Riesgo de osteorradionecrosis de los maxilares según el tipo de radioterapia / Risk of Osteoradionecrosis of the Jaws according to Type of Radiotherapy

Introducción: El cáncer de cabeza y cuello es el séptimo más común a nivel mundial. Las opciones terapéuticas para su manejo incluyen la radioterapia, la cual debe procurar un equilibrio entre la eliminación del tumor y la preservación del tejido sano porque su aplicación implica el riesgo de desarrollar una osteorradionecrosis de los maxilares. Objetivo: Valorar si el riesgo de que se produzca osteorradionecrosis de los maxilares varía en función del tipo de radioterapia. Métodos: Diseño documental, retrospectivo basado en los principios de las revisiones sistemáticas exploratorias según lo establece la lista de chequeo PRISMA Extension for Scoping Reviews (PRISMA-ScR). Se realizaron búsquedas en inglés y español en PubMed, LILACS, ScienceDirect, Tripdatabase y Epistemonikos. Resultados: En total se incluyeron 12 estudios publicados entre 2016 y 2022 con diversos diseños de investigación; el estudio de cohorte retrospectivo fue el que tuvo mayor representación. Se analizaron distintas opciones de radioterapia y sus protocolos, entre ellos, la radioterapia de intensidad modulada, la terapia de protones de intensidad modulada, la radioterapia corporal estereotáctica y la radioterapia tridimensional. La literatura refiere que los protocolos que implican dosis totales más bajas representan un menor riesgo de osteorradionecrosis. Conclusiones: El riesgo de osteorradionecrosis de los maxilares debe atribuirse, en mayor medida, a la dosis total de radiación recibida por el paciente y a la dosis por fracción que al tipo de radioterapia(AU)

Introduction: Head and neck cancer is the seventh most common cancer worldwide. Therapeutic options for its management include radiotherapy, which should seek a balance between tumor elimination and preservation of healthy tissue because its application implies the risk of developing osteoradionecrosis of the jaws. Objective: To assess whether the risk of developing osteoradionecrosis of the jaws varies according to the type of radiotherapy. Methods : Documentary, retrospective design based on the principles of exploratory systematic reviews as established by the PRISMA Extension for Scoping Reviews (PRISMA-ScR) checklist. PubMed, LILACS, ScienceDirect, Tripdatabase and Epistemonikos were searched in English and Spanish. Results: In total, 12 studies published between 2016 and 2022 with various research designs were included; the retrospective cohort study had the highest representation. Different radiotherapy options and their protocols were analyzed, including intensity-modulated radiotherapy, intensity-modulated proton therapy, stereotactic body radiotherapy, and three-dimensional radiotherapy. The literature refers that protocols involving lower total doses represent a lower risk of osteoradionecrosis. Conclusions: The risk of osteoradionecrosis of the jaws should be attributed, to a greater extent, to the total radiation dose received by the patient and the dose per fraction than to the type of radiotherapy(AU)

Monte Carlo simulations of cell survival in proton SOBP.

Objective. The objective of this study is to develop a multi-scale modeling approach that accurately predicts radiation-induced DNA damage and survival fraction in specific cell lines.Approach. A Monte Carlo based simulation framework was employed to make the predictions. The FLUKA Monte Carlo code was utilized to estimate absorbed doses and fluence energy spectra, which were then used in the Monte Carlo Damage Simulation code to compute DNA damage yields in Chinese hamster V79 cell lines. The outputs were converted into cell survival fractions using a previously published theoretical model. To reduce the uncertainties of the predictions, new values for the parameters of the theoretical model were computed, expanding the database of experimental points considered in the previous estimation. Simulated results were validated against experimental data, confirming the applicability of the framework for proton beams up to 230 MeV. Additionally, the impact of secondary particles on cell survival was estimated.Main results. The simulated survival fraction versus depth in a glycerol phantom is reported for eighteen different configurations. Two proton spread out Bragg peaks at several doses were simulated and compared with experimental data. In all cases, the simulations follow the experimental trends, demonstrating the accuracy of the predictions up to 230 MeV.Significance. This study holds significant importance as it contributes to the advancement of models for predicting biological responses to radiation, ultimately contributing to more effective cancer treatment in proton therapy.

