagia, and dental caries over 2 to 6 months. Conclusion: There are limited data to support the use of intraoral devices in head and neck cancer patients undergoing radiotherapy. Well-designed clinical studies that consider long-term outcomes are necessary to draw definitive conclusions. [ABSTRACT FROM AUTHOR]

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Introduction: The most common adverse effect in postoperative breast radiation therapy, following breast conserving surgery, is acute radiodermatitis, that can cause pauses during RT and affect patients quality of life. There is no adequate prevention for acute radiodermatitis and an individual approach is important in patient’s treatment. The Aim: Aim of this study is evaluation of factors that may influence the acute radiodermatitis onset during and 90 days after breast cancer postoperative irradiation. Material-Methods: In the Center for Radiation Oncology, University Clinical Center Kragujevac, during 2023, the retrospective analysis included 102 female breast cancer patients, treated with postoperative breast irradiation. The data was obtained form medical medical histories. Results: All patients underwent breast conserving surgery with sentinel lymph node biopsy (37.5%) or axillary dissection (62.5%). Moderately hypofractionated regime received 30.6% patient, versus the conventional regimen (69.4%), and 34.7% had a boost, while in 21.2% of cases lymph nodal irradiation was also performed. Acute radiodermatitis was registered in 72.6% cases (62.3% grade 1, 31.9% grade 2 and 5.8% grade 3). The primary tumor characteristics, patient’s habits and systemic therapy had no statistically significant influence on the appearance of acute radiodermatitis. In patients whose skin thickness, before starting radiotherapy, was greater than 4 mm (p=0.0001) or breast volume larger than 1000 cm3 (p=0.038), acute radiodermatitis was registered significantly more often. Conclusion: This results can single out patients at increased risk for the acute radiodermatitis development and help selecting those patients in whom intensified monitoring is necessary. [ABSTRACT FROM AUTHOR]

Atypical vascular lesion (AVL) is an uncommon, benign vascular proliferation seen in previously irradiated skin, most commonly after radiotherapy for breast cancer. Atypical vascular lesion and angiosarcoma may share overlapping clinical and histopathologic features. We report the first case of AVL occurring outside the field of radiation. This patient's clinical course and histopathology was overall consistent with AVL, including two biopsies with focal MYC positivity. However, due to variations in the interpretation of her histopathology, the management plans devised by two centers involved in her care were widely discordant and she was treated with chemotherapy and extensive surgery for angiosarcoma. Great care must be taken to distinguish between these entities, as treatment for angiosarcoma may be associated with significant morbidity. [ABSTRACT FROM AUTHOR]

Objective: Radiation enteritis (RE) is one of the most common radiation-induced toxicities in patients with cervical cancer undergoing pelvic radiotherapy. This study aimed to evaluate predisposing factors for RE in patients with cervical cancer. Methods: In total, 414 patients with cervical cancer undergoing radiotherapy were retrospectively enrolled from Anhui Provincial Cancer Hospital. We col-lected data on age; body mass index; International Federation of Gynecology and Obstetrics stage (I--IV); histology; fasting blood glucose levels; chemotherapy regimen; radiation dose; and histories of hypertension, diabetes mellitus, and surgery. Univariate and multivariate Cox regression analyses were used to assess possible predisposing factors for RE. Results: Incidences of acute RE (ARE) and chronic RE (CRE) were 65.2% and 13.1%, respectively. No prior surgery, radi-ation dose ≥56 Gy, hypertension, and hyperglycemia were found to be independent risk factors for ARE (95% confidence interval [CI], p< 0.05). Hypertension, diabetes mellitus, and hyperglycemia were independent risk factors for CRE (95% CI, p≤ 0.01). Significantly higher incidences of ARE (90.6% vs. 75.8%, p < 0.001) and CRE (62.5% vs. 21.2%, p = 0.001) were found in patients with diabetes mellitus and poor glucose control. Conclusions: To reduce the occurrence of RE in patients with cervical cancer, comorbidities such as diabetes mellitus, hyperglycemia, and hypertension should be controlled, along with consideration of treatment-related factors such as the radio-therapy method and total radiation dose. [ABSTRACT FROM AUTHOR]

Copyright of Bagcilar Medical Bulletin / Bağcılar Tıp Bülteni is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Radiotherapy is a frequently used method for treatment of cancer which is regarded as one of the top two diseases causing premature death worldwide. However, radiotherapy is known to have many side effects. In this study, we evaluated biologically and histologically the possible protective effects of edaravone, the free radical scavenger and neuroprotective agent used to treat amyotrophic lateral sclerosis, on lung and small intestine against radiation-induced early side effects of 15 Gy total body irradiation in single fraction. Thirty-two rats were divided randomly into four equal groups. Groups were administered 15 Gy of external ionizing radiation to the whole body after 30 minutes of EDA administration (a dose of 500 and 50 mg/kg). Rats were sacrified at 72 h of the experiment. Tissues were separated to investigate levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPX) and malondialdehyde (MDA); and evealuate histopathological changings. The protective effect of EDA showed statistically significant in MDA, SOD and GSHPX values of lungs except CAT and statistically significant effect was observed in MDA in small intestine. Also, we showed statistically significant values with histopathological changings. Pediatric cancer patients who have a longer life expectancy are as important as their recovery from their normal life. We are expecting that EDA as a modulator of free radical scavenging pathways in many organs can reduce the side effects of radiation damage on lungs and small intestine. [ABSTRACT FROM AUTHOR]

Le radiothérapeute a un cauchemar : la survenue d'une myélopathie radio-induite. Heureusement, cette complication est exceptionnelle. Son diagnostic est évoqué devant des symptômes cliniques aspécifiques, apparaissant le plus souvent dans les 6 à 24 mois après la radiothérapie, et reste un diagnostic d'exclusion. L'IRM est l'examen paraclinique le plus informatif. Sa physiopathologie reste mal connue, avec une part probable de modifications vasculaires, et une autre part probable de perte de cellules parenchymateuses. Le radiothérapeute porte une attention particulière à la moelle épinière lors de chaque radiothérapie, et plus particulièrement lors de traitements stéréotaxiques ou de réirradiations. L'incidence faible de cette complication rend difficile la prédiction de sa survenue. Classiquement, une dose maximale de 50 Gy est tolérée en radiothérapie normofractionnée (1,8 à 2 Gy par séance). La nécessité clinique de réirradiation dans certaines situations amène parfois le radiothérapeute à outrepasser cette recommandation, en analysant individuellement la balance bénéfice risque. Certains facteurs favorisent la survenue de cette complication et doivent être pris en compte par le radiothérapeute, tels que l'administration de chimiothérapies concomitantes radiosensibilisantes ou neurotoxiques, et certaines comorbidités (diabète). Le développement d'algorithmes prédictifs de cette complication apporte une aide à la décision lors de ces réirradiations. Cependant, le patient doit recevoir une information détaillée des risques encourus lors de ces irradiations à risque, et la prescription du radiothérapeute doit rester prudente. Grâce à l'avènement de l'immunothérapie et des thérapies ciblées, le concept de cancer oligométastatique s'installe progressivement dans la pratique quotidienne, et les traitements stéréotaxiques et les réirradiations seront donc des indications de plus en plus fréquentes. La maîtrise du risque de complications est donc un enjeu majeur dans les années à venir, et reste un défi quotidien pour les radiothérapeutes. Radiation-induced myelopathy is a devastating late effect of radiotherapy. Fortunately, this late effect is exceptional. The clinical presentation of radiation myelopathy is aspecific, typically occurring between 6 to 24 months after radiotherapy, and radiation-induced myelopathy remains a diagnosis of exclusion. Magnetic resonance imaging is the most commonly used imaging tool. Radiation oncologists must be extremely cautious to the spinal cord dose, particularly in stereotactic radiotherapy and reirradiation. Conventionally, a maximum dose of 50 Gy is tolerated in normofractionated radiotherapy (1.8 to 2 Gy per fraction). Repeat radiotherapies lead to consider cumulative doses above this recommendation to offer individualized reirradiation. Several factors increase the risk of radiation-induced myelopathy, such as concomitant or neurotoxic chemotherapy. The development of predictive algorithms to prevent the risk of radiation-induced myelopathy is promising. However, radiotherapy prescription should be cautious, regarding to ALARA principle (as low as reasonably achievable). As the advent of immunotherapy has improved patient survival data and the concept of oligometastatic cancer is increasing in daily practice, stereotactic treatments and reirradiations will be increasingly frequent indications. Predict the risk of radiation-induced myelopathy is therefore a major issue in the following years, and remains a daily challenge for radiation oncologists. [ABSTRACT FROM AUTHOR]

