Radiotherapy For Malignancies Research Articles

3D printed integrated bolus/headrest for radiation therapy for malignancies involving the posterior scalp and neck

BackgroundMalignancies of the head and neck region, encompassing cutaneous, mucosal, and sarcomatous histologies, are complex entities to manage, comprising of coordination between surgery, radiation therapy, and systemic therapy. Malignancies of the posterior scalp are particular challenging to treat with radiation therapy, given its irregular contours and anatomy as well as the superficial location of the target volume. Bolus material is commonly used in radiation therapy to ensure that the dose to the skin and subcutaneous tissue is appropriate and adequate, accounting for the buildup effect of megavoltage photon treatment. The use of commercially available bolus material on the posterior scalp potentially creates air gaps between the bolus and posterior scalp.Case presentationsIn this report, we created and utilized a custom 3D-printed integrated bolus and headrest for 5 patients to irradiate malignancies involving the posterior scalp, including those with cutaneous squamous cell carcinoma, melanoma, malignant peripheral nerve sheath tumor, and dermal sarcoma. Treatment setup was consistently reproducible, and patients tolerated treatment well without any unexpected adverse effects.ConclusionsWe found that the use of this custom 3D-printed integrated bolus/headrest allowed for comfortable, consistent, and reproducible treatment set up while minimizing the risk of creating significant air gaps and should be considered in the radiotherapeutic management of patients with posterior scalp malignancies.

Progressing radiation injury of the rectum. Clinical observation

Radiation damage to the rectum is the most common complication in radiation therapy of malignancies of pelvic organs. Clinical manifestations of chronic radiation proctitis can occur both 3 months after completion of therapy and decades later. Late radiation injuries to the intestine often has a persistent course, drug treatment is prolonged and repeated, in severe cases surgical treatment is required. The article presents literature data on pathophysiology, clinical picture, diagnostics and possibilities of treating this pathology. A clinical case reflecting the progressive course of the disease is described.

Pelvic floor reconstruction after total exenteration for radiation injuries of the pelvic organs (clinical case)

The objective is to present the clinical case of pelvic floor reconstruction after total exenteration.Clinical case. The formation of the combined fistula after surgical treatment and combined radiation therapy for uterine body cancer is presented in female patient (57 years old). The rectum and bladder were removed, the perineal tissue was excised and a vulvectomy was performed. The rectus abdominis muscle was mobilized with epigastric artery and moved to the perineum. The wound was healed by primary tension. The patient lives a full life, adapted, and does not require analgesic therapy.Conclusion. The treatment and diagnosis tactics for regional combined fistulas are not standardized, and surgical treatment is the method of choice, especially in cases where the patient has already had radiation therapy for malignancy and relapse.

Osseointegrated implant supported prostheses in the rehabilitation of severe orbital deformity in 6 cases

Objective: To assess the effectiveness of osseointegrated implant supported prostheses in the rehabilitation of severe orbital deformity. Methods: Retrospective case series. The study collected 6 patients (6 eyes) with severe orbital deformity, who were treated with osseointegrated implant supported prostheses between 2010 and 2016 in Beijing Tongren Eye Center, Beijing Tongren Hospital. Data included demographic characteristics, causes of the deformity, the history of radiotherapy, the site, number and survival of implants, and the ability to wear prostheses. Results: Among the 6 patients, 4 were males, and 2 were females, with a mean age of 27 (16-44) years. The deformity resulted from evisceration or enucleation and radiotherapy for malignancies in 4 patients, from evisceration because of inflammatory pseudotumor in 1 patient, and from enucleation and debridement because of explosion injury and secondary infection in 1 patient. Each patient received 3 implants at the first operation. A total of 18 implants were installed, including 9 placed into the lateral aspect of the supraorbital rim, 6 into the lateral aspect of the infraorbital rim, 1 into the medial aspect of the supraorbital rim, and 2 into the medial aspect of the infraorbital rim. One superior lateral implant failed half a year after implantation, and an additional implant was implanted into the medial aspect of the inferior medial orbital rim for prostheses retention. All the patients were followed up for more than 2 years. No other failures were observed. The soft tissue reaction was acceptable in all patients. All of them were able to wear prostheses with satisfying appearance. Conclusions: Osseointegrated implants provid excellent retention for orbital prostheses. This technique could be used in patients with severe orbital deformity to improve their life quality. (Chin J Ophthalmol, 2019, 55: 665-669).

