Advances In Treatment Techniques Research Articles

INNV-18. FOCUS ON CURRENT AND EMERGING TREATMENT OPTIONS FOR GLIOMA: A COMPREHENSIVE REVIEW

Abstract This comprehensive review delves into the current updates and challenges associated with the management of low-grade gliomas (LGG), the predominant primary tumors in the central nervous system. With a general incidence rate of 5.81 per 100000, gliomas pose a significant global concern, necessitating advancements in treatment techniques to reduce mortality and morbidity. This review places a particular focus on immunotherapies, discussing promising agents such as Zotiraciclib and Lerapolturev. Zotiraciclib, a CDK9 inhibitor, has demonstrated efficacy in glioblastoma treatment in preclinical and clinical studies, showing its potential as a therapeutic breakthrough. Lerapolturev, a viral immunotherapy, induces inflammation in glioblastoma and displays positive outcomes in both adult and pediatric patients. Exploration of immunotherapy extends to Pembrolizumab, Nivolumab, and Entrectinib, revealing the challenges and variabilities in patient responses. Despite promising preclinical data, the monoclonal antibody Depatuxizumab has proven ineffective in glioblastoma treatment, emphasizing the critical need to understand resistance mechanisms. The review also covers the success of radiation therapy in pediatric LGG, with evolving techniques, such as proton therapy, showing potential improvements in patient quality of life. Surgical treatment is discussed in the context of achieving a balance between preserving the patient’s quality of life and attaining gross total resection, with the extent of surgical resection significantly influencing the survival outcomes. In addition to advancements in cancer vaccine development, this review highlights the evolving landscape of LGG treatment, emphasizing a shift toward personalized and targeted therapies. Ongoing research is essential for refining strategies and enhancing outcomes in the management of LGG.

Ischemic Heart Disease in Pregnancy: Current Understanding and Management Strategies.

Ischemic heart disease (IHD) during pregnancy poses a rare but significant risk to maternal and fetal health, with global incidence rates ranging from 0.7 to 10 cases per 100,000 pregnancies. This review synthesizes current literature on the epidemiology, pathophysiology, clinical presentation, diagnosis, management, and outcomes of IHD in pregnancy. Pregnancy-related IHD encompasses various conditions, including coronary artery disease, spontaneous coronary artery dissection, myocardial infarction with nonobstructive coronary arteries, coronary embolism, and coronary vasospasm. The pathophysiology is multifactorial, involving hemodynamic changes, hormonal influences, and increased hypercoagulability. Clinical presentation may mimic typical pregnancy symptoms, necessitating a high index of suspicion for timely diagnosis. A multidisciplinary strategy is needed for management, taking into account the hazards to the mother and fetus while also taking drug safety and procedural treatments such coronary artery bypass grafting and percutaneous coronary intervention into account. Careful observation and timely management are necessary for complications such as cardiogenic shock, arrhythmias, and thromboembolic events following myocardial infarction. With advancements in treatment techniques and early discovery, the prognosis has improved, although maternal mortality is still a worry. For the purpose of improving results and directing future research endeavors, knowledge and comprehension of IHD during pregnancy are essential.

Recent Advances in Understanding and Management of Arteriovenous Malformations of the Temporal Skin Area

Context: Arteriovenous malformations (AVMs) of the temporal skin area, though less common than cerebral AVMs, pose significant challenges in terms of cosmetic and functional outcomes. Over the past decade, substantial advancements have been made in the understanding and management of these lesions. This paper aims to review the latest developments in the pathophysiology, diagnosis, and treatment of temporal skin AVMs, and to explore ongoing challenges and emerging research directions. Evidence Acquisition: A comprehensive literature search was conducted using databases such as PubMed, Scopus, and Google Scholar. The focus was on research published in the past ten years related to temporal skin AVMs, including reviews, clinical studies, and advancements in treatment techniques. Results: The review discusses the evolution in understanding the pathophysiology of temporal skin AVMs, improvements in diagnostic imaging techniques, and the refinement of surgical and non-surgical treatment approaches. The outcomes, including cosmetic and functional results, and complications associated with various treatments, are also presented. Conclusions: The management of temporal skin AVMs has benefited from multidisciplinary approaches, combining surgery, interventional radiology, and dermatology. However, challenges remain in achieving optimal cosmetic and functional outcomes, necessitating ongoing research and innovation.

Focus on current and emerging treatment options for glioma: A comprehensive review.