The role and place of a radical hysterectomy in the concept of cervical cancer treatment, despite over one hundred years of its traditional use, still excites controversy. To fully understand the value of the surgical treatment, it is worth analysing and understanding the evolutionary path of the radical hysterectomy and the changes that have occurred in this method over the years. This knowledge will allow for a better understanding as to why the choice of therapy between surgery and radiochemotherapy in the early and locally advanced stages of cervical cancer still raise doubts. Both the introduced changes in the scope of surgery and the use of multi-module treatment - surgery with subsequent radiation therapy did not significantly improve the results of cancer treatment, but significantly increased the prevalence of side effects and therapy complications. As cervical cancer most often affects relatively young women, the number of potential years of life after treatment is high. Over 30% of women in Poland with cervical cancer are in the 45-49 years-old age group. From the perspective of these data, obtaining a high therapeutic index, which is defined as the ratio of the number of healed patients to complications and side effects of treatment significantly reducing the quality of life, is very important in the therapy process. Regardless of the classical radical surgery, which has evolved over many years, a new concept of radical hysterectomy based on tissue morphogenesis, called total mesometrial resection (TMMR) with therapeutic Lymph Node Dissection (tLND) with no adjuvant radiotherapy, has recently been proposed. Based on the ontogenetic research and the study of cancerous tumour development, the concept of TMMR was first introduced by M. Höckel in 2001. In the research conducted by the author, encouraging results of the treatment of stages IB1, IB2, IIA1 and IIA2, and selected cases of stage IIB [according to 2009 International Federation of Gynecology and Obstetrics (FIGO)] cervical cancer were obtained. [ABSTRACT FROM AUTHOR]

Purpose/Objectives: Node-positive breast cancer patients often receive chemotherapy and regional nodal irradiation. The cardiotoxic effects of these treatments, however, may offset some of the survival benefit. Cardiac magnetic resonance (CMR) is an emerging modality to assess cardiac injury. This is a pilot trial assessing cardiac damage using CMR in patients who received anthracycline-based chemotherapy and three-dimensional conformal radiotherapy (3DCRT) regional nodal irradiation using heart constraints. Materials and Methods: Node-positive breast cancer patients (2000–2008) treated with anthracycline-based chemotherapy and 3DCRT regional nodal irradiation (including the internal mammary chain nodes) with heart ventricular constraints (V25 < 10%) were invited to participate. Cardiac tissues were contoured and analyzed separately for whole heart (pericardium) and for combined ventricles and left atrium (myocardium). CMR obtained ventricular function/dimensions, late gadolinium enhancement (LGE), global longitudinal strain (GLS), and extracellular volume fraction (ECV) as measures of cardiac injury and/or early fibrosis. CMR parameters were correlated with dose-volume constraints using Spearman correlations. Results: Fifteen left-sided and five right-sided patients underwent CMR. Median diagnosis age was 50 (32–77). No patients had baseline cardiac disease before regional nodal irradiation. Median time after 3DCRT was 8.3 years (5.2–14.4). Median left-sided mean heart dose (MHD) was 4.8 Gy (1.1–11.2) and V25 was 5.7% (0–12%). Median left ventricular ejection fraction (LVEF) was 63%. No abnormal LGE was observed. No correlations were seen between whole heart doses and LVEF, LV mass, GLS, or LV dimensions. Increasing ECV did not correlate with increased heart or ventricular doses. However, correlations between higher LV mass and ventricular mean dose, V10, and V25 were seen. Conclusion: At a median follow-up of 8.3 years, this cohort of node-positive breast cancer patients who received anthracycline-based chemotherapy and regional nodal irradiation had no clinically abnormal CMR findings. However, correlations between ventricular mean dose, V10, and V25 and LV mass were seen. Larger corroborating studies that include advanced techniques for measuring regional heart mechanics are warranted. [ABSTRACT FROM AUTHOR]

Purpose: Dysphagia is one of the most debilitating chronic symptoms experienced by patients who undergo radiation treatment for head and neck cancer. Despite the high prevalence of dysphagia in patients with head and neck cancer, we lack understanding of the specific changes in swallowing physiology that arise in the short-term following radiation therapy and how these changes impact the key functions of swallowing safety and efficiency. This study sought to identify pathophysiological mechanisms underlying impairments in swallowing safety and efficiency on thin liquids following (chemo)radiation for oropharyngeal cancer. Method: Videofluoroscopic swallowing studies were completed in 12 male patients within 6 months following completion of (chemo)radiation and in 12 healthy male controls. To compare swallowing function and physiology between groups, we analyzed three discrete sips of 20% w/v thin liquid barium per participant. The videofluoroscopic swallowing study recordings were rated for swallowing safety, efficiency, timing parameters, and pixel-based measures of structural area or movement. Results: The oropharyngeal cancer cohort displayed significantly higher frequencies of penetration–aspiration, incomplete laryngeal vestibule closure, prolonged time-to-laryngeal vestibule closure, and poor pharyngeal constriction. Incomplete or delayed laryngeal vestibule closure was associated with airway invasion, while poor pharyngeal constriction was associated with pharyngeal residue. Conclusions: This study highlights the primary mechanisms behind impaired safety and efficiency of the swallow in patients following (chemo)radiation for oropharyngeal cancer. [ABSTRACT FROM AUTHOR]

Radiation‐induced pulmonary fibrosis (RIPF) is a life‐threatening complication of thoracic radiotherapy, which contributes to continued deterioration in pulmonary function. Sphingosine‐1 phosphate receptor 3 (S1PR3) has been identified as a crucial molecule in fibrosis. Accumulating evidence indicated that the inhibition of the S1PRs ameliorates fibrogenesis. Thus, this study aims to explore whether S1PR3 participates in RIPF and elucidates the molecular mechanisms underlying S1PR3‐modulated epithelial–mesenchymal transition (EMT) in transforming growth factor‐β1‐induced pulmonary epithelia. A recombinant adeno‐associated viral‐mediated S1PR3 (AAV‐S1PR3) gene therapy analyzed the effect of S1PR3 gene deficiency on the altered histology structure and molecular mechanisms in the lung of mice with whole‐lung irradiation. Compared with the AAV‐negative control mice, AAV‐mediated S1PR3 knockdown in the lung of mice attenuated pulmonary fibrosis induced by the radiation, as indicated by the alleviation of collagen accumulation, lessened histopathological alterations, and the suppression of inflammatory cells infiltration. S1PR3 deficiency reversed the RIPF concomitantly with abrogated EMT‐related protein (α‐smooth muscle actin). Consistently, S1PR3‐deficient pulmonary epithelia inhibited the EMT process changes and fibrosis formation. Furthermore, S1PR3 was designated as one of the target genes for microRNA‐495‐3p (miR‐495‐3p). The inhibition of miR‐495‐3p promoted the expression of S1PR3 in pulmonary epithelia, whereas the overexpression of miR‐495‐3p inhibited the S1PR3/SMAD2/3 pathway and suppressed the EMT process. Collectively, miR‐495‐3p might be a negative regulator of the EMT process in fibrosis formation by inhibiting the targeted S1PR3 gene. These results established a link between the S1PR3 gene, the EMT process, and the fibrosis, suggesting the pharmacological blockage of S1PR3 as a potential therapeutic strategy for RIPF. [ABSTRACT FROM AUTHOR]

Radiation ulcers are a prevalent toxic side effect in patients receiving radiation therapy. At present, there is still no effective treatment for the complication. Senescent cells accumulate after radiation exposure, which can induce cell and tissue dysfunction. Here we demonstrate increased expression of p16 (a senescence biomarker) in human radiation ulcers after radiotherapy and radiation-induced persistent cell senescence in animal ulcer models. Furthermore, senescent cells secreted the senescence-associated secretory phenotype (SASP) and induced cell senescence in adjacent cells, which was alleviated by JAK inhibition. In addition, the clearance of senescent cells following treatment with a senolytics cocktail, Dasatinib plus Quercetin (DQ), mitigated radiation ulcers. Finally, DQ induced tumor cell apoptosis and enhanced radiosensitivity in representative CAL-27 and MCF-7 cell lines. Our results demonstrate that cell senescence is involved in the development of radiation ulcers and that elimination of senescent cells might be a viable strategy for patients with this condition. [ABSTRACT FROM AUTHOR]