Hospital-based proton therapy implementation during the COVID pandemic: early clinical and research experience in a European academic institution.

INTRODUCTION: A rapid deploy of unexpected early impact of the COVID pandemic in Spain was described in 2020. Oncology practice was revised to facilitate decision-making regarding multimodal therapy for prevalent cancer types amenable to multidisciplinary treatment in which the radiotherapy component searched more efficient options in the setting of the COVID-19 pandemic, minimizing the risks to patients whilst aiming to guarantee cancer outcomes. METHODS: A novel Proton Beam Therapy (PBT), Unit activity was analyzed in the period of March 2020 to March 2021. Institutional urgent, strict and mandatory clinical care standards for early diagnosis and treatment of COVID-19 infection were stablished in the hospital following national health-authorities' recommendations. The temporary trends of patients care and research projects proposals were registered. RESULTS: 3 out of 14 members of the professional staff involved in the PBR intra-hospital process had a positive test for COVID infection. Also, 4 out of 100 patients had positive tests before initiating PBT, and 7 out of 100 developed positive tests along the weekly mandatory special checkup performed during PBT to all patients. An update of clinical performance at the PBT Unit at CUN Madrid in the initial 500 patients treated with PBT in the period from March 2020 to November 2022 registers a distribution of 131 (26%) pediatric patients, 63 (12%) head and neck cancer and central nervous system neoplasms and 123 (24%) re-irradiation indications. In November 2022, the activity reached a plateau in terms of patients under treatment and the impact of COVID pandemic became sporadic and controlled by minor medical actions. At present, the clinical data are consistent with an academic practice prospectively (NCT05151952). Research projects and scientific production was adapted to the pandemic evolution and its influence upon professional time availability. Seven research projects based in public funding were activated in this period and preliminary data on molecular imaging guided proton therapy in brain tumors and post-irradiation patterns of blood biomarkers are reported. CONCLUSIONS: Hospital-based PBT in European academic institutions was impacted by COVID-19 pandemic, although clinical and research activities were developed and sustained. In the post-pandemic era, the benefits of online learning will shape the future of proton therapy education.

CONVERSION OF DOSE DISTRIBUTION TO CELL SURVIVAL FRACTION THROUGH DNA DAMAGE: A MONTE CARLO STUDY.

Ionizing radiation plays an important role in cancer treatment. Radiation is able to damage the genetic material of cells, blocking their ability to divide and proliferate further. Since radiation affects both healthy and malignant tissues, for all radiation treatments, the design of an accurate treatment plan is fundamental. Usually, weight factors, such as the relative biological effectiveness, are applied to estimate the impact of the kind of radiation and the irradiated medium on the dose deposition. However, these factors can only provide a partial estimation of the real effect on tissues. In this work, a flexible system that is able to predict cell survival fractions according to the planned dose distribution is presented. Dose deposition and subsequent DNA damage were simulated with a multi-scale modeling approach by first applying the FLUKA Monte Carlo (MC) code to estimate the absorbed doses and fluence energy spectra and then using the MC Damage Simulation code to compute the DNA damage yields. Lastly, the results are converted into cell survival fraction using a theoretical model. The comparisons between the simulated survival fractions with experimental data are reported for a proton spread out Bragg peak at several doses. The presented approach helps to elucidate radiobiological responses along the Bragg curve and has the flexibility to be extended to a wide range of situations of clinical interest.

The role of proton therapy in pediatric malignancies: Recent advances and future directions.

Proton radiotherapy has promised an advantage in safely treating pediatric malignancies with an increased capability to spare normal tissues, reducing the risk of both acute and late toxicity. The past decade has seen the proliferation of more than 30 proton facilities in the United States, with increased capacity to provide access to approximately 3,000 children per year who will require radiotherapy for their disease. We provide a review of the initial efforts to describe outcomes after proton therapy across the common pediatric disease sites. We discuss the main attempts to assess comparative efficacy between proton and photon radiotherapy concerning toxicity. We also discuss recent efforts of multi-institutional registries aimed at accelerating research to better define the optimal treatment paradigm for children requiring radiotherapy for cure.

