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Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."
Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011
Dr. Shankar P.R.
"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."
Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011 Anuradha
Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.
Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020
Original article / research
Full Version
Dosimetric Comparison of Hippocampal Sparing Whole Brain Radiotherapy by Volumetric Modulated Arc Therapy, Linac-based Intensity-modulated Radiation Therapy and 3-D Conformal Radiation Therapy: A Cross-sectional Study
Correspondence Address :
Preeya Vasanthakumari,
Additional Professor, Department of Radiation Oncology, Government Medical College, Gandinagar, Arpookara, Kottayam-686008, Kerala, India.
E-mail: preeya.anilkumar7@gmail.com
Introduction: Brain metastases are treated with Whole-Brain Radiotherapy (WBRT) using the 3-D Conformal Radiation Therapy (3DCRT) technique. Attempts have been made to perform dosimetric analysis of WBRT with hippocampal sparing using 3DCRT, Volumetric Modulated Arc Therapy (VMAT), and Linac-based Intensity Modulated Radiation Therapy (linac-based IMRT), anticipating technical challenges during contouring and treatment planning.
Aim: To perform a dosimetric analysis and comparison of hippocampal sparing cranial irradiation by 3DCRT, VMAT, and IMRT treatment plans in brain metastases patients.
Materials and Methods: The analytical cross-sectional dosimetric study was conducted from November 2022 to September 2023 at Government Medical College, Kottayam, Kerala, India. Ten patients treated for brain metastases with WBRT using 3DCRT were considered for dosimetric analysis. The Planning Target Volume (PTV) dosimetry and hippocampal dosimetry were studied for all ten patients. The important dosimetric parameters included volume receiving 100% dose, Target Coverage (TC), Homogeneity Index (HI) in PTV dosimetry, the mean hippocampal dose, and maximal hippocampal dose in hippocampal dosimetry. The hippocampus and hippocampal avoidance volume were contoured. Treatment plans for 3DCRT, VMAT, and Linac-based IMRT were generated for each patient’s prescription dose of 30 Gy in 10 fractions. The non-parametric Kruskal-Wallis test was used for data analysis.
Results: The mean whole brain Planned Target Volume (PTV) was 1190 cm3. The mean hippocampal avoidance volume was 30 cm3, which occupied 2.5% of the whole brain PTV. The average median dose received by the hippocampus was 30.05 Gy, 17.1 Gy, and 17.5 Gy for 3DCRT, Linac-based IMRT, and VMAT, respectively. The mean dose for the hippocampus was 31.03 Gy, 17.7 Gy, and 17.5 Gy for 3DCRT, Linac-based IMRT, and VMAT, respectively (p<0.001). VMAT offered better hippocampal sparing compared to IMRT and 3DCRT. On average, VMAT offered a 2% improvement, and 3DCRT offered a 5% improvement in TC compared to IMRT. The HI of 3DCRT was 0.09, IMRT 0.199, and VMAT 0.150.
Conclusion: VMAT and LINAC-based IMRT permit hippocampal-sparing WBRT with adequate target volume coverage and acceptable homogeneity when compared to 3DCRT plans. Thus, the dosimetric study suggests that modern radiotherapy techniques should be advocated for hippocampal-sparing WBRT.
Brain metastases, Hippocampal avoidance, Neurocognitive function
Brain metastases, due to varying malignancies, are usually treated with WBRT. The hippocampus is a complex structure of the human brain associated with memory consolidation and decision-making. It is the grey matter tissue located in the Parahippocampal gyrus inside the inferior temporal horn of the lateral ventricle. The hippocampus, which is an integral part of the limbic system, has four parts: the hippocampus proper (Cornu Ammonis; CA), Dentate Gyrus (DG), subiculum, and Entorhinal Cortex (EC). Neuronal stem cells are located in two neurogenic niches: lining the walls of the lateral ventricle (subventricular zone, SVZ) and the dentate gyrus of the hippocampus (subgranular zone, SGZ). Neural stem cells play a pivotal role in hippocampal neurogenesis. The pyramidal and granule cells generated from mitotically active neural stem cells located in the subgranular zone of the dentate gyrus are associated with memory function. It regulates learning, memory encoding and consolidation and spatial navigation (1). The stem cell niche of the hippocampus, responsible for neurocognitive function, is the most sensitive to the therapeutic doses of WBRT. They are rendered gliogenic, less proliferative and more apoptotic (2),(3). These effects are due to inflammation around the neural stem cells, as stated by Monje ML et al., (4). During WBRT, inflammation of these “stem cell niche” and their damage imparts neurocognitive decline, notably in the memory-related domain (5),(6).
Modern radiotherapy techniques like IMRT and VMAT ensure a conformal avoidance of the hippocampus and may spare patients from radiation-induced neurocognitive decline, without compromising on TC and homogeneity (7). Newer radiation techniques like IMRT utilising Linac-based IMRT and VMAT can conformally spare the hippocampus during cranial radiation. This, in turn, reduces radiation-induced inflammation of the stem cell niche of the hippocampus, mitigating neurocognitive deficits (8). Brain metastases, prophylactic cranial radiation for small cell lung cancer and paediatric malignancies are the common indications for WBRT (8). Testing of hippocampal sparing during WBRT in patients with brain metastases was initiated at the University of Wisconsin (9).
Mostly advanced malignancies of lung, breast, GIT can metastasise to the brain. Whole brain radiotherapy aimed at sterilising the brain metastases was commonly employed. With the advent of targeted and newer chemotherapeutic agents, these patients live longer than what was expected previously (10). Herein, the authors did a dosimetric analysis and comparison of hippocampal sparing cranial irradiation treatment plans. Additional plans were generated for IMRT and VMAT techniques in brain metastases treated with WBRT by 3DCRT. The meaningful difference derived in hippocampal dosimetry by improved radiation techniques might lead to the stepping stone of hippocampal sparing WBRT in the study institution.
The analytical cross-sectional study was conducted from November 2022 to September 2023 at Government Medical College, Kottayam, Kerala. Ten patients treated for brain metastases with WBRT using 3DCRT were considered for dosimetric analysis. Institutional ethical clearance with IRB No. 71/2022 was obtained.