Background: Osteoradionecrosis (ORN) is a complication that occurs after radiotherapy for head or neck malignancies. ORN of the spine is rare, with only few cases affecting the cervical spine reported to date. To our knowledge, no case of lumbar ORN has been reported. We report a rare case of ORN in the lumbar spine that occurred 2 years after radiotherapy and perform a literature review.Case Presentation: We present a case of lumbar ORN that occurred 2 years after radiotherapy for gallbladder carcinoma. The patient was successfully treated conservatively and followed up for > 10 years.Conclusions: ORN of the spine is a rare complication of radiotherapy. Spinal ORN is clinically described as a chronic disease with a slow onset. The most common presenting symptom of spinal ORN is pain. However, as ORN progresses, spinal kyphosis and instability can lead to neurological compression and thus to induced myelopathy or radiculopathy. Treatment of spinal ORN is comprehensive, including orthosis, medication, hyperbaric oxygen therapy, surgery, and new treatment combinations of pentoxifylline and tocopherol. The surgical rate for spinal ORN is relatively high. [ABSTRACT FROM AUTHOR]

Subdural lymphomas are a rare subtype of primary central nervous system lymphomas that can radiographically mimic epidural blood and pose a diagnostic challenge. They can complicate treatment if not preemptively identified. We present a case report of a subdural lymphoma that mimicked a compressive subdural hematoma, and we review the PubMed database for similar cases. A 77-year-old woman presented with a transient left facial droop and what appeared to be a subdural hematoma on computed tomography scan. The patient underwent surgery, during which grossly abnormal solid epicortical adherent tissue was noted instead of the expected appearance of a subdural hematoma. An intraoperative biopsy was suggestive of lymphoma, and the surgery was converted to a craniectomy. Pathology confirmed the diagnosis of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The patient underwent radiotherapy with no complications or recurrence. Magnetic resonance imaging demonstrated complete resolution of the mass at 3 months after treatment, at which time the patient underwent a synthetic cranioplasty. Seven case reports of primary dural lymphomas mimicking subdural blood were found, with variable pathologic subclassifications. Although rare, a primary dural lymphoma can be mistaken for a subdural hematoma on computed tomography scan. The most common subtype is low-grade extranodal marginal zone lymphomas. It is important to keep these diseases in the differential diagnosis, especially when there is incongruence between imaging and the clinical picture, as earlier detection correlates to a stronger therapeutic response. [ABSTRACT FROM AUTHOR]

Oral cancer is the 6th most common cancer in the world. Oral cancer mostly involves the tongue floor of the mouth. The main cause's oral cancers are smoking, alcohol, and human papillomavirus. The more importantly specific hallmarks and features preferably include tongue, mouth, gums. Smoking and chewing tobacco with or without alcohol consumption, and human papillomavirus infections are considered as important etiological factors associated with oral cancer. The major complications in oral cancer patients due to chemo/radiotherapy include dry mouth, cavities, oral communications with sinuses, and difficulty in speaking, eating and drinking. Chemotherapy and radiation treatment moderate or stop the development of new cells. The most common oral complications related to chemo/radiotherapy are bisphosphonate osteonecrosis, dysgeusia, oral fungal and viral infections, osteoradionecrosis, trismus, oral pain, salivary gland and taste dysfunction, rampant dental caries and xerostomia in oral cancer patients. In severe oral toxicities cases, dose reduction or treatment schedule modifications if necessary, treatment should be discontinued. Assessment of oral status, pre-treatment interventions and timely management of lesions, patient education, and identification of high-risk populations before and after chemo/radiotherapy are necessary for the management of above oral complications. [ABSTRACT FROM AUTHOR]

Radiation-induced lymphopenia (RIL) is associated with worse survival in patients with solid tumors, as well as lower response rates to checkpoint inhibitors. While single-fraction total-body irradiation is known to result in exponential decreases in the absolute lymphocyte count (ALC), the kinetics of lymphocyte loss after focal fractionated exposures have not previously been characterized. In the current study, lymphocyte loss kinetics was analyzed among patients undergoing focal fractionated radiotherapy for clinical indications. This registry-based study included 419 patients who received either total-body irradiation (TBI; n = 30), stereotactic body radiation therapy (SBRT; n = 73) or conventionally fractionated chemoradiation therapy (CFRT; n = 316). For each patient, serial ALCs were plotted against radiotherapy fraction number. The initial three weeks of treatment for CFRT patients and the entirety of treatment for SBRT and TBI patients were fit to exponential decay in the form ALC(x) = ae–bx, where ALC(x) is the ALC after x fractions. From those fits, fractional lymphocyte loss (FLL) was calculated as FLL = (1 – e–b) * 100, and multivariable regression was performed to identify significant correlates of FLL. Median linearized R2 when fitting the initial fractions was 0.98, 0.93 and 0.97 for patients receiving TBI, SBRT and CFRT, respectively. In CFRT patients, apparent ALC loss rate slowed after week 3. Fitting ALC loss over the entire CFRT course therefore required the addition of a constant term, "c". For TBI and SBRT patients, treatment ended during the pure exponential decay phase. Initial FLL varied significantly with treatment technique. Mean FLL was 35.5%, 24.3% and 10.77% for patients receiving TBI, SBRT and CFRT, respectively (P < 0.001). Significant correlates of FLL varied by site and included field size, dose per fraction, mean spleen dose, chemotherapy backbone and age. Finally, total percentage ALC loss during radiotherapy was highly correlated with FLL (P < 0.001). Lymphocyte depletion kinetics during the initial phase of fractionated radiotherapy are characterized by pure exponential decay. Initial FLL is strongly correlated with radiotherapy planning parameters and total percentage ALC loss. The two groups with the highest FLL received no concurrent chemotherapy, suggesting that ALC loss can be a consequence of radiotherapy alone. This work may assist in selecting patients for adaptive radiotherapy approaches to mitigate RIL risk. [ABSTRACT FROM AUTHOR]

Purpose: External beam radiotherapy (EBRT) is a useful option to treat head and neck skin cancer patients who are not indicated for surgery. In this study, we evaluated the treatment outcomes of EBRT in an Asian population. Materials and Methods: The records from 19 head and neck skin cancer patients (10 with squamous cell carcinoma and 9 with basal cell carcinoma) who were treated with definitive or adjuvant EBRT from 2009 to 2017 were retrospectively reviewed. The radiotherapy doses administered ranged from 50 to 66 Gy (median, 55 Gy) with 2.0-2.75 Gy per daily fraction (median, 2.5 Gy). The T stage at presentation was as follows: Tis (1 patient), T1 (11 patients), T2 (6 patients), and T3 (1 patient). None had regional lymph node disease or distant metastasis at presentation. The local failure-free survival (LFFS) rates, toxicity, and cosmetic results were analyzed. Results: The median age was 75.5 years (range, 52.6 to 92.5 years). The median follow-up duration from the completion of radiotherapy was 44.9 months (range, 5.8 to 82.6 months). One local failure occurred in a patient with a 2.1-cm posterior neck squamous cell carcinoma at 32.5 months after radiotherapy (1/19, 5.3%). The 3-year LFFS rate was 91.7%. No patients died from skin cancer during follow-up, and no grade 3 complications occurred. The cosmetic outcomes were excellent for 16 (84.2%) and good for 3 (15.8%) of the 19 patients. Conclusion: EBRT offers good local control and cosmetic outcomes in patients with head and neck skin cancer, with no grade 3 complications. [ABSTRACT FROM AUTHOR]