This comprehensive review delves into the current updates and challenges associated with the management of low-grade gliomas (LGG), the predominant primary tumors in the central nervous system. With a general incidence rate of 5.81 per 100000, gliomas pose a significant global concern, necessitating advancements in treatment techniques to reduce mortality and morbidity. This review places a particular focus on immunotherapies, discussing promising agents such as Zotiraciclib and Lerapolturev. Zotiraciclib, a CDK9 inhibitor, has demonstrated efficacy in glioblastoma treatment in preclinical and clinical studies, showing its potential as a therapeutic breakthrough. Lerapolturev, a viral immunotherapy, induces inflammation in glioblastoma and displays positive outcomes in both adult and pediatric patients. Exploration of immunotherapy extends to Pembrolizumab, Nivolumab, and Entrectinib, revealing the challenges and variabilities in patient responses. Despite promising preclinical data, the monoclonal antibody Depatuxizumab has proven ineffective in glioblastoma treatment, emphasizing the critical need to understand resistance mechanisms. The review also covers the success of radiation therapy in pediatric LGG, with evolving techniques, such as proton therapy, showing potential improvements in patient quality of life. Surgical treatment is discussed in the context of achieving a balance between preserving the patient's quality of life and attaining gross total resection, with the extent of surgical resection significantly influencing the survival outcomes. In addition to advancements in cancer vaccine development, this review highlights the evolving landscape of LGG treatment, emphasizing a shift toward personalized and targeted therapies. Ongoing research is essential for refining strategies and enhancing outcomes in the management of LGG.

Post-surgery spontaneous pneumothorax: Long-term recurrence rates and follow-up challenges revealed by a written survey.

Spontaneous pneumothorax (SP) is a frequently encountered respiratory condition. Despite advancements in treatment techniques, there is currently no standardized treatment protocol. The aim of this study was to standardize the management of SP by collecting long-term postoperative data through written surveys. Our study included 673 surgeries performed for SP at our institution between January 2011 and December 2019. We administered written surveys via mail to gather data on post-surgery recurrence rates and other related factors. The survey addressed key symptoms, medical consultations, and specific diagnoses of SP after surgery. The effective response rate was 70.7%, with significant differences observed across age groups. Among teenagers, the recurrence rate peaked three years postoperatively, with an ipsilateral recurrence rate of 4.8% and a contralateral incidence rate of 11.8%, both of which were significantly higher than those in other age groups. Additionally, age, sex, postoperative contralateral pneumothorax, and the period before the survey were identified as factors influencing the survey results. This survey highlighted the need for long-term postoperative follow-up for teenagers. While written surveys have limitations, this study provided valuable data for understanding the outcomes of SP. Moving forward, it is advisable to conduct surveys using other effective tools or to continue follow-ups in outpatient clinics.

The need of radiotherapy optimization for glioblastomas considering immune responses.

Glioblastoma is the most common of malignant primary brain tumors and one of the tumors with the poorest prognosis for which the overall survival rate has not significantly improved despite recent advances in treatment techniques and therapeutic drugs. Since the emergence of immune checkpoint inhibitors, the immune response to tumors has attracted increasing attention. Treatments affecting the immune system have been attempted for various tumors, including glioblastomas, but little has been shown to be effective. It has been found that the reason for this is that glioblastomas have a high ability to evade attacks from the immune system, and that the lymphocyte depletion associated with treatment can reduce its immune function. Currently, research to elucidate the resistance of glioblastomas to the immune system and development of new immunotherapies are being vigorously carried out. Targeting of radiation therapy for glioblastomas varies among guidelines and clinical trials. Based on early reports, target definitions with wide margins are common, but there are also reports that narrowing the margins does not make a significant difference in treatment outcome. It has also been suggested that a large number of lymphocytes in the blood are irradiated by the irradiation treatment to a wide area in a large number of fractionations, which may reduce the immune function, and the blood is being recognized as an organ at risk. Recently, a randomized phase II trial comparing two types of target definition in radiotherapy for glioblastomas was conducted, and it was reported that the overall survival and progression-free survival were significantly better in a small irradiation field group. We review recent findings on the immune response and the immunotherapy to glioblastomas and the novel role of radiotherapy and propose the need to develop an optimal radiotherapy that takes radiation effects on the immune function into account.

Clinical outcomes of slow-coagulation continuous-wave transscleral cyclophotocoagulation laser for treatment of glaucoma.

