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Cervical cancer represents a significant portion of the global cancer burden for women, with low- and middle-income countries carrying the bulk of this burden. Additionally, underserved populations in countries with sufficient resources may have a higher incidence of cervical cancer and poorer outcomes. Concurrent chemoradiotherapy is the standard-of-care treatment for locally advanced cervical cancer, which includes patients with stage IB3 to IVA disease, and it is effective for many patients; however, cervical cancer-related mortality remains high. The critical nature of cervical cancer treatment is underscored by the recent launch of the World Health Organization global initiative to accelerate the elimination of cervical cancer using a triple-intervention strategy of increased vaccination, screening, and treatment. The initiative calls for 90% of all patients diagnosed with cervical cancer to receive the appropriate treatment, but to reach this global goal there are significant barriers related to radiothus vaccines, and radiosensitizing nanoparticles.Appropriate diagnosis and treatment of gynecological cancers in people living with human immunodeficiency virus (HIV) remains a clinical challenge given rapid changes in both HIV and cancer management and a lack of prospective clinical trial data inclusive of the HIV population. A semi-systematic literature review was performed to identify published studies addressing risk factors, screening, treatment efficacy, treatment toxicity, and prognosis for people living with HIV diagnosed with gynecological malignancies, with a focus on radiotherapy and cervical cancer, given the relative paucity of literature on uterine, ovarian, and vulvovaginal cancers in people living with HIV. People living with HIV are more likely to be co-infected with human papilloma virus and more likely to develop human papilloma virus-associated malignancies. People living with HIV are less likely to receive cancer treatment compared with HIV-uninfected cancer patients, even after adjusting for differences in clinical features and sociodegement.A disproportionate burden of gynecologic malignancies occurs in low- and middle-income countries. Radiation therapy is an integral component of treatment for gynecologic malignancies both from a curative (locally advanced cervical cancer) and palliative (bleeding cervical or pelvic mass) standpoint. Critical to understanding how better to serve patients in this regard is understanding both the extent of disease epidemiology and the radiotherapy infrastructure to treat these diseases. In this review, we explore various geographic regions and how they address a unique set of challenges specific to the peoples and culture of the region. We identify common threads across regions, including sparse distribution of radiation equipment, geographic access, and specialized training. We also highlight examples of success in the use of telemedicine and cross-cultural partnerships to help bolster access to training to ensure increased access to adequate and appropriate treatment of gynecologic malignancies.Proton beam therapy is an external beam radiotherapy modality that offers potentially similar efficacy and reduced toxicity compared with photon radiotherapy due to little to no exit dose of radiation beyond the intended target. Improvements in radiotherapy from two-dimensional, to three-dimensional, to intensity-modulated radiation therapy have offered comparable to improved efficacy of radiation therapy with progressive reductions in toxicity. Proton beam therapy may offer further improvements, with multiple dosimetric studies demonstrating potential reductions in exposure of normal tissue to radiation, particularly bowel and bone marrow. Proton beam therapy offers avenues for dose escalation or re-irradiation, which were previously not feasible with photon radiotherapy. Although early clinical data generally demonstrate safety, feasibility, and efficacy in a few series, prospective clinical trials are limited and needed to better define who might benefit from proton therapy. In this review, we discuss the history, dosimetry, available clinical data, and technical needs to deliver high-quality proton therapy.Brachytherapy is an essential component in the curative treatment of many gynecological malignancies. In the past decade, advances in magnetic resonance imaging and the ability to adapt and customize treatment with hybrid interstitial applicators have led to improved clinical outcomes with decreased toxicity. Unfortunately, there has been a shift in clinical practice away from the use of brachytherapy in the United States. The decline in brachytherapy is multifactorial, but includes both a lack of exposure to clinical cases and an absence of standardized brachytherapy training for residents. In other medical specialties, a clear relationship has been established between clinical case volumes and patient outcomes, especially for procedural-based medicine. In surgical residencies, simulation-based medical education (SBME) is a required component of the program to allow for some autonomy before operating on a patient. Within radiation oncology, there is limited but growing experience with SBME for training residviders in low and middle income countries.Quality assurance (QA) in radiation oncology involves all checks and processes that ensure that radiotherapy is delivered in an optimal and intended manner. QA is essential for the accurate delivery of brachytherapy and external beam radiotherapy in patients diagnosed with gynecologic malignancies. Inadequate QA can adversely impact clinical outcomes and