Hyposalivation is a frequent complication after treatment with radiotherapy. To evaluate the efficacy of transcutaneous electrical nerve stimulation (TENS) on the hyposalivation assessed through stimulated salivary flow (SSF). In this clinical trial, 68 patients (with hyposalivation) were randomly assigned to control (n = 31) or TENS (n = 37) group. Participants in control group received habitual care, while those in TENS group received 8 sessions (20 minutes each) delivered twice a week for four weeks. The electrodes were attached over the skin covering the salivary glands. The electric pulse was adjusted at a frequency of 50 Hz, pulse width of 250 μs and as intense as tolerated. SSF was evaluated through sialometry. Self‐perception of salivary flow (SPSF) and quality of life (QL) was evaluated prior to, during and at 1, 3 and 6 months after treatment. Although no changes were observed in the control group for SSF at any timepoints, TENS group showed a progressive increase in SSF from the third session until the end of the treatment. Significant improvements were also found in SPSF, especially when the SSF reached values ≥0.7 mL/minute. The most expressive results were evident at 6 months after treatment so that SSF, SPSF and QL remained significantly higher (F = 9.5, P = 0.0001; H = 143.77, P < 0.0001; χ2 = 9.162, P = 0.02, respectively). TENS was effective at improving hyposalivation. The benefits on SSF, SPSF and QL give base to a promising therapeutic strategy for patients with hyposalivation after radiotherapy treating head and neck cancer. [ABSTRACT FROM AUTHOR]

Background: Exposure of nontarget organs such as the thyroid gland (as a normal and high radiosensitive tissue) to radiation during radiotherapy for patients with head-and-neck cancers remains unavoidable. Hypothyroidism is the most common radiation side effect on the thyroid gland. In this study, we used the parameters of thyroid gland (triiodothyronine [T3], thyroxine [T4], and thyroid-stimulating hormone [TSH]) measurements before and after radiotherapy for patients with head-and-neck cancers. Materials and Methods: In the first step, descriptive statistics for predictors and response variables were performed. In the next step of data analysis, a multivariate linear mixed-effects model was fitted simultaneously for three response variables in order to study the trend of thyroid gland parameters. Results: The results indicated that there was a significant decreasing trend in TSH from 1.74 at baseline to 0.65 at the end of the study, and there was a significant increasing trend in T4 from 8.63 at baseline to 9.38 at the end of the study. Conclusions: There were significant changes in thyroid gland parameters after radiotherapy treatment for patients with head-and-neck cancers. Thus, preventative strategies are needed to reduce this complication. The patients with head-and-neck cancers who received radiotherapy treatment should be evaluated regularly and repeatedly during the radiotherapy treatment period. [ABSTRACT FROM AUTHOR]

Radiation-induced acute skin injury and consequent fibrosis are common complications of cancer radiotherapy and radiation accidents. Stromal cell-derived factor-1α (SDF-1α) and its receptor, CXC chemokine receptor 4 (CXCR4) have been shown to be involved in multiple cellular events. However, the role of SDF-1α/CXCR4 axis in radiation-induced acute injury and fibrosis of skin has not been reported. In this study, we found that the expression of SDF-1α and CXCR4 was significantly increased in irradiated skin tissues of humans, monkeys and rats, compared to their nonirradiated counterparts. Mice with keratinocyte-specific ablation of CXCR4 showed less severe skin damage than wild-type mice after receiving a 35 Gy dose of radiation. Consistently, subcutaneous injection of AMD3100, an FDA approved SDF-1α/CXCR4 inhibitor, attenuated skin injury and fibrosis induced by exposure to radiation in a rat model. Mechanically, the SDF-1α/CXCR4 axis promotes pro-fibrotic TGF-b/Smad signaling through the PI3K-MAPK signaling cascade in human keratinocyte HaCaT cells and skin fibroblast WS1 cells. AMD3100 inhibited Smad2 nuclear translocation and transcriptional activity of Smad2/3 induced by radiation, which suppressed the pro-fibrotic TGF-b/Smad signaling pathway activated by exposure. Taken together, these findings demonstrate the involvement of SDF-1α/CXCR4 axis in radiation-induced acute injury and fibrosis of skin, and indicate that AMD3100 would be an effective countermeasure against these diseases. [ABSTRACT FROM AUTHOR]

Background: Skin cancer is common after radiotherapy among childhood cancer survivors (CCSs). We studied risks and risk factors for subsequent skin cancers, with emphasis on radiation dose, exposed skin surface area, and chemotherapeutic agents.Methods: The DCOG-LATER cohort study includes 5-year Dutch CCSs diagnosed 1963-2001. Subsequent skin cancers were identified from record linkages with the Netherlands Cancer Registry and Dutch Pathology Registry. Incidence rates were compared with general population rates. Multivariable Cox regression models were used, applying a novel method of case-control sampling enabling use of tumor location in cohort analyses. All statistical tests were two-sided.Results: Among 5843 CCSs, 259 developed 1061 basal cell carcinomas (BCCs) (standardized incidence ratio [SIR] = 29.8, 95% confidence interval [CI] = 26.3 to 33.6; excess absolute risk per 10 000 person-years (EAR) = 24.6), 20 had melanoma (SIR = 2.3, 95% CI = 1.4 to 3.5; EAR = 1.1), and 10 had squamous cell carcinoma (SIR = 7.5, 95% CI = 3.6 to 13.8; EAR = 0.8). Cumulative incidence of BCC 40 years after childhood cancer was 19.1% (95% CI = 16.6 to 21.8%) after radiotherapy vs 0.6% expected based on general population rates. After a first BCC, 46.7% had more BCCs later. BCC risk was associated with any radiotherapy to the skin compartment of interest (hazard ratio [HR] = 14.32, 95% CI = 10.10 to 20.29) and with estimated percentage in-field skin surface area (26-75%: HR = 1.99, 95% CI = 1.24 to 3.20; 76-100%: HR = 2.16, 95% CI = 1.33 to 3.53, vs 1-25% exposed; Ptrend among exposed = .002), but not with prescribed radiation dose and likelihood of sun-exposed skin-area. Of all chemotherapy groups examined, only vinca alkaloids increased BCC risk (HR = 1.54, 95% CI = 1.04 to 2.27).Conclusion: CCSs have a strongly, 30-fold increased BCC risk. BCC risk appears to increase with increasing skin surface area exposed. This knowledge underscores the need for awareness by survivors and their health care providers. [ABSTRACT FROM AUTHOR]

• The amygdala is critical to emotional processing, fear recognition, and memory. • We measured amygdala volumes in brain tumor patients treated with radiation (RT). • RT dose-dependent amygdala atrophy was observed at 1 year after treatment. • Amygdala atrophy after brain RT may contribute to neuropsychological deficits. The amygdalae are deep brain nuclei critical to emotional processing and the creation and storage of memory. It is not known whether the amygdalae are affected by brain radiotherapy (RT). We sought to quantify dose-dependent amygdala change one year after brain RT. 52 patients with primary brain tumors were retrospectively identified. Study patients underwent high-resolution, volumetric magnetic resonance imaging before RT and 1 year afterward. Images were processed using FDA-cleared software for automated segmentation of amygdala volume. Tumor, surgical changes, and segmentation errors were manually censored. Mean amygdala RT dose was tested for correlation with amygdala volume change 1 year after RT via the Pearson correlation coefficient. A linear mixed-effects model was constructed to evaluate potential predictors of amygdala volume change, including age, tumor hemisphere, sex, seizure history, and bevacizumab treatment during the study period. As 51 of 52 patients received chemotherapy, possible chemotherapy effects could not be studied. A two-tailed p -value <0.05 was considered statistically significant. Mean amygdala RT dose (r = −0.28, p = 0.01) was significantly correlated with volume loss. On multivariable analysis, the only significant predictor of amygdala atrophy was radiation dose. The final linear mixed-effects model estimated amygdala volume loss of 0.17% for every 1 Gy increase in mean amygdala RT dose (p = 0.008). The amygdala demonstrates dose-dependent atrophy one year after radiotherapy for brain tumors. Amygdala atrophy may mediate neuropsychological effects seen after brain RT. [ABSTRACT FROM AUTHOR]

A significant complication of radiotherapy to the head and neck for cancer treatment is osteoradionecrosis (ORN) of the jaws. The management of ORN can be complex and often requires a multimodality approach. Nonsurgical treatments with or without adjunct measures and surgical interventions have all been employed on the basis of the staging of the disease process. New theories on the pathophysiology of ORN have led to the identification of novel treatment modalities. ORN is a major complication of surgery or trauma in previously irradiated bone in the absence of tumor persistence. Radiation-induced vascular insufficiency rather than infection causes bone death. It occurs most commonly in the mandible after head and neck irradiation. Risk factors include the total radiation dose, modality of treatment, fraction size and dose rate, oral hygiene, timing of tooth extractions as well as the continued use of tobacco and alcohol. This condition is often painful, debilitating, and may result in significant bone loss. In the past, tissue hypoxia and its consequences were accepted as the primary cause, and this led to the use of hyperbaric oxygen for both treatment and prevention of complications of radiotherapy in the head and neck. [ABSTRACT FROM AUTHOR]

The article discusses the oral and dental complications induced by radiation and chemotherapy and their management to cancer patients. It states that the most severe complication that can occur with radiation therapy is osteoradionecrosis. Meanwhile, the dental problems associated with chemotherapy are periodontal disease, pulp necrosis and prolonged or spontaneous oral bleeding. However, patients who have undergone radiation therapy, chemotherapy and anatomical change face a degree of chronicity due to surgery.