New generation implantable cardiac rhythm devices allow safe radiotherapy treatments: A large single centre study

INTRODUCTION: Many patients requiring radiotherapy for malignancies have an already implanted cardiac rhythm device. Previous studies reported a variety of device dysfunctions related to high dose radiation. Aim of this study was to assess the impact of current optimal radiotherapy treatment guided by computed tomography on current generation implantable devices. METHODS: Consecutive patients with implanted pacemakers (PMK) and implantable cardioverter defibrillators (ICD) referred for radiotherapy treatment in any district were enrolled at our Centre and followed prospectively with device interrogation before and just after each radiotherapy cycle. A magnet was positioned on the device in patients with implanted defibrillators or pacemaker-dependency. RESULTS: Overall, 48 patients (74.8 years (9.3), 39 males (81.3)) with implantable devices underwent radiotherapy (29 pacemakers and 19 ICDs). Interval between device implant and start of radiation therapy was 2.9 (1.6) years. Radiotherapy was performed under computed tomography guidance, and a mean of 73.5 (45.0) Gy were administered with a mean of 24.8 (14.6) fractionated doses. About half of the patients underwent thoracic radiotherapy, and 9 were treated for a left thoracic malignancy ipsilateral to the implanted device. No device failures were observed at post-treatment device interrogation, nor changes in electrical parameters, inappropriate shocks, device reprogramming or memory reset. None of the patients experienced premature battery failure or other unexpected anomalous findings at the end of the radiation therapy cycle. CONCLUSION: Radiation therapy for malignancies is safe among patients with implanted current generation cardiac rhythm devices.

O1. The perturbation effect of titanium prosthesis on megavoltage radiotherapy beams: Photon versus electron beam measurements in a pelvic prosthesis phantom

Introduction In some clinical situations involving external beam radiotherapy of malignancies in the hip region, patients may have metallic implants that could alter the absorbed dose distribution to the target and to normal tissue in the vicinity of the implant. This study investigates and compares the magnitudes of 10 × 10 cm 2 photon (6 and 15 MV) and electron (18 and 22 MeV) beam dose perturbations caused by unilateral titanium prosthesis. Materials and methods Dose perturbations were measured and compared using dose maps and depth dose curves. Measurements were made with Gafchromic EBT2 films in a pelvic phantom made out of nylon slices. Transmission measurements were acquired in narrow beam geometry to determine the mass attenuation coefficient of nylon = 0.0443 cm 2 /g and for water-equivalent RW3 phantom material it was 0.0465 cm 2 /g. The magnitudes of dose deviation caused by the prosthesis were quantified by dose perturbation factors (DPFs), defined as the ratio of the dose influenced by the prosthesis and the unaltered beam. Results For the 6 and 15 MV photons, maximum dose enhancements of 26.5 ± 1.0% and 29.0 ± 1.3%, and dose reductions of 19.9 ± 1.2% and 17.7 ± 1.1% were observed at the proximal interface and in the distal region of the prosthesis, respectively. For the 18 and 22 MeV electron beams respectively, maximum dose escalations of 17.4 ± 0.6% and 20.2 ± 0.7% were obtained at the proximal interface. A local hot spot of about 10% was however observed in the distal region of the prosthesis for the 22 MeV electrons. For the studied beams, the DPFs on the proximal side of the prosthesis fall off rapidly with distance from the proximal interface. Conclusion The dose enhancement increases with increase in beam energy, with higher magnitudes obtained for the photon energies for the field size studied. The photon dose attenuation decreases with increase in photon energy.

Meningioma after radiotherapy for malignancy

Complications of radiation exposure have gained importance with increasing cancer survivorship. Secondary malignancies have been associated with cranial radiation exposure. We present our experience with intracranial radiation-induced meningioma (RIM) and discuss the implications of its presentation and natural history for patient management. Patients diagnosed with meningioma who had received radiation therapy between 1960 and 2014 were identified. Records were retrospectively reviewed for details of radiation exposure, previous malignancies, meningioma subtypes, multiplicity and pathologic descriptions, treatment and follow-up. Thirty patients were diagnosed with RIM. Initial malignancies included acute lymphocytic leukemia (33.3%), medulloblastoma (26.7%) and glioma (16.7%) at a mean age of 8.1years (range 0.04–33years). The mean radiation dose was 34Gy (range 16–60Gy) and latency time to meningioma was 26years (range 8–51years). Twenty-one patients (70%) underwent surgery. Of these, 57.1% of tumors were World Health Organization (WHO) grade I while 42.9% were WHO II (atypical). The mean MIB-1 labeling index for patients with WHO I tumors was 5.44%, with 33.3% exhibiting at least 5% staining. Mean follow-up after meningioma diagnosis was 5.8years. Mortality was zero during the follow-up period. Meningioma is an important long-term complication of therapeutic radiation. While more aggressive pathology occurs more frequently in RIM than in sporadic meningioma, it remains unclear whether this translates into an effect on survival. Further study should be aimed at delineating the risks and benefits of routine surveillance for the development of secondary neoplasms after radiation therapy.

Effect of high energy X-ray irradiation on the nano-mechanical properties of human enamel and dentine.

Radiotherapy for malignancies in the head and neck can cause common complications that can result in tooth damage that are also known as radiation caries. The aim of this study was to examine damage to the surface topography and calculate changes in friction behavior and the nano-mechanical properties (elastic modulus, nanohardness and friction coefficient) of enamel and dentine from extracted human third molars caused by exposure to radiation. Enamel and dentine samples from 50 human third molars were randomly assigned to four test groups or a control group. The test groups were exposed to high energy X-rays at 2 Gy/day, 5 days/week for 5 days (10 Gy group), 15 days (30 Gy group), 25 days (50 Gy group), 35 days (70 Gy group); the control group was not exposed. The nanohardness, elastic modulus, and friction coefficient were analyzed using a Hysitron Triboindenter. The nano-mechanical properties of both enamel and dentine showed significant dose-response relationships. The nanohardness and elastic modulus were most variable between 30-50 Gy, while the friction coefficient was most variable between 0-10 Gy for dentine and 30-50 Gy for enamel. After exposure to X-rays, the fracture resistance of the teeth clearly decreased (rapidly increasing friction coefficient with increasing doses under the same load), and they were more fragile. These nano-mechanical changes in dental hard tissue may increase the susceptibility to caries. Radiotherapy caused nano-mechanical changes in dentine and enamel that were dose related. The key doses were 30-50 Gy and the key time points occurred during the 15th-25th days of treatment, which is when application of measures to prevent radiation caries should be considered.

Current treatments and preventive strategies for radiation retinopathy.

Radiation retinopathy remains a devastating cause of visual morbidity in patients undergoing radiation for globe, orbit, and head and neck malignancies. This review discusses the recent efforts of several authors to treat radiation retinopathy once it has developed and efforts to prevent its development with early aggressive management. Intravitreal anti-vascular endothelial growth factor agents and intravitreal steroid agents have been used to successfully treat radiation-induced macular edema and neovascular events secondary to radiation retinopathy. The visual outcomes, however, have varied. Recent work has been directed towards prevention of radiation retinopathy prior to its development. This has been done with preventive scatter laser and intravitreal bevacizumab therapy. Effective customization of radiation dose to the tumor has also reduced some collateral radiation damage. Preventive vitrectomy and silicone oil placement at the time of plaque brachytherapy may shield normal ocular structures from radiation injury. Radiation retinopathy remains a major source of visual morbidity following radiotherapy for malignancies. Promising, albeit unproven, new therapies and preventive efforts may ameliorate the negative visual outcomes.

18F-FDG PET-CT in the Management of Patients Receiving Definitive Radiotherapy for Malignancies of the Head and Neck

The study investigated the utility and timing of 18F-FDG PET-CT to evaluate for residual/recurrent or metastatic HNC in patients treated with definitive intensity modulated radiation therapy (IMRT) with or without chemotherapy, planned with 18F-FDG PET-CT. The incidence and timing of locoregional recurrence, distant metastatic disease, new primary malignancies, and death were evaluated in 261 patients retrospectively. Findings were classified based on pathology or clinical follow-up and the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of FDG PET-CT were determined overall as well as at the time of each 18F-FDG PET-CT. The overall accuracy for 18F-FDG PET in the detection of residual/recurrent malignancy or metastatic disease was 96.4%. Of those in whom cancer recurred locally, 57% were identified based on physical examination and other imaging findings and 43% were identified initially on 18F-FDG PET-CT surveillance imaging when no disease was evident clinically. 18F-FDG PET-CT has a high diagnostic capability of detecting residual/recurrent malignancy or malignant metastatic disease in patients with HNC following IMRT ± concurrent chemotherapy, supporting 18F- FDG PET-CT’s use to evaluate patients for recurrent malignancy in the post-IMRT period, even without clinical evidence of disease.

Management and prognosis of esophageal carcinosarcoma

Management and prognosis of esophageal carcinosarcoma

Esophageal cancer after mediastinal irradiation for malignancies: A case-control study

Esophageal cancer after mediastinal irradiation for malignancies: A case-control study

A primer on wound healing in colorectal surgery in the age of bioprosthetic materials.

Wound healing is a complex, dynamic process that is vital for closure of cutaneous injuries, restoration of abdominal wall integrity after laparotomy closure, and to prevent anastomotic dehiscence after bowel surgery. Derangements in healing have been described in multiple processes including diabetes mellitus, corticosteroid use, irradiation for malignancy, and inflammatory bowel disease. A thorough understanding of the process of healing is necessary for clinical decision making and knowledge of the current state of the science may lead future researchers in developing methods to enable our ability to modulate healing, ultimately improving outcomes. An exciting example of this ability is the use of bioprosthetic materials used for abdominal wall surgery (hernia repair/reconstruction). These bioprosthetic meshes are able to regenerate and remodel from an allograft or xenograft collagen matrix into site-specific tissue; ultimately being degraded and minimizing the risk of long-term complications seen with synthetic materials. The purpose of this article is to review healing as it relates to cutaneous and intestinal trauma and surgery, factors that impact wound healing, and wound healing as it pertains to bioprosthetic materials.

Comparative assessment of the therapeutic effects of the topical and systemic forms of Hypericum perforatum extract on induced oral mucositis in golden hamsters

Oral mucositis is a common and irritating complication of chemotherapy and radiotherapy for malignancies. Current treatments have failed to achieve complete remission of this complication. The St. John's wort plant (Hypericum perforatum) has long been known for its anti-inflammatory and antibacterial effects. The current study was designed to investigate the therapeutic efficacy of the topical and systemic administration of H. perforatum extract on oral mucositis. Oral mucositis was induced in 72 male golden hamsters by administration of 5-fluorouracil (60mg/kg), on days 0, 5, and 10 of the study. The cheek pouch was scratched with a sterile needle on days 1 and 2. On days 12–17, H. perforatum extract topical gel 10%, oral H. perforatum extract (300mg/kg), and gel base groups were treated and then compared with a control group. Weights and blood samples were evaluated, biopsies from buccal lesions were examined histopathologically, and tissue malondialdehyde (MDA) was measured. Both of the H. perforatum extract treatment groups saw a significant relief in oral mucositis compared to the control and base gel groups; the systemic form was superior to the topical form. H. perforatum extract, administered orally or topically, expedited the healing of chemotherapy-induced oral mucositis in hamsters.

Transforming growth factor-β1/Smad/connective tissue growth factor axis: The main pathway in radiation-induced fibrosis of osteoradionecrosis?

Introduction: Osteoradionecrosis (ORN) of the mandible is a serious complication following radiation therapy for malignancies of the head and neck. Radiation-induced fibrosis (RIF) is a new theory that accounts for the damage to normal tissues after radiotherapy, and the radiation-induced fibroatrophic mechanism includes the free-radical formation, endothelial dysfunction, inflammation, microvascular thrombosis, fibrosis and remodeling, and finally bone and tissue necrosis. The Hypothesis: Previous studies revealed that transforming growth factor-β1 (TGF-β1) is the master switch cytokine responsible for the regulation of fibroblast proliferation and differentiation that result in RIF. Among the targets of TGF-β1, connective tissue growth factor (CTGF) is a downstream mediator through the Smad3/4 pathway and plays an important role in connective tissue homeostasis and fibroblast proliferation. Studies have proved that the TGF-β1/Smad/CTGF signaling pathway is involved in the RIF of soft tissues, so the authors put forward a hypothesis that the TGF-β1/Smad/CTGF axis is also the main pathway in RIF of ORN. Evaluation of the Hypothesis: The validation of our hypothesis may provide new insights for better understanding the pathogenesis of ORN and open new perspectives for anti-fibrotic therapies, and pioneer novel approaches to treat ORN.

Do insulin-like growth factor associated proteins qualify as a tumor marker?

18 Background: Insulin-like growth factor (IGF)-1, -2 and insulin-like growth factor binding proteins (IGFBP) are involved in the proliferation and differentiation of cells. It has never been evaluated if the IGF-system can serve as a tumor marker in neoplasms. Methods: In our prospective study, 163 patients with colorectal cancer (22), prostate cancer (21), glioblastoma (12), head and neck tumors (17), lymphomas (20), lung cancer (34), and other entities (37) were analysed for their IGF and IGFBP serum levels at the beginning and the end of radiotherapy and compared with 13 healthy people. Subgroups of patients with local tumor disease versus metastatic disease, primary and recurrent therapy and curative versus palliative therapy were compared. Results: The serum levels of IGF-2 were significantly elevated in patients with prostate and colorectal cancer. However, sensitivity and specificity were only 70%. IGFBP-2 serum levels were elevated in patients with head and neck tumors. Again, sensitivity and specificity were only 73%. A difference between local disease and metastatic disease could not be found. A difference between IGF serum levels before and after radiotherapy could not be detected. Conclusions: The IGF-system cannot serve as a new tumor marker. The detected differences are very small and sensitivity and specificity are too low. IGF measurement is not useful for the evaluation of the success of radiotherapy in malignancies.

Radiation-Induced Gut Damage: Identifying “at Risk” Patients With an “Electronic Nose” (E-Nose)

Introduction Almost all patients undergoing radical pelvic radiotherapy develop bowel symptoms during treatment and half go on to develop chronic bowel symptoms. Acute histological damage, due to the radiation, is at its worst at 2 weeks and then improves; subsequent chronic damage then is sustained over many years. We investigated if changes in gastrointestinal symptoms during radiotherapy correlated with alterations in colonic microbial balance, reflected by changes in the gases released when undigested fibre is fermented. Two hypotheses were investigated in this pilot study: (1) Irradiation alter the microbial flora, reflected by changes in the fermentation profile. (2) An individual9s susceptibility to damage may be recognised by their ‘fermentation signature9. Methods Two groups were selected from patients undergoing pelvic radiotherapy for malignancy: those ‘hardly affected’ and ‘severely affected’. All completed a validated Inflammatory Bowel Disease Questionnaire Bowel subset score (IBDQ-B) which was recorded before irradiation and at 4 weeks. Scores : 10–70; 70=‘normal’ (no symptoms). Faecal samples were collected at these times and immediately frozen at −20°C until analysis. Faecal samples were heated to 38 ± 0.1°C and the headspace (the air above the sample) analysed using a modified FOX 2000 series E-nose. This uses an array of 14 chemical sensors which are either broadly tuned to a chemical groups or to specific gases. Data analysis was by: (1) Principal Component Analysis (PCA): all data are analysed together without prior categorisation, and results displayed as clusters of individuals with shared features. (2) Linear Discriminant Analysis (LDA): samples are pre-categorised (clinical groups) and the system searches for additional features to enhance categorisation. Results Mean IBDQ-B score (± SD). All patients before radiotherapy had little or no symptoms but LDA showed 2 clusters with only slight overlap. One group developed severe symptoms, reflected by the fall in IBDQ-B scores. The corresponding PCA showed 2 distinct clusters without overlap. LDA: Almost all who became ‘severely affected’ arose from its corresponding baseline cluster. Conclusion This pilot study supports our hypothesis: (1) The fermentation signature tracks changes induced by pelvic irradiation. (2) It suggests those ‘at risk’ of severe radiation-induced gut damage may be identifiable before treatment.

Leucémies aiguës myéloïdes secondaires aux traitements : implication des mécanismes de réparation de l'ADN

The survival improvement of patients treated with chemotherapy or radiotherapy for malignancies are increasing therapy-related acute myeloid leukemia (t-AML). It was thought to be the direct consequence of genetic events induced by such treatments. We here review the mechanisms of specific chemotherapy-related DNA damage inducing the chromosomal or genomic abnormalities characteristic of t-AML. We also focus on how such aberrations could initiate or participate to leukemogenesis. However, only a part of patients exposed to cytotoxic therapy is developing t-AML, suggesting that some genetic predisposition may be involved such as polymorphisms in genes related to DNA repair.

Do insulin-like growth factor associated proteins qualify as a tumor marker? results of a prospective study in 163 cancer patients*

ObjectiveInsulin-like growth factor (IGF)-1, -2 and Insulin like growth factor binding proteins (IGFBP) are involved in the proliferation and differentiation of cells. It has never been evaluated, if the IGF-system can serve as a tumor marker in neoplasms.MethodsIn our prospective study 163 patients with colorectal cancer (22), prostate cancer (21), head and neck tumors (17), lymphomas (20), lung cancer (34) and other entities (49) were analysed for their IGF and IGFBP serum levels at the beginning and the end of radiotherapy and compared to 13 healthy people. Subgroups of patients with local tumor disease versus metastatic disease, primary and recurrent therapy and curative versus palliative therapy were compared.ResultsThe serum levels of IGF-2 were significantly elevated in patients with prostate and colorectal cancer. However, sensitivity and specificity were only 70%. IGFBP-2 serum levels were elevated in patients with head and neck tumors. Again sensitivity and specificity were only 73%. A difference between local disease and metastatic disease could not be found. A difference between IGF serum levels before and after radiotherapy could not be detected.ConclusionThe IGF-system cannot serve as a new tumor marker. The detected differences are very small, sensitivity and specificity are too low. IGF measurement is not useful for the evaluation of the success of radiotherapy in malignancies.

Vesico-vaginal fistula post cold cup bladder biopsy: mini review

IntroductionWe report a case of a vesico-vaginal fistula (VVF) post cold cup biopsy; to our knowledge this is the only reported case. We present the clinical history/presentation, investigation and the outcome of the treatment. VVFs are among the most distressing complications of gynecologic and obstetric procedures. The risk of developing a VVF is more than 1% after radical surgery and radiotherapy for malignancies. Management of these fistulas has been better defined and standardized over the last decade.Methods and resultsA case of low grade superficial bladder cancer was treated with multiple resections of bladder tumor and a single installation of mitomycin post initial resection which successfully cleared her bladder cancer, but nevertheless led to a small size and scarred bladder. In addition there was a long history of smoking with its effects on tissue integrity and healing. VVFs are very rare and are an unpleasant outcome post a cold cup biopsy, adding to the psychological and social effects of the surgical treatment.ConclusionAlthough cold cup biopsy is a normal day procedure performed by both residents and consultants, consensus should exist on how to treat a patient who has a bladder with defective integrity and small capacity. The rate of successful fistula repair reported in the literature varies between 70% and 100% in nonradiated patients, with similar results when a vaginal or abdominal approach is performed, the mean success rates being 91% and 97%, respectively.