Radiotherapy in soft-tissue sarcoma of the extremities.

Sarcomas are an infrequent and heterogeneous group of neoplasia. Surgery with or without associated radiotherapy (RT) is the basic treatment for this type of tumour. To increase the therapeutic ratio (the index between cytotoxic effects in tumours and normal tissue complications with a certain dose of radiation), new advances are being investigated to increase local and distant control and to decrease the morbidity of the treatment. The aim of this review was to analyse the different strategies, based on technology and biology, which are being investigated to increase the therapeutic ratio of this disease.

Patient characterization and usage trends of proton beam therapy for localized prostate cancer in the United States: A study of the National Cancer Database.

PURPOSE: To evaluate usage trends and identify factors associated with proton beam therapy (PBT) compared to alternative forms of external beam radiation therapy (RT) (EBRT) for localized prostate cancer. PATIENTS AND METHODS: The National Cancer Database was queried for men with localized (N0, M0) prostate cancer diagnosed between 2004 and 2013, treated with EBRT, with available data on EBRT modality (photon vs. PBT). Binary multiple logistic regression identified variables associated with EBRT modality. RESULTS: In total, 143,702 patients were evaluated with relatively few men receiving PBT (5,709 [4.0%]). Significant differences in patient and clinical characteristics were identified between those men treated with PBT compared to those treated with photon (odds ratio [OR]; 95% CI). Patients treated with PBT were generally younger (OR = 0.73; CI: 0.67-0.82), National Comprehensive Cancer Network low-risk compared to intermediate (0.71; 0.65-0.78) or high (0.44; 0.38-0.5) risk, white vs. black race (0.66; 0.58-0.77), with less comorbidity (Charlson-Deyo 0 vs. 2+; 0.70; 0.50-0.98), live in higher income counties (1.55; 1.36-1.78), and live in metropolitan areas compared to urban (0.21; 0.18-0.23) or rural (0.14; 0.10-0.19) areas. Most patients treated with PBT travelled more than 100 miles to the treatment facility. Annual PBT utilization significantly increased in both total number and percentage of EBRT over time (2.7%-5.6%; P<0.001). PBT utilization increased mostly in men classified as National Comprehensive Cancer Network low-risk (4%-10.2%). CONCLUSION: PBT for men with localized prostate cancer significantly increased in the United States from 2004 to 2013. Significant demographic and prognostic differences between those men treated with photons and protons were identified.

The management of head and neck tumors with high technology radiation therapy.

Squamous cell carcinoma is responsible for 90% of the head and neck cancers affecting over 600,000 people worldwide. Radiation therapy, surgery and chemotherapy are the most important treatment modalities in head and neck squamous cell carcinoma. The aim of this review is to summarize the recent innovations in head and neck radiation therapy, which intends to appreciate the cutting-edge intensity-modulated radiation therapy strategies to mitigate long-term toxicities and evaluate promising technologies in the field as adaptive treatment, dose painting and proton therapy.

The incidence of second brain tumors related to cranial irradiation.

Secondary brain tumor (SBT) is a devastating complication of cranial irradiation (CI). We reviewed the literature to determine the incidence of SBT as related to specific radiation therapy (RT) treatment modalities. The relative risk of radiation-associated SBT after conventional and conformal RT is well established and ranges from 5.65 to 10.9; latent time to develop second tumor ranges from 5.8 to 22.4 years, depending on radiation dose and primary disease. Theories and dosimetric models suggest that intensity-modulated radiation therapy may result in an increased risk of SBT, but clinical evidence is limited. The incidence of stereotactic radiosurgery-related SBT is low. Initial data suggest that no increased risk from proton therapy and dosimetric models predict a lower incidence of SBT compared with photons. In conclusion, the incidence of SBT related to CI is low. Longer follow-up is needed to clarify the impact of intensity-modulated radiation therapy, proton therapy and other developing technologies.

The use of proton therapy in the treatment of head and neck cancers.