The complications and inadequate efficacy of prior cyclodestructive procedures limited their role in glaucoma management. Recent advances in treatment techniques and parameters for laser cyclophotocoagulation has expanded its role in today's glaucoma practice. In this review, we discuss the treatment outcomes of slow-coagulation continuous-wave transscleral cyclophotocoagulation (CW-TSCPC) as a glaucoma surgical procedure for multiple types of glaucoma in lowering intraocular pressure (IOP). Slow-coagulation TSCPC is a relatively new technique for CW-TSCPC that, unlike the 'pop' power titration technique of laser energy delivery, aims to avoid the production of the 'pop' sound that signals explosive inflammatory energy delivery to the ciliary body and nearby tissue. In slow-coagulation TSCPC, laser energy is applied in a fixed and lower amount over a longer duration, compared with the conventional pop technique. This laser energy approach leads to more stable, reliable, titratable, and selective ciliary body ablation for control of IOP, especially relative to the controversial current use of micropulse TSCPC. Slow-coagulation CW-TSCPC can be used safely, efficiently, reproducibly, and efficaciously in wide range of glaucoma types including those with no history of incisional surgeries, good visual acuity, and medically refractory glaucomas.

Development and Implementation of Proton Therapy for Hodgkin Lymphoma: Challenges and Perspectives.

Simple SummaryHodgkin lymphoma (HL) is a highly curable disease; proton therapy for mediastinal HL irradiation might theoretically reduce late toxicities compared with classical radiotherapy techniques. However, optimal patient selection for this technique is subject to debate. While implementation at a larger scale of proton therapy for HL may face organizational, political, and societal challenges, new highly effective systematic drugs are being widely evaluated for this disease.Consolidative radiation therapy for early-stage Hodgkin lymphoma (HL) improves progression-free survival. Unfortunately, first-generation techniques, relying on large irradiation fields, were associated with an increased risk of secondary cancers, and of cardiac and lung toxicity. Fortunately, the use of smaller target volumes combined with technological advances in treatment techniques currently allows efficient organs-at-risk sparing without altering tumoral control. Recently, proton therapy has been evaluated for mediastinal HL treatment due to its potential to significantly reduce the dose to organs-at-risk, such as cardiac substructures. This is expected to limit late radiation-induced toxicity and possibly, second-neoplasm risk, compared with last-generation intensity-modulated radiation therapy. However, the democratization of this new technique faces multiple issues. Determination of which patient may benefit the most from proton therapy is subject to intense debate. The development of new effective systemic chemotherapy and organizational, societal, and political considerations might represent impediments to the larger-scale implementation of HL proton therapy. Based on the current literature, this critical review aims to discuss current challenges and controversies that may impede the larger-scale implementation of mediastinal HL proton therapy.

Efficacy of Complementary Therapies in the Quality of Life of Breast Cancer Survivors.

Breast cancer (BC) is the most common cancer diagnosed in women and the second most common cancer overall, ranking as the fifth cause of death from cancer. The chronicity of the disease produces long-term physiological and psychological manifestations, which adversely affect the quality of life of the individual. The primary treatment while managing cancer presents with various debilitating side effects. With the recent advances in treatment techniques that have improved the survival rate, patients suffer from continuing posttreatment complications. Patients seem to cope well with the stress of treatment of BC and sustain a normal life; however, the deterioration in physical well-being makes the patient functionally inefficient. Exercise has been proven to be an effective, safe, and feasible tool in combating the adverse effects of treatment, prevents complications and decreases the risk of BC-specific mortality. This review briefly presents an overview of the burden of the disease and its management strategies. Owing to the heterogeneity of the population and the multitude of therapies they receive, the response of each patient to treatment is different and so is the magnitude of adverse effects. The review discusses the late sequelae following treatment and evidence supporting the role of physical activity in their management. In conclusion, there is a need for personalized physical activity plans to be developed to suit the individual and their circumstances.

Radiobiology of re-irradiations

The treatment options for recurrent tumors are limited. Re irradiation is being increasingly considered as an option, in view of the advances in treatment techniques, particularly the ability to document doses, overlay plans, intensity modulation, and image guidance. preclinical and clinical studies has been to estimate the total cumulative doses (EQD2) also termed as normalized total dose (NTD) that can be delivered to various tissues. In this review article reirradiation radiobiology of different tissues and dose fractionation have been discussed.