The article presents a case study of advanced imaging findings in stroke‑like migraine attacks after radiation therapy (SMART) syndrome in a survivor of high-grade glioma with progressive cephalgia and expressive aphasia. Topics include brain-directed radiotherapy, improved diagnostic accuracy and tumor recurrence.

Background/Purpose: Limited evidence has been obtained on varicella-zoster virus (VZV) infection in patients with breast cancer as a complication related to adjuvant radiotherapy. We conducted a cohort study aimed to assess the risk of VZV infection in this patient setting. Materials and methods: We used the National Health Insurance Research Database to identify 65,981 patients with breast cancer in Taiwan who underwent breast surgery between 2000 and 2011. After a 1:1 propensity score match was obtained between patients with and without radiotherapy, a competing risk regression model was constructed to estimate the hazard ratios and the incidence rate difference (IRD) of VZV infection in the patients with breast cancer receiving radiotherapy and those not receiving radiotherapy. Results: After adjusting for covariates, the radiotherapy cohort showed a 1.51-fold higher risk (95% confidence interval = 1.06–5.16, p = 0.02, IRD = 4.98/10000 person-years) of subsequent VZV infection than the nonradiotherapy cohort. Furthermore, VZV infection risk was 3.85-fold higher among patients aged >65 years who received radiotherapy than among those of the same age who did not receive radiotherapy (95% confidence interval = 1.1–13.4, p < 0.05, IRD = 11.09/10000 person-years). The risk increased with adjusted hazard ratio of 6.6 (95% confidence interval I = 1.51–28.8, p < 0.05, IRD = 32.01/10,000 person-years) and 7.08 (95% confidence interval = 1.64–30.5, p < 0.01, IRD = 35.72/10,000 person-years) in follow-up period less than 3 months and 3–5 months respectively. Conclusion: Radiotherapy was associated with an increased risk of VZV infection among patients with breast cancer. The risk was significantly higher in older patient (>65 years old) and/or those who received chemotherapy. Regular clinical follow-up and additional serological testing in the first 5 months after radiotherapy are recommended. [ABSTRACT FROM AUTHOR]

Prior studies have shown that dose-escalated radiation therapy for prostate cancer improves clinical outcomes. However, this is associated with increased rectal toxicity. Hydrogel spacer for prostate cancer therapy is an effective way of decreasing rectal toxicity in the late post-therapeutic stages. In some occasions, the gel spacer may not be placed symmetrically between the rectum and prostate. There are several forms of a malpositioned spacer, including lateral displacement, rectal wall infiltration, and prostate capsule infiltration. This manuscript is aimed at evaluating appropriately positioned and malpositioned gel spacers, primarily via magnetic resonance imaging. There are limited educational imaging guides that address what radiologists should evaluate on post-spacer placement imaging. This pictorial review will specifically evaluate post-injection pitfalls such as asymmetry, rectal wall infiltration, and subcapsular injection. [ABSTRACT FROM AUTHOR]

Objective: To assess whether radiotherapy (RT) for prostate cancer (PCa) was a risk factor for secondary bladder cancer (BLCa) through a meta-analysis. Materials and methods: The MEDLINE, Embase, and the Cochrane Library were systematically searched for all studies investigating the risk of BLCa in patients with RT. The association between RT and risk of BLCa was summarized using hazard ratio with a 95%CI. The protocol for this meta-analysis is available from PROSPERO (CRD42018090075). Results: Overall, 619,479 participants (age: 57–79 years) were included from 15 studies, 206,852 of whom were patients who received RT. Synthesis of results indicated that RT was significantly associated with an increased risk of BLCa compared with the risk in those who received radical prostatectomy or non-RT (overall HR=1.6, 95%CI: 1.33–1.92, P<0.001). The results were consistent when restricted to a 5-year lag period (HR=1.84, 95%CI: 1.26–2.69, P=0.002) and multivariable adjustment (HR=1.96, 95%CI: 1.47–2.62, P<0.001), but not for 10-year lag period (HR=1.93, 95%CI: 0.9– 4.16, P=0.093) and brachytherapy subgroup (HR=1.33, 95%CI: 0.87–2.05, P=0.188). The GRADE-profiler revealed that the rate of events of BLCa on average in the RT-patients and the non-RT control was 2,462/183,669 (1.3%) and 4,263/382,761(1.1%), respectively; the overall quality of the evidence was low. Conclusion: Patients who received RT for PCa was associated with higher risks of developing secondary BLCa compared to those unexposed to RT, but the absolute effect was low. [ABSTRACT FROM AUTHOR]

Background and purpose The high plasticity of the intestinal epithelium is maintained by a resilient reserve stem cell population, whose extent and biology are a matter of ongoing debate. The in vivo clonogenic assay (IVCA), presents a well established and efficient analysis of radiation insult to the intestinal crypts. However, we found that inadequate mathematical analysis over the last four decades led to systematic errors and contradictory results in estimates of radio-sensitivity and size of the reserve stem cell pool. Material and methods We devised a refinement of the IVCA via development of a biomathematical model that delivers a full statistical dynamic description of epithelial radiation injury and subsequent regeneration. We validated the model against cellular and crypt distribution statistics obtained from IVCA experiments and through systematic re-analysis of experimental data from 27 publications. Results A full dynamic description of the evolution of stem cell niche population statistics is obtained. A systematic re-analysis reveals a consistent clonogenic content of the crypt of 31 ± 6 cells. The stem cell reserve manifests to be, contrary to prior predictions, radio-resistant: α = (0.22 ± 0.04) Gy−1. Conclusion We established a precision tool for the quantitative analysis of radiation insult to the intestinal crypts, which we employ to show that the reserve stem cell population is small, radio-resistant, and remarkably immutable against a large variety of interventions. The increased resolution of the model allows not only a reduction of the number of animals by about 75%, but also to quantify experimentally the influence of additional agents on damage and on regeneration of the stem cell niche. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to validate a previously published predictive model for late fecal incontinence (FI) in a contemporary population of prostate cancer patients treated with radical radiation therapy.Methods and Materials: The validation included patients treated with intensity-modulated radiation therapy (IMRT) (2010-2014). Prescribed dose range was 65-80 Gy, including conventional and moderate hypo-fractionated treatments. Rectal toxicity was scored using LENT/SOMA, a minimum 2-year follow up was considered. We chose to validate the model published by Rancati et al for predicting chronic FI, developed on a 3-dimensional conformal radiation therapy (3DCRT) population. It considered a longitudinal endpoint defined as the average toxicity grade during the follow up. This continuous endpoint was dichotomized using a cut-off value of mean FI grade >1. The model included mean rectal dose (Dmean), previous diseases of the colon (COLO) and previous abdominal surgery (SURG). Doses were corrected to 2 Gy/fraction using the linear-quadratic model and applying alpha/beta ratio = 4.8 Gy.Results: 228 patients constituted the validation population. A mean FI grade >1 was scored in 25 patients (11%). Logistic regression confirmed risk factors reported in the literature, with similar odds ratios (ORs) for Dmean (1.04 ± 0.03 vs 1.06 ± 0.04) and SURG (1.9 ± 1.7 vs 1.6 ± 1.45); COLO was not confirmed. Consequently, the predictive models including Dmean/Dmean + SURG were evaluated using calibration plots. Both showed a clear discriminative trend, but the absolute observed toxicity rates were underestimated (ie, absolute predicted rates were always lower than corresponding absolute observed rates). This result was consistent with an unexpected effect of hypofractionation (OR = 2.20, conventional = 8.1% vs hypofractionated = 17.4%) beyond the standard correction using linear-quadratic model. Nevertheless, the FI rate in the conventionally treated group was almost double the rate observed in the previously studied cohort (4.3% vs 8.1%).Conclusions: The study confirms previously published results indicating that abdominal surgery and rectal mean dose are risk factors for late FI. Calibration plots highlight a possible role of hypofractionation beyond linear-quadratic correction. [ABSTRACT FROM AUTHOR]