External beam radiation therapy is a commonly utilized treatment modality in the management of head and neck cancer. Given the close proximity of disease to critical normal tissues and structures, the delivery of external beam radiation therapy can result in severe acute and late toxicities, even when delivered with advanced photon-based techniques, such as intensity-modulated radiation therapy. The unique physical characteristics of protons make it a promising option in the treatment of advanced head and neck cancer, with the potential to improve sparing of normal tissues and/or safely escalate radiation doses. Clinical implementation will require the continued development of advanced techniques such as intensity-modulated proton therapy, using pencil beam scanning, as well as rigorous methods of quality assurance and adaptive techniques to accurately adjust to changes in anatomy due to disease response. Ultimately, the widespread adaptation and implementation of proton therapy for head and neck cancer will require direct, prospective comparisons to standard techniques such as intensity-modulated radiation therapy, with a focus on measures such as toxicity, disease control, and quality of life.

The use of proton therapy in the treatment of gastrointestinal cancers: liver.

This article reviews the role of proton therapy in the treatment of primary liver cancer focusing on hepatocellular carcinoma (HCC). The dose-sparing physical properties of protons are of great advantage in the treatment of HCC. To date, the clinical experience with the use of protons for HCC is encouraging. Most studies come from East Asia and show improved local control and survival with low toxicity. More importantly, when high-enough radiation doses are delivered to early liver cancers, a substantial fraction of patients are alive at 5 years, results not dissimilar from surgical resection. The technical details related to the use of proton therapy for HCC are also reviewed. The combination of proton therapy with other locoregional or systemic therapies is currently being tested and holds promise to improve survival while maintaining an acceptable level of toxicity.

A comprehensive dosimetric study of pancreatic cancer treatment using three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), volumetric-modulated radiation therapy (VMAT), and passive-scattering and modulated-scanning proton therapy (PT).

With traditional photon therapy to treat large postoperative pancreatic target volume, it often leads to poor tolerance of the therapy delivered and may contribute to interrupted treatment course. This study was performed to evaluate the potential advantage of using passive-scattering (PS) and modulated-scanning (MS) proton therapy (PT) to reduce normal tissue exposure in postoperative pancreatic cancer treatment. A total of 11 patients with postoperative pancreatic cancer who had been previously treated with PS PT in University of Pennsylvania Roberts Proton Therapy Center from 2010 to 2013 were identified. The clinical target volume (CTV) includes the pancreatic tumor bed as well as the adjacent high-risk nodal areas. Internal (iCTV) was generated from 4-dimensional (4D) computed tomography (CT), taking into account target motion from breathing cycle. Three-field and 4-field 3D conformal radiation therapy (3DCRT), 5-field intensity-modulated radiation therapy, 2-arc volumetric-modulated radiation therapy, and 2-field PS and MS PT were created on the patients' average CT. All the plans delivered 50.4Gy to the planning target volume (PTV). Overall, 98% of PTV was covered by 95% of the prescription dose and 99% of iCTV received 98% prescription dose. The results show that all the proton plans offer significant lower doses to the left kidney (mean and V18Gy), stomach (mean and V20Gy), and cord (maximum dose) compared with all the photon plans, except 3-field 3DCRT in cord maximum dose. In addition, MS PT also provides lower doses to the right kidney (mean and V18Gy), liver (mean dose), total bowel (V20Gy and mean dose), and small bowel (V15Gy absolute volume ratio) compared with all the photon plans and PS PT. The dosimetric advantage of PT points to the possibility of treating tumor bed and comprehensive nodal areas while providing a more tolerable treatment course that could be used for dose escalation and combining with radiosensitizing chemotherapy.

Proton therapy and radiation sensitivity in dyskeratosis congenita.

BACKGROUND: Patients with dyskeratosis congenita (DC) have an increased risk of cancer, but also exhibit heightened radiation sensitivity. Proton therapy improves sparing of normal tissue, and thus may reduce radiation toxicity in patients with DC. OBSERVATIONS: We present a pediatric patient with DC who was treated with adjuvant proton therapy for oropharyngeal cancer. He experienced more severe skin toxicity and mucositis than expected. With reduced fractions per week and extensive supportive care, he completed the full radiation course. CONCLUSIONS: Proton therapy can improve normal tissue sparing, allowing successful delivery of radiation therapy in DC patients.

