AUCTORES
Globalize your Research
Review Article
*Corresponding Author: Steve Rebeca, Department of Neurology , Mexico
Citation: Steve Rebeca, Cindy Carlson. (2017) Metastatic Brain Tumors: Current Therapeutic Options through Surgery and Radiation Therapy, Doi: 10.31579/2578-8868/055
Copyright: © 2017. Steve Rebeca This is an open-access article distributed under the terms of The Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 20 February 2017 | Accepted: 09 March 2017 | Published: 15 March 2017
Keywords: brain tumour; neurological disorders;Neurotherapeutics
Metastatic tumours involving the brain overshadow primary brain neoplasms in frequency and are an important complication in the overall management of many cancers. Importantly, advances are being made in understanding the molecular biology underlying the initial development and eventual proliferation of brain metastases. Surgery and radiation remain the cornerstones of the therapy for symptomatic lesions; however, image-based guidance is improving surgical technique to maximize the preservation of normal tissue, while more sophisticated approaches to radiation therapy are being used to minimize the long-standing concerns over the toxicity of whole-brain radiation protocols used in the past. Furthermore, the burgeoning knowledge of tumour biology has facilitated the entry of systemically administered therapies into the clinic. Responses to these targeted interventions have ranged from substantial toxicity with no control of disease to periods of useful tumour control with no decrement in performance status of the treated individual. This experience enables recognition of the limits of targeted therapy, but has also informed methods to optimize this approach. This Review focuses on the clinically relevant molecular biology of brain metastases, and summarizes the current applications of these data to imaging, surgery, radiation therapy, cytotoxic chemotherapy and targeted therapy.
History
Surgical intervention for cerebral metastasis has been performed since the late 1800s.However, early attempts often resulted in devastating complications, including infections and high surgical mortality. even after improvements such as the use of perioperative antibiotics and advances in surgical illumination and magnification, and it took several decades for the benefits of surgical intervention to become widely accepted. Regarded as a less invasive therapeutic option, whole-brain radiation therapy (WBRT) was first recognized, to our knowledge, in the 1950s9 and demonstrated a substantial survival benefit, quickly becoming the standard of care. Over the next several decades, the benefits of surgical resection versus radiotherapy remained a contentious issue secondary to the paucity of literature. Moreover, early treatment with WBRT was hampered by the insufficient resolution of imaging modalities, which rendered brain metastasis essentially an “invisible” problem. Hence, radiotherapy gained acceptance as the standard of care, whereas surgical interventions were reserved for special circumstances.10 The landscape of brain tumor therapy experienced a major transformation in the early 1970s with the advent of computed tomography and then again in the 1980s with the implementation of magnetic resonance imaging. The ability to better visualize intracranial lesions and evaluate postsurgical results once again sparked interest in surgical resection of brain metastases.
Randomized Study Protocol
In a randomized controlled trial from 1990, demonstrated longer survival for patients with brain metastasis who underwent surgical resection compared with the survival of patients who underwent radiation alone (median survival times of 40 weeks and 15 weeks, respectively). These findings were later confirmed by other studies using larger patient samples. showed that surgical resection increased survival time for patients with 3 or fewer brain metastases and that the prognosis for these patients was similar to that of patients who underwent surgical resection for a solitary lesion. went on to evaluate WBRT as a surgical adjunct in their 1998 prospective trial, demonstrating that postoperative WBRT attenuated metastatic recurrence at the index site of metastasis, as well as at remote brain locations. Interestingly, the study did not show statistically significant differences in length of survival in patients who underwent adjunct radiation compared with those who underwent surgical resection only.
At nearly the same time that Patchell's research was being conducted, in 1993 a group of Swedish researchers was the first to report their experience with brain metastases by using gamma-knife (GK) radiosurgery alone. Initial results from this 16-year study were favorable, with a 94% control rate for treated lesions, a 7-month mean survival time, and 13% of patients experiencing radiation-associated adverse events.14 Other studies using linear accelerator stereotactic radiosurgery achieved results similar to those of the Swedish group.15,16
Over the past 2 decades, the treatment of patients with brain metastases has progressed to include a multitherapeutic approach as standard of care (Table). Various combinations of surgical resection, WBRT, and stereotactic radiosurgery are being evaluated to assess which can provide the best available outcomes for this patient population. Patient-specific variables such as age, functional status, and systemic control of primary disease, as well as number, size, and location of metastatic lesions, become increasingly important in guiding treatment recommendations. Although controversy regarding optimal therapeutic avenues still exists, it is essential for physicians to consider all options when treating patients with brain metastasis.
The importance of Angiogenesis
The growth of metastatic brain tumours is critically dependent on angiogenesis, and thus therapies targeting this process might be important in the management of brain metastasis. Disordered angiogenesis results in structural and functional abnormality of tumour-associated blood vessels, characterized by defective endothelial cells, pericyte covering and basement membranes.These abnormalities can directly restrict the delivery of oxygen, leading to intratumoural hypoxia. Impaired efficacy of systemically administered anti-cancer therapeutics and agents used in radiation therapy due to limited perfusion of the cancer tumour bed and thus exposure to the drug, might lead to the establishment of functional sanctuary sites that enable the growth of cancer cells.