Introduction: Oral mucositis (OM) is a major dose-limiting side effect of chemotherapy and radiation used in cancer treatment. Due to the complex nature of OM, currently available drug-based treatments are of limited efficacy.Objectives: Our objectives were (i) to determine genes and molecular pathways associated with OM and wound healing using computational tools and publicly available data and (ii) to identify drugs formulated for topical use targeting the relevant OM molecular pathways.Methods: OM and wound healing-associated genes were determined by text mining, and the intersection of the two gene sets was selected for gene ontology analysis using the GeneCodis program. Protein interaction network analysis was performed using STRING-db. Enriched gene sets belonging to the identified pathways were queried against the Drug-Gene Interaction database to find drug candidates for topical use in OM.Results: Our analysis identified 447 genes common to both the "OM" and "wound healing" text mining concepts. Gene enrichment analysis yielded 20 genes representing six pathways and targetable by a total of 32 drugs which could possibly be formulated for topical application. A manual search on ClinicalTrials.gov confirmed no relevant pathway/drug candidate had been overlooked. Twenty-five of the 32 drugs can directly affect the PTGS2 (COX-2) pathway, the pathway that has been targeted in previous clinical trials with limited success.Conclusions: Drug discovery using in silico text mining and pathway analysis tools can facilitate the identification of existing drugs that have the potential of topical administration to improve OM treatment. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the rate of and identify risk factors for vasculopathy after proton therapy in pediatric patients with central nervous system and skull base tumors.Methods and Materials: Between 2006 and 2015, 644 pediatric patients with central nervous system and skull base tumors were treated with proton therapy at a single institution. The 3 most common histologies were craniopharyngioma (n = 135), ependymoma (n = 135), and low-grade glioma (n = 131). The median age was 7.6 years (range, 0.7-21.8 years), and the median prescribed dose was 54 cobalt gray equivalent (CGE) (range, 25.2-75.6 CGE). For this analysis, vasculopathy included asymptomatic vessel narrowing identified on imaging, transient ischemic attacks, and cerebrovascular accidents. Serious vasculopathy was defined as events resulting in permanent neurologic complications or requiring revascularization surgery. Multivariate logistic regression (MVA) was used to assess predictors of toxicity. Variables examined included age, neurofibromatosis, extent of surgical resection, chemotherapy, postoperative stroke, total prescribed dose, and dose delivered to the optic nerves, chiasm, and hypothalamus.Results: With a median follow-up of 3.0 years (range, 0.1-9.6 years), the 3-year cumulative rates of any vasculopathy and serious vasculopathy were 6.4% and 2.6%, respectively. Seven children (1.2%) experienced a stroke with permanent neurologic deficits; 4 required revascularization surgery. On MVA, maximum dose to the optic chiasm ≥ 54 CGE was significantly associated with the development of any vasculopathy (13.1% vs 2.2%; P < .001); age < 5 years was also significant (8.4% vs 5.4%; P < .01). On MVA, maximum dose to the optic chiasm ≥ 54 CGE also predicted serious vasculopathy (3.8% vs 1.7%; P < .05).Conclusions: Childhood cancer survivors are at risk of vasculopathy after cranial radiation therapy. Young children and those receiving ≥54 CGE to the chiasm are at an increased risk of this toxicity. These findings suggest appropriate follow-up and screening are important in this population. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy is an important and the most common treatment modality for human cancers. Cancer radiotherapy is associated with unadorned side effects that results from normal tissue damage which is a major subject of concern. Radiation induces damage to living cells due generation of aqueous-free radicals. Therefore, there is a crucial need for the protection of normal cells surrounding the tumor from radiation injury; and hence, the identification of radiation-protecting agents is a chief goal for basic radiation biologists and oncologists. Aim: The aim of this present study was to assess the radioprotective potential of Asparagus racemosus root ethanolic extract (ARE), and isoprinosine (IPR) against electron beam radiation (EBR)-induced immunosuppression and oxidative stress in Swiss Albino mice. Materials and Methods: Swiss albino mice were used for the assessment of the radioprotective potential of ARE and IPR against EBR-induced immunosuppression and oxidative stress. Cytokine estimations, namely, interleukin-2, interferon-gamma, and tumor necrosis factor-alpha were performed in the liver homogenate using ELISA kits, and bone marrow cellularity was determined in the experimental animals. Results: The results of the present study demonstrated the radioprotective and immunostimulatory efficacy of ARE and IPR against EBR-induced cytokine and bone marrow cellularity alterations. Conclusion: The findings of our study demonstrate the potential of ARE and IPR in mitigating radiation-induced mortality by offering protection to mice against lethal dose of whole body EBR. The present study also demonstrates that ARE and IPR exert its radioprotection against EBR induced immunosuppression by regulating cytokines. [ABSTRACT FROM AUTHOR]

Purpose: A 2-arm, double-blinded randomized trial was conducted to evaluate the efficacy of 0.1% mometasone furoate (MF) versus Eucerin Original (E) cream in preventing the development of moderate to severe acute radiation dermatitis (ARD) in breast cancer patients receiving postmastectomy radiation (PMRT).Methods: Breast cancer patients undergoing chest wall with or without nodal radiation therapy (RT) (50 Gy) were eligible. Randomization (1:1) was to MF or E, applied twice daily from day 1 of PMRT to 14 days after PMRT. Patients were stratified by RT technique, body mass index, and reconstruction status. Daily bolus of 3 to 10 mm was applied in all patients. The primary endpoint was the development of provider-assessed grade ≥2 (Common Terminology Criteria for Adverse Events version 4.03) ARD with moist desquamation or any grade ≥3 dermatitis. Secondary endpoints were time to occurrence of maximum-grade dermatitis and patient-reported skin symptoms using a skin-related quality of life questionnaire, Skindex-16. Assessments were performed at baseline, weekly during PMRT, and 2 weeks after PMRT.Results: 124 patients were enrolled between May 2013 and February 2016. Of those, 35% had pathologic stage III disease, 6% had cT4d disease, and 68% underwent reconstruction. Sixty percent received 3-dimensional conformal RT with photons only to the chest wall, 18% received electrons and photons, and 23% received inverse-planned intensity modulated RT. Groups were well balanced for age, skin type, and stage. The rate of moist desquamation was 54.8% in the entire cohort, with a significantly reduced incidence in the MF arm than in the E arm (43.8% vs 66.7%; P = .012). The MF arm had a lower incidence of maximum skin toxicities (P = .036) and longer time to development of grade 3 dermatitis (46 days vs 35.5 days, respectively; P ≤ .001). There was no difference in patient-reported skin outcomes between arms.Conclusions: Breast cancer patients receiving MF during PMRT experienced significantly reduced rates of moist desquamation in comparison with a control cream. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the impact of postmastectomy radiation therapy (PMRT) for patients with T1-T2 tumors and 1 to 3 positive lymph nodes enrolled on the Breast International Group (BIG) 02-98 trial.Methods and Materials: The BIG 02-98 trial randomized patients to receive adjuvant anthracycline with or without taxane chemotherapy. Delivery of PMRT was nonrandomized and performed according to institutional preferences. The present analysis was performed on participants with T1-T2 breast cancer and 1 to 3 positive lymph nodes who had undergone mastectomy and axillary nodal dissection. The primary objective of the present study was to examine the effect of PMRT on risk of locoregional recurrence (LRR), breast cancer-specific survival, and overall survival.Results: We identified 684 patients who met the inclusion criteria and were included in the analysis, of whom 337 (49%) had received PMRT. At 10 years, LRR risk was 2.5% in the PMRT group and 6.5% in the no-PMRT group (hazard ratio 0.29, 95% confidence interval 0.12-0.73; P = .005). Lower LRR after PMRT was noted for patients randomized to receive adjuvant chemotherapy with no taxane (10-year LRR: 3.4% vs 9.1%; P = .02). No significant differences in breast cancer-specific survival (84.3% vs 83.9%) or overall survival (81.7% vs 78.3%) were observed according to receipt of PMRT.Conclusion: Our analysis of the BIG 02-98 trial shows excellent outcomes in women with T1-T2 tumors and 1 to 3 positive lymph nodes found in axillary dissection. Although PMRT improved LRR in this cohort, the number of events remained low at 10 years. In all groups, 10-year rates of LRR were relatively low compared with historical studies. As such, the use of PMRT in women with 1 to 3 positive nodes should be tailored to individual patient risks. [ABSTRACT FROM AUTHOR]