reduce the reliability of clinical trials. This review highlights the importance of QA in gynecologic radiation oncology and explores the pertinent issues related to its implementation.Standard treatment of locally advanced gynecological cancers relies mainly on platinum-based concurrent chemoradiotherapy followed by brachytherapy. Current chemotherapeutic drugs are only transiently effective and patients with advanced disease often develop resistance and subsequently, distant metastases despite significant initial responses of the primary tumor. In addition, some patients still develop local failure or progression, suggesting that there is still a place for increasing the anti-tumor radiation effect. Several strategies are being developed to increase the probability of curing patients. Vaginal cancer and vulva cancer are rare diseases, which resemble cervical cancer in their histology and pathogenesis. These gynecological cancers are predominantly associated with human papilloma virus infection. Treatment strategies in other unresectable gynecologic cancers are usually derived from evidence in locally advanced cervical cancers. In this review, we discuss mechanisms by which novel therapies could work synergistically with conventional chemoradiotherapy, from pre-clinical and ongoing clinical data. Trimodal, even quadrimodal treatment are currently being tested in clinical trials. Novel combinations derived from a metastatic setting, and being tested in locally advanced tumors, include anti-angiogenic agents, immunotherapy, tumor-infiltrating lymphocytes therapy, adoptive T-cell therapy and apoptosis inducers to enhance chemoradiotherapy efficacy through complementary molecular pathways. In parallel, radiosensitizers, such as nanoparticles and radiosensitizers of hypoxia aim to maximize the effect of radiotherapy locally.Pelvic radiotherapy is an essential component of cancer therapy for patients with cervical and other gynecological malignancies. The ovaries are particularly radiosensitive, and even low radiotherapy doses may result in impaired or complete loss of ovarian function, causing hormonal disturbances and infertility. Recent advances in both surgery and radiotherapy have facilitated the ability of some patients to maintain ovarian function through ovarian transposition and careful radiotherapy planning. Multidisciplinary discussions should be undertaken to consider which candidates are appropriate for transposition. Generally, patients under age 35 should be considered due to ovarian reserve, likelihood of oophoropexy success, and radioresistance of ovaries. Those patients with small squamous cell tumors, minimal extra-uterine extension, and no lymphovascular invasion or lymph node involvement are ideal candidates to minimize risk of ovarian metastasis. Patients should be assessed and counseled about the risks of ovarian metastasis and the likelihood of successful ovarian preservation before undergoing oophoropexy and starting treatment. [https://www.selleckchem.com/products/i-bet151-gsk1210151a.html GSK1210151A] Oophoropexy should be bilateral if possible, and ovaries should be placed superior and lateral to the radiotherapy field. Studies limiting the mean ovarian dose to less than 2-3 Gray have demonstrated excellent preservation of ovarian function. Intensity modulated radiotherapy and volumetric modulated arc therapy techniques have the potential to further minimize the dose to the ovary with excellent outcomes. The addition of brachytherapy to the treatment regimen will probably cause minimal risk to transposed ovaries. Oophoropexy before radiotherapy may preserve the hormonal function of ovaries for a duration, and fertility might be possible through surrogate pregnancy. Successful ovarian transposition has the potential to improve the overall health and wellbeing, reproductive options, and potentially quality of life in patients with cervical and other gynecological cancers.Stereotactic body radiotherapy (SBRT, also referred to as stereotactic ablative radiotherapy (SABR)) has been used in the treatment of primary and metastatic solid tumors, and increasingly so in gynecologic oncology. This review article aims to summarize the current literature describing the utility of SBRT in the primary, recurrent, and limited metastatic settings for gynecologic malignancies. The use of SBRT in both retrospective and prospective reports has been associated with adequate control of the treated site, particularly in the setting of oligometastatic disease. It is not, however, recommended as an alternative to brachytherapy for intact disease unless all efforts to use brachytherapy are exhausted. While phase I and II trials have established the relative safety and potential toxicities of SBRT, there remains a dearth of phase III randomized evidence, including the use of immunotherapy, in order to better establish the role of this technique as a method of improving more global outcomes for our patients with gynecologic cancers.Epithelial ovarian cancer accounts for around 1.9% of all malignancies and often presents late at an advanced stage. Prognosis is therefore poor. Currently the mainstay of treatment is radical cytoreductive surgery and chemotherapy but, in the past, the standard of care also included adjuvant whole abdominal radiotherapy. This is no longer standard practice, largely due to high toxicity rates and the effectiveness of platinum-based chemotherapy. Presently, a role is emerging for modern radiotherapy techniques in both the salvage and palliative settings. This review aims to examine the historical use of radiotherapy in ovarian cancer before looking forward to its potential future role.