Brain Metastases—Surgical Management
Historical and current concepts
Advancements in neuroanaesthesia, instrumentation and imaging technologies, as well as improvements in standard tools, such as the operating microscope, now enable neurosurgeons to perform surgery more safely than ever before. Indeed, in 2010, the first evidence-based compendium for the treatment of patients with brain metastases published a level 1 recommendation for surgical resection combined with radiation therapy to prolong life in relatively young patients with good functional status and a newly diagnosed solitary brain metastasis.
Surgical decision making
Perhaps the most critical aspect of the surgical management of brain metastasis is the decision to proceed with an operation. Careful patient selection based on the current body of evidence is of paramount importance. Currently, class I evidence is available in support of surgical resection followed by WBRT in patients with a newly diagnosed solitary brain metastasis, without advanced systemic disease, who spend more than 50% of their time out of bed.
Radiation Therapy
Whole-brain Radiation Therapy
WBRT has historically been used as the primary non-surgical therapeutic modality for the treatment of brain metastasis (previously reviewed elsewhere. This trend was due, in part, to the limited chemotherapeutic options demonstrated to be efficacious. On the basis of a recursive partitioning analysis of data from patients treated between 1979 and 1993 on previous RTOG protocols, even patients with brain metastasis who had the best prognosis had a median survival of only 7 months after WBRT alone. However, with improvements in systemic therapies for a variety of cancers, patient survival has now increased, even among those with metastatic disease.In this context, WBRT alone is increasingly found to be inadequate in the long-term control of brain metastasis. In addition, with these improved outcomes, many patients in whom control of brain disease is achieved with WBRT are surviving to experience the considerable neurocognitive sequelae and declines in quality of life that are associated with this treatment.The classic neuro cognitive toxicity associated with WBRT in adults is a moderate-to-severe dementia that occurs several months to years after treatment. DeAngelis et al.observed a 2–5% incidence of severe dementia in populations of patients who had undergone WBRT (with or without surgical resection) for brain metastases, although these authors estimated that a markedly higher incidence of dementia would have been found if less-severe cases of neurological decline were also included. An early neurocognitive decline, predominantly in verbal memory, occurring 1–4 months after WBRT has also been described.The degree of neuro-cognitive decline in patients with brain metastasis can be further confounded by the effects of metastasis at presentation or recurrence and therapeutic interventions (that is, chemotherapy) on cognitive function.
Systemic Therapy for Brain Metastases
Patient survival following the development of brain metastasis is typically measured in weeks to months, although considerable variability is observed based on the size, number and location of the metastases, as well as the histological type of cancer involved. Whereas the overall 2-year survival rate in patients with brain meta stasis is 8.1%, 2-year survival after diagnosis of brain metastasis is less than 2% in patients with SCLC, but as high as 24% in patients with ovarian cancer.Contemporary data from patients with oligometastasis to the brain treated primarily with local surgical or radiation therapy reveal a more encouraging median overall survival of 16 months from the time of brain meta stasis diagnosis. As mentioned earlier, the proclivity of certain cancer types to spread to the brain is an intriguing phenomenon whose biological mechanisms remain to be clarified. The so-called ‘seed and soil’ hypothesis implicates key biological mechanisms that permit the development of metastatic tumour deposits in the brain. Signalling through HER2, EGFR, HPSE and Notch1-related pathways might mediate specific biological processes important to tumour growth and metastatic spread, including angiogenesis, epithelial–mesenchymal transition, anchorage independent growth and resistance to anoikis, as well as resistance to standard therapeutic interventions. Other than the use of antiangiogenic agents, the exploitation of these biological processes for therapeutic intervention in the context of brain m etastasis remains mostly limited to preclinical studies.
Targeted molecular therapy
For several years, the mainstay of therapy for brain metastasis from a chemotherapeutic standpoint has been temozolomide. Subsequent to the discovery of BRAF mutations in a majority of melanomas, BRAF inhibitors have been increasingly used to treat this disease, as well as associated brain metastases Initial evidence of the potential promise of BRAF-targeted agents in the clinical management of melanoma-related brain metastasis came from early phase clinical trials. In seven patients with brain metastases, a BRAF inhibitor induced CNS tumour shrinkage, and complete responses were observed in three patients. In a phase I trial, in which the majority of patients had BRAF-mutant melanomas, in addition to other BRAF mutant tumours, dabrafenib treatment was associated with a reduction in the size of brain lesions, and four patients achieved complete resolution of all brain lesions normal serum lactate dehydro genase levels seemed to be a predictor of response to dabrafenib.The intriguing observation of intra cranial responses to dabrafenib in this phase I trial led to a prospective open-label phase II trial of dabrafenib in patients with previously untreated brain metastasis or with progressive brain lesions following initial local treatment .Overall disease control in patients with metastases expressing Val600Glu (V600E) BRAF was 79%, but complete responses were rare, and the efficacy of this compound was generally decreased in the tumours with the Val600Lys (V600K) BRAF mutation subtypes.
Conclusions
Surgery and radiation therapy have important roles in the management of metastatic brain tumours and, depending on one’s definition, could be considered targeted therapies. As such, they remain the ‘go to’ modalities for the treatment of most metastatic brain tumours, particularly at the time of initial diagnosis. However, these interventions are responsible for well-recognized and substantial adverse events in some cases. Effective strategies to minimize these problems would be of great advantage to the patients with metastatic CNS lesions. The achievable technical improvements possible in surgical and radiation techniques are limited and ultimately medicinal means of management, probably relying on novel systemic targeted therapies, will be necessary to attain this goal and to improve outcomes in patients with brain metastases.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