Purpose: To determine, using the National Cancer Database (NCDB), the impact of the surgery to radiation therapy interval (SRI) on survival in contemporary patients with Wilms tumor (WT).Methods and Materials: The NCDB was queried for patients aged ≤25 years diagnosed from 2004 to 2013 with unilateral WT who underwent definitive surgery and radiation therapy. The SRI was calculated for each patient. A stratified analysis was performed based on presence of metastasis using logistic regression to calculate risk factors for prolonged SRI, with a focus on the recommended SRI according to recent Children's Oncology Group trials (by day 14) and National Wilms Tumor Study-5 (by day 9). Cox regression was performed to assess the association of SRI with overall survival.Results: A total of 1488 patients were included; 32.1% had metastasis at diagnosis. Among both metastatic and nonmetastatic groups, older patients were more likely to have prolonged SRI. For those without metastasis, SRI > 14 days was associated with increased risk of mortality (hazard ratio 2.13, P = .013). Analyzing SRI as a continuous variable also demonstrated an increased risk of death with longer SRI (hazard ratio 1.04 per day, P = .006) in this group. In contrast, among patients with metastasis, no significant association between SRI and mortality was found.Conclusion: Early initiation of radiation therapy remains a critical component of multimodal treatment for patients with nonmetastatic WT. For nonmetastatic patients, SRI ≤ 14 days correlates with improved overall survival. However, no such association was noted for patients with metastases. These results may inform the development of future WT trials. [ABSTRACT FROM AUTHOR]

Purpose: To study correlations between dose-volume parameters of the whole bladder and bladder trigone and late urinary toxicity in locally advanced cervical cancer patients treated with pulsed-dose-rate brachytherapy.Methods and Materials: Patients with locally advanced cervical cancer treated with chemoradiation therapy and pulsed-dose-rate brachytherapy from 2004 to 2015 were included. Cumulative dose-volume parameters of the whole bladder and bladder trigone were converted into 2-Gy/fraction equivalents (EQD2, with α/β = 3 Gy); these parameters, as well as clinical factors, were analyzed as predictors of toxicity in patients without local relapse.Results: A total of 297 patients fulfilled the inclusion criteria. The median follow-up period was 4.9 years (95% confidence interval 4.5-5.3 years). In patients without local relapse (n = 251), the Kaplan-Meier estimated grade 2 or higher urinary toxicity rates at 3 years and 5 years were 25.4% and 32.1%, respectively. Minimal dose to the most exposed 2 cm3 of the whole bladder [Formula: see text] , bladder International Commission on Radiation Units & Measurements (ICRU) (BICRU) dose, and trigone dose-volume parameters correlated with grade 2 or higher toxicity. At 3 years, the cumulative incidence of grade 2 or higher complications was 22.8% (standard error, 2.9%) for bladder [Formula: see text]  < 80 GyEQD2 versus 61.8% (standard error, 12.7%) for [Formula: see text]  ≥ 80 GyEQD2 (P = .001). In the subgroup of patients with bladder [Formula: see text]  ≤ 80 GyEQD2, a trigone dose delivered to 50% of the volume (D50%) > 60 GyEQD2 was significant for grade 2 or higher toxicity (P = .027). The probability of grade 3 or higher toxicities increased with bladder [Formula: see text]  > 80 GyEQD2 (16.7% vs 1.6%; hazard ratio [HR], 5.77; P = .039), BICRU dose > 65 GyEQD2 (4.9% vs 1.3%; HR, 6.36; P = .018), and trigone D50% > 60 GyEQD2 (3.1% vs 1.2%; HR, 6.29; P = .028). Pearson correlation coefficients showed a moderate correlation between bladder [Formula: see text] , BICRU dose, and bladder trigone D50% (P < .0001).Conclusions: These data suggest that [Formula: see text]  ≤ 80 GyEQD2 should be advised for minimizing the risk of severe urinary complications (<15%). Bladder trigone dose was also predictive of severe late urinary toxicity. These constraints need further confirmation in a multicenter prospective setting. [ABSTRACT FROM AUTHOR]

Purpose: Potential dosimetric and clinicopathologic predictors of radiation-induced brain edema after single-fraction or multifraction stereotactic radiosurgery (SRS) for non-base of skull (non-BOS) meningiomas are summarized based on a systematic review of the published literature.Methods and Materials: Reviewed studies (PubMed indexed from 1998 through 2017) included all or some non-BOS meningioma patients, reported risks of edema after SRS, and correlated dosimetric and/or nondosimetric measures with the magnitude of risk.Results: Twenty-six studies reporting risks of edema after SRS for meningioma are reviewed. The treatment techniques as well as distribution of tumor locations, target dosing, and target volume varied across studies. Among 13 studies that included only non-BOS tumors or separately grouped non-BOS tumors, symptomatic edema occurred in 5% to 43% of patients and any edema occurred in 28% to 50%. The reported average time to onset of edema ranged from approximately 3 to 9 months in most studies. Factors reported to significantly correlate with increased risks of edema and/or symptomatic edema after SRS for meningioma include the following: greater tumor margin and/or maximum dose, greater tumor size and/or volume, non-BOS (particularly parasagittal) location, no prior resection for meningioma, and presence of pretreatment edema. Nevertheless, the extent and significance of these factors were inconsistent across studies. Potentially important dosimetric factors, such as volume of brain or tissue receiving single-fraction doses > 10 to 12 Gy, are not well studied.Conclusions: The variability in risks of edema and in factors impacting those risks is likely a result of differences across studies in the clinicopathologic characteristics of the patient populations, as well as differences in treatment modalities and SRS planning and delivery parameters. More studies on pooled populations, grouped by potential prognostic factors such as tumor location and prior therapy, are needed to better understand dosimetric and nondosimetric factors predictive of edema risk after SRS for meningioma. [ABSTRACT FROM AUTHOR]

Purpose Definitive therapy for prostate cancer (eg surgery or radiotherapy) often has side effects, including urinary, sexual and bowel dysfunction. The purpose of this study was to test whether urinary, sexual and bowel functions contribute to emotional distress during the first 2 years after treatment and whether distress may in turn decrease function. Materials and Methods The study participants were 1,148 men diagnosed with clinically localized disease who were treated with surgery (63%) or radiotherapy (37%). Urinary, sexual and bowel functions were assessed with EPIC (Expanded Prostate Cancer Index Composite). Emotional distress was assessed with the NCCN ® (National Comprehensive Cancer Network®) Distress Thermometer. Assessment time points were before treatment, and 6 weeks, and 6, 12, 18 and 24 months after treatment. We used time lagged multilevel models to test whether physical function predicted emotional distress and vice versa. Results Men with worse urinary, bowel and sexual functions reported more emotional distress than others at subsequent time points. The relationships were bidirectional. Men who reported worse distress also reported worse urinary, bowel and sexual functions at subsequent time points. Conclusions Clinicians supported by practice and payer policies should screen for and facilitate the treatment of side effects and heightened emotional distress to improve well-being in survivors of prostate cancer. These interventions may be cost-effective, given that emotional distress can negatively impact functioning across life domains. [ABSTRACT FROM AUTHOR]