Radiation and subsequent reirradiation outcomes in the treatment of diffuse intrinsic pontine glioma and a systematic review of the reirradiation literature

PurposeDiffuse intrinsic pontine glioma (DIPG) is a devastating pediatric disease, with a median survival of <1 year. Here, we review our institution's DIPG experience over an 8-year interval and perform a systematic review of the literature, specifically evaluating reports of reirradiation (reRT) for DIPG. Methods and materialsWe retrospectively reviewed the medical records of 26 patients who underwent definitive intensity modulated radiation therapy (IMRT) for DIPG at a single institution between 2007 and 2015. Three of these patients underwent reRT for progressive disease. Clinical endpoints, including progression-free survival and overall survival (OS), were assessed. We then performed a thorough PubMed search of the literature discussing reRT for patients with DIPG. ResultsTwenty-four of the 26 patients (92%) completed the initial course of radiation (54 Gy in 1.8-Gy fractions using IMRT). Median age at diagnosis was 6.0 years (range, 2.0-26.5). With respect to systemic therapy, 1 (4.2%) received no systemic therapy, 1 (4.2%) received concurrent systemic therapy alone, 4 (16.7%) received adjuvant therapy alone, and 18 (75%) received a combination of concurrent and adjuvant therapy. Median follow-up time was 11 months from the date of initial diagnosis. Median OS for the cohort was 12 months, with a 1-year OS of 51%. The 3 patients who underwent reRT received 20 Gy in 10 daily fractions using IMRT alone with no treatment toxicity noted. ConclusionsRadiation therapy is essential in the definitive management of DIPG. With advances in treatment techniques, it is feasible to reirradiate select patients with progressive disease; however, further research is warranted to optimize dose, delivery, and patient selection in the recurrent/progressive setting. In the future, it may be reasonable to propose more focal delivery of reRT (ie, hypofractionated radiation) in select patients with the goal of reducing treatment time and providing effective palliation.

MiR-10b decreases sensitivity of glioblastoma cells to radiation by targeting AKT.

BackgroundGlioblastomas are the most aggressive brain tumors with extremely poor prognosis despite advances in treatment techniques. MiR-10b is highly expressed in glioblastoma and regulates cell proliferation, migration and invasion. Here, we examined the role of MiR-10b on radiotherapy of glioblastomas.MethodsMiR-10b mimic or anti-MiR-10b inhibitor was transfected in glioblastoma cells. WST-1 assay was used to examine the effect of MiR-10b on proliferation of transfected glioblastoma cells after radiation treatment. Apoptosis was examined by caspase 3/7 activity and TUNEL assay. The western blot was used to evaluate protein expression.ResultsAltered expression of MiR-10b changed the radiation-induced inhibitory effect on proliferation of glioblastoma cells with dose-dependent manner. MiR-10b decreased radiation-induced apoptosis in glioblastoma cells by activation of caspase 3/7 and inhibition Bcl-2 expression. MiR-10b enhances migration and invasion of glioblastoma cells in presence of radiation. In addition, MiR-10b decreased the sensitivity of glioblastoma cells to radiotherapy by activation of p-AKT expression.ConclusionsMiR-10b might be a potential biomarker to predict radiotherapy response and prognosis in glioblastomas.

Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study

The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient׳s neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to the hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient׳s data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain.

Successful Transcatheter Closure of a Congenital High-Flow Portosystemic Venous Shunt With the Amplatzer Vascular Plug II

Congenital portosystemic venous shunt is extremely rare and should be treated. Advances in treatment techniques allow for patients to be treated safely. We present a 9-year-old boy with a large congenital portosystemic venous shunt. The shunt was occluded interventionally with the Amplatzer vascular plug II. Our case was unique with its clinical manifestation, the use of a 22-mm Amplatzer vascular plug II, and the presence of the patient's 1-year follow-up.

Advances in Treatment Techniques

Radiation therapy (RT) is an essential component of the management of many cancers. Traditionally, a course of external bream RT often involved daily treatments for a duration of 6 weeks or longer in some instances. Now, however, emerging clinical evidence indicates that, for some common cancers, the total length of treatment can be substantially shortened, offering convenience to patients and opportunities for resource utilization efficiencies. This trend toward so-called hypofractionated RT has been supported by hypothesis-driven clinical research guided by a combination of radiobiological and clinical insights and technological enhancements. The present review presents the rationale behind and current status of hypofractionation for prostate, breast, and medically inoperable early stage lung cancer.