Acute toxicity profile of patients with low-grade gliomas and meningiomas receiving proton therapy.

OBJECTIVES: Proton therapy is an emerging treatment modality. We studied its acute side effects on patients with low-grade gliomas and meningiomas. MATERIALS AND METHODS: Twenty-three patients diagnosed with low-grade gliomas or meningiomas enrolled in an Institutional Review Board-approved prospective proton treatment protocol (NCT01024907) were treated and followed between April 2010 and August 2011. Patients received 54 Gy (relative biological effectiveness) in 1.8 Gy (relative biological effectiveness) per fraction and were assessed at the time of consult, weekly during treatment, and at 1, 3, 6, and 9 months posttreatment. At each clinic visit, nursing completed a "Symptom Assessment/Grading" table. Symptoms were graded based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Fatigue: At on-treatment visit (OTV) week 6, 13 patients had grade 1 and 6 patients had grade 2 fatigue. At 1-month follow-up, 3 patients had grade 1 and 1 patient had grade 2 fatigue. At each timepoint, 1 patient had grade 3 fatigue. Nausea: At OTV week 3, 5 patients experienced grade 1 nausea. At OTV week 6, 3 patients experienced grade 1 nausea. Headache: At OTV week 3, 10 patients had grade 1 headaches. At OTV week 6, 4 patients experienced grade 1 headaches and 1 patient by follow-up month 1. One to 2 patients experienced grade 2 headaches at each timepoint. At OTV week 3, 1 patient experienced a grade 3 headache. CONCLUSIONS: Our results suggest that proton therapy for patients with low-grade gliomas and meningiomas has a favorable acute toxicity profile-most patients experienced mild fatigue, headache, and insomnia that largely resolved by 1-month posttreatment.

The efficacy of hemostatic radiotherapy for bladder cancer-related hematuria in patients unfit for surgery

Objective The aim of our study was to assess short and mid-term clinical efficacy of external beam radiation therapy to achieve hemostasis in patients with bladder-cancer related gross hematuria who were unfit for surgery. We also assessed hypofractionation as a possible alternative option for more severe patients. Patients and Methods Thirty-two patients were included for hemostatic radiation therapy, with two schedules based on Eastern Cooperative Oncology Group performance status. The standard treatment was 30 Gy in 10 fractions over 2 weeks. More severe patients underwent a hypofractionated regimen, with 20 Gy in 5 fractions over a one week period. Clinical evaluation was performed at 2 weeks and 6 months. Results At 2 weeks, 69% of patients were hematuria-free. Subgroup analysis showed that 79% of patients undergoing hypofractionated regimen were hematuria-free. A total of 54% were hematuria-free with the standard regimen. Based on tumor stage, hematuria was controlled at 2 weeks for 57% of non-muscle invasive tumors and 72% of muscle-invasive tumors. After 6 months, 69% of patients had relapsed, regardless of tumor stage or therapy schedules. Conclusions Hemostatic radiotherapy is an effective option for palliative-care hematuria related to bladder cancer in patients unfit for surgery. Although it appears to be rapidly effective, its effect is of limited duration. Hypofractionation also seems to be an effective option; however larger cohorts and prospective trials are needed to evaluate its efficacy compared to standard schedules. .

Geometrical splitting technique to improve the computational efficiency in Monte Carlo calculations for proton therapy.