Purpose To build multivariate models to assess correctly and efficiently the contribution of tumor characteristics on the rate of regression of choroidal melanomas after brachytherapy in a way that adjusts for confounding and takes into account variation in tumor regression patterns. Design Modeling of longitudinal observational data. Participants Ultrasound images from 330 of 388 consecutive choroidal melanomas (87%) irradiated from 2000 through 2008 at the Helsinki University Hospital, Helsinki, Finland, a national referral center. Methods Images were obtained with a 10-MHz B-scan during 3 years of follow-up. Change in tumor thickness and cross-sectional area were modeled using a polynomial growth-curve function in a nested mixed linear regression model considering regression pattern and tumor levels. Initial tumor dimensions, tumor–node–metastasis (TNM) stage, shape, ciliary body involvement, pigmentation, isotope, plaque size, detached muscles, and radiation parameters were considered as covariates. Main Outcome Measures Covariates that independently predict tumor regression. Results Initial tumor thickness, largest basal diameter, ciliary body involvement, TNM stage, tumor shape group, break in Bruch's membrane, having muscles detached, and radiation dose to tumor base predicted faster regression, whether considering all tumors or those that regressed in a pattern compatible with exponential decay. Dark brown pigmentation was associated with slower regression. In multivariate modeling, initial tumor thickness remained the predominant and robust predictor of tumor regression ( P < 0.0001). In addition, use of ruthenium isotope as opposed to iodine isotope ( P = 0.018) independently contributed to faster regression of tumor thickness. For both isotopes considered alone, initial tumor thickness was the sole clinical predictor of regression ( P < 0.0001). Conclusions Regression of choroidal melanoma after brachytherapy was associated with several clinical tumor and treatment parameters, most of which were shown to reflect initial tumor size. An independent predictor of regression of tumor thickness was the isotope used. These 2 covariates need to be adjusted for when exploring the associations with the rate of regression of histopathologic or genetic features of the tumor. Our model allows such future analyses efficiently without matching. [ABSTRACT FROM AUTHOR]

Background and purpose To determine the safety and tolerability of dose-escalation using modestly accelerated IMRT in high-risk locally advanced thyroid cancer requiring post-operative radiotherapy, and to report preliminary data on efficacy. Materials and methods A sequential Phase I dose-escalation design was used. Dose level one ( DL1 ) received 58.8  Gy /2 8F to the post-operative bed and 50 Gy/28F to elective nodes. DL2 received 66.6 Gy/30F to the thyroid bed, 60 Gy/30F to post-operative nodal levels and 54 Gy/30F to elective nodal levels . Acute (NCICTCv.2.0) and late toxicities (RTOG and modified LENTSOM) were recorded. The primary endpoint was the number of patients with ≥Grade 3 (G3) toxicity at 12 months post-treatment. Results Fifteen patients were recruited to DL1 and twenty-nine to DL2. At 12 months ≥G3 toxicities were 8.3% in both DL1 and DL2. At 60 months, ≥G3 toxicity was reported in 3 (33%) patients in DL1 and 1 (7%) in DL2. One patient in DL2 died at 24 months from radiation-induced toxicity. Time to relapse and overall survival rates were higher in DL2, but this was not statistically significant. Dose-escalation using this accelerated regimen can be safely performed with a toxicity profile similar to reported series using conventional doses. [ABSTRACT FROM AUTHOR]

Background and purpose Purpose of this study was to quantify the OAR dose for different position correction strategies, and to determine which strategy is most optimal for treating patients on the prostate and pelvic lymph nodes. Materials and methods For 30 patients, four different treatment plans were made reflecting different correction strategies: online correction on bony anatomy; offline correction on bony anatomy; online correction on the prostate fiducials; using 1 cm margins around both CTVs. The dose to the PTVs and OARs was quantified and a pairwise statistical analysis was performed. Results No statistically significant differences were observed in the dose to the PTVs, ensuring that any OAR sparing is not caused by differences in PTV coverage. Dose to the rectum and anal canal was lowest when applying an online correction on prostate fiducials, although the total PTV volume was higher. Dose to the small bowel bag and femoral heads was slightly higher compared to online correction on bony structures, but well within clinically acceptable limits. Conclusion Although the total PTV volume is higher when applying an online correction on the prostate, this strategy leads to the most optimal sparing of relevant OARs, at the cost of a slightly higher dose to the femoral heads and small bowel bag. [ABSTRACT FROM AUTHOR]

With increasing numbers of childhood cancer survivors who were treated with radiation, there is a need to evaluate potential biomarkers that could signal an increased risk of developing thyroid cancer. We aimed to examine the relationships between thyrotropin and thyroglobulin levels and the risk of developing thyroid nodules and cancer in a cohort of radiation-exposed children. 764 subjects who were irradiated in the neck area as children were examined and followed for up to 25 years. All subjects underwent a clinical examination, measurements of thyrotropin, thyroglobulin levels and thyroid imaging. At baseline, 216 subjects had thyroid nodules and 548 did not. Of those with nodules, 176 underwent surgery with 55 confirmed thyroid cancers. During the follow-up, 147 subjects developed thyroid nodules including 22 with thyroid cancer. Thyroglobulin levels were higher in subjects with prevalent thyroid nodules (26.1 ng/mL vs 9.37 ng/mL; P < 0.001) and in those who had an initial normal examination but later developed thyroid nodules (11.2 ng/mL vs 8.87 ng/mL; P = 0.017). There was no relationship between baseline thyrotropin levels and the prevalent presence or absence of thyroid nodules, whether a prevalent neoplasm was benign or malignant, subsequent development of thyroid nodules during follow-up or whether an incident nodule was benign or malignant. In conclusion, in radiation-exposed children, higher thyroglobulin levels indicated an increased risk of developing thyroid nodules but did not differentiate between benign and malignant neoplasms. There was no association between the baseline TSH level and the risk of developing thyroid nodules or cancer. [ABSTRACT FROM AUTHOR]

Context: The side effects of radiotherapy (RT) and the occurrence of comorbidity often result in appetite loss in patients, which leads to serious nutritional problems, significantly affecting the patients' treatment results and disease prognosis.Objectives: We aimed to investigate changes in the body composition of patients with cancer from the time they received RT to three months after completion of RT.Methods: A total of 101 cancer patients who received RT, which included head or neck cancer, chest or breast cancer, and abdominal or pelvic cancer patients, were recruited. A longitudinal study design was adopted, in which the body composition analyzer In Body3.0 was used to obtain patient data at six different time points. The data were analyzed through generalized estimating equation.Results: All patients with cancer had the lowest body mass index at the end of RT. For head or neck cancer patients, their total body water and muscle mass decreased significantly in the fourth week of RT and at the end of RT. For chest or breast cancer patients, their body fat mass changed significantly in the second and fourth weeks of RT (β = -0.57, P = 0.0233; β = -3.23, P = 0.0254). For abdominal or pelvic cancer patients, their total body weight and muscle mass decreased significantly in the second week of RT and at the end of RT (β = -1.07, P = 0.0248; β = -5.13, P = 0.0017; β = -1.37, P = 0.0245; β = -6.50, P = 0.0016); their body fat mass increased significantly in the third month after RT (β = 4.61, P = 0.0072).Conclusion: Body composition analysis can be used to promptly and effectively monitor changes in the nutritional status of patients with cancer during the cancer treatment period; changes in the body composition at different repetitions differ between patients with dissimilar cancers. [ABSTRACT FROM AUTHOR]

Radiation-induced fibrosis (RIF) is a major side effect of radiotherapy in cancer patients with no effective therapeutic options. RIF involves excess deposition and aberrant remodeling of the extracellular matrix (ECM) leading to stiffness in tissues and organ failure. Development of preclinical models of RIF is crucial to elucidate the molecular mechanisms regulating fibrosis and to develop therapeutic approaches. In addition to radiation, the main molecular perpetrators of fibrotic reactions are cytokines, including transforming growth factor-β (TGF-β). We hypothesized that human oral fibroblasts would develop an in vitro fibrotic reaction in response to radiation and TGF-β. We demonstrate here that fibroblasts exposed to radiation followed by TGF-β exhibit a fibrotic phenotype with increased collagen deposition, cell proliferation, migration and invasion. In this in vitro model of RIF (RIFiv), the early biological processes involved in fibrosis are demonstrated, along with increased levels of several molecules including collagen 1α1, collagen XIα1, integrin-α2 and cyclin D1 mRNA in irradiated cells. A clinically relevant antifibrotic agent, pentoxifylline, and a curcumin analogue both mitigated collagen deposition in irradiated fibroblast cultures. In summary, we have established an in vitro model for RIF that facilitates the elucidation of molecular mechanisms in radiation-induced fibrosis and the development of effective therapeutic approaches. [ABSTRACT FROM AUTHOR]