Advances in Treatment Techniques

Treatment planning and radiation delivery techniques have advanced significantly during the past 2 decades. The development of the multileaf collimator has changed the scope of radiotherapy. The dynamic conformal arc technique emerged from traditional cone-based conformal arc therapies, which aim to improve target dose uniformity and reduce normal tissue doses. With dynamic conformal arc, the multileaf collimator aperture is shaped dynamically to conform to the target. With the advent of intensity-modulated radiotherapy (IMRT), the concept of arc therapy in combination with IMRT has enabled better-quality dose distributions and more efficient delivery. Helical tomotherapy has been developed to treat targets sequentially by modulating the beam intensity in each "slice" of the patient. Helical tomotherapy offers improved dose distributions for complicated treatments, such as whole-body radiation. Intensity-modulated arc therapy has been studied to modulate fluences in a cone beam rather than fan beam geometry to improve delivery efficiency. This article reviews arc-based IMRT, intensity-modulated arc therapy, and helical tomotherapy techniques. We compare the dosimetric results reported in the literature for each technique in various treatment sites. We also review the application of these techniques in specialized clinical procedures including total marrow irradiation, simultaneous treatment of multiple brain metastases, dose painting, simultaneous integrated boost, and stereotactic radiosurgery.

Secondary Cancer Risks in Out-of-field Organs for 3-D Conformal Radiation Therapy

The risk of secondary cancers after radiation therapy has become an important issue, mainly because advanced treatment techniques such as 3-D conformal radiation therapy (CRT) and intensity-modulated radiation therapy (IMRT) tend to increase the radiation dose to out-of-field organs. Moreover, cancer patients’ average survival period, following those advances in treatment techniques, also has increased, effectively raising the risks for the same levels of radiation exposure. In the present study, the secondary cancer risks to out-of-field organs were determined for some representative cases of 3-D CRT by measuring organ doses with LiF thermoluminescence (TL) dosimeters and an ATOM TM male phantom. Our results show that the secondary cancer risks are similar (difference: < 20%) for 6 and 10 MV X-ray beams for the same prostate treatment case. The total secondary cancer risks of the out-of-field organs were on the order of 2-4% for the treatment cases considered in the present study.

Long‐term clinical outcomes following treatment of childhood craniopharyngioma

To review our institution's experience with treatment of craniopharyngioma in children, and to report long-term treatment outcomes stratified by treatment era to assess whether modern treatment techniques result in improvements in local control and survival. We retrospectively reviewed the records of 100 children who underwent surgery for craniopharygioma at Children's Hospital Boston (CHB) from August 1976 to March 2003. Of these, 79 children (median age 8.5 years) had initial treatment at CHB and sufficient follow-up data to be included in this analysis. We report their treatment course, recurrence rates, and treatment-related morbidity. We compared the results in two different treatment eras based on changes in surgical approach at CHB. Thirty-six patients underwent initial treatment with surgery alone; 63% treated prior to 1988 recurred and 36% treated after 1988 recurred. Recurrence rates following combined modality therapy (CMT) with limited surgery followed by radiation were 21 and 5% in the pre- and post-1988 eras, respectively. Accounting for treatment era, patients treated with surgery alone were 7.7 times as likely to recur as those treated with CMT (95%CI: 2.0, 28.7). In the Cox regression model, there was no significant difference in local control or overall survival based on treatment era; initial treatment remained the only statistically significant variable (P = 0.02). Advancements in treatment techniques have improved local control in children diagnosed with craniopharyngioma. The excellent survival rates necessitate long-term patient follow-up to identify and manage any treatment-related effects, including second tumors, vascular abnormalities, and endocrinopathies.

The impact of age and comorbidity on survival outcomes and treatment patterns in prostate cancer

The management of localized prostate cancer is based on stage, grade, PSA, and subjective assessment of comorbidity and life expectancy. Over the last 15 y, stage migration and the improved use of Gleason sum, PSA and TNM staging have led to many treatment options for patients with newly diagnosed localized prostate cancer. At the same time, advances in treatment techniques have helped decrease the long-term complications of surgery and radiotherapy. However, the importance of age and comorbidity, in survival outcomes and treatment decision-making has been largely overlooked. Currently, stage, grade, and PSA are the only quantifiable variables consistently used in research and treatment decision-making. Comorbidity and life expectancy have remained largely subjective variables. Increasing longevity and a rapidly aging population have made age and comorbidity increasingly important factors in clinical research and treatment decision-making. This article reviews the importance of age and comorbidity on treatment decisions and survival outcomes in prostate cancer, as well as their use as objectively quantifiable variables. Examples from the general oncology literature are given. The overview also examines validated comorbidity indices and advocates the use of the Charlson Comorbidity Index (CCI) in research outcomes and treatment decision-making in prostate cancer. Several clinical vignettes are provided to demonstrate the potential clinical utility of the CCI as applied to prostate cancer.

Challenges in sports medicine

Sports medicine has provided significant advances in treatment techniques and contributions to community health. Some of the challenges facing sports physicians today include establishing the safety and efficacy of treatment techniques, involvement in developing and promoting exercise programs, sports supplements and the anti-doping code. (non-author abstract)