PURPOSE: To present the implementation and validation of a geometrical based variance reduction technique for the calculation of phase space data for proton therapy dose calculation. METHODS: The treatment heads at the Francis H Burr Proton Therapy Center were modeled with a new Monte Carlo tool (TOPAS based on Geant4). For variance reduction purposes, two particle-splitting planes were implemented. First, the particles were split upstream of the second scatterer or at the second ionization chamber. Then, particles reaching another plane immediately upstream of the field specific aperture were split again. In each case, particles were split by a factor of 8. At the second ionization chamber and at the latter plane, the cylindrical symmetry of the proton beam was exploited to position the split particles at randomly spaced locations rotated around the beam axis. Phase space data in IAEA format were recorded at the treatment head exit and the computational efficiency was calculated. Depth-dose curves and beam profiles were analyzed. Dose distributions were compared for a voxelized water phantom for different treatment fields for both the reference and optimized simulations. In addition, dose in two patients was simulated with and without particle splitting to compare the efficiency and accuracy of the technique. RESULTS: A normalized computational efficiency gain of a factor of 10-20.3 was reached for phase space calculations for the different treatment head options simulated. Depth-dose curves and beam profiles were in reasonable agreement with the simulation done without splitting: within 1% for depth-dose with an average difference of (0.2 ± 0.4)%, 1 standard deviation, and a 0.3% statistical uncertainty of the simulations in the high dose region; 1.6% for planar fluence with an average difference of (0.4 ± 0.5)% and a statistical uncertainty of 0.3% in the high fluence region. The percentage differences between dose distributions in water for simulations done with and without particle splitting were within the accepted clinical tolerance of 2%, with a 0.4% statistical uncertainty. For the two patient geometries considered, head and prostate, the efficiency gain was 20.9 and 14.7, respectively, with the percentages of voxels with gamma indices lower than unity 98.9% and 99.7%, respectively, using 2% and 2 mm criteria. CONCLUSIONS: The authors have implemented an efficient variance reduction technique with significant speed improvements for proton Monte Carlo simulations. The method can be transferred to other codes and other treatment heads.

The efficacy of hemostatic radiotherapy for bladder cancer-related hematuria in patients unfit for surgery.

OBJECTIVE: The aim of our study was to assess short and mid-term clinical efficacy of external beam radiation therapy to achieve hemostasis in patients with bladder-cancer related gross hematuria who were unfit for surgery. We also assessed hypofractionation as a possible alternative option for more severe patients. PATIENTS AND METHODS: Thirty-two patients were included for hemostatic radiation therapy, with two schedules based on Eastern Cooperative Oncology Group performance status. The standard treatment was 30 Gy in 10 fractions over 2 weeks. More severe patients underwent a hypofractionated regimen, with 20 Gy in 5 fractions over a one week period. Clinical evaluation was performed at 2 weeks and 6 months. RESULTS: At 2 weeks, 69% of patients were hematuria-free. Subgroup analysis showed that 79% of patients undergoing hypofractionated regimen were hematuria-free. A total of 54% were hematuria-free with the standard regimen. Based on tumor stage, hematuria was controlled at 2 weeks for 57% of non-muscle invasive tumors and 72% of muscle-invasive tumors. After 6 months, 69% of patients had relapsed, regardless of tumor stage or therapy schedules. CONCLUSIONS: Hemostatic radiotherapy is an effective option for palliative-care hematuria related to bladder cancer in patients unfit for surgery. Although it appears to be rapidly effective, its effect is of limited duration. Hypofractionation also seems to be an effective option; however larger cohorts and prospective trials are needed to evaluate its efficacy compared to standard schedules.

Definitive radiotherapy for unresected adenoid cystic carcinoma of the trachea.

Adenoid cystic carcinoma is a rare malignancy that usually originates in the salivary glands of the head and neck but has rarely been known to originate in the trachea. This histology has a predilection for perineural invasion and a tendency for both local and distant recurrences. While surgical resection is the mainstay of treatment of tracheal adenoid cystic carcinoma, tumor size, location, and patient comorbidities may preclude surgery, and the optimal nonsurgical management remains undefined. In the absence of locoregional lymph node metastases, we recommend highly conformal radiotherapy alone to a dose of 80 Gy. We report on two patients with unresectable disease who were treated with definitive radiotherapy: one using conventional photons and one treated with a combination of photon and proton beams. Both patients were treated to a dose of 80 Gy with acceptable toxicities and objective clinical and radiographic response. The patient treated with conventional photons has no evidence of recurrent disease at 5 years; the patient treated with protons has continued evidence of response without evidence of disease recurrence 11 months after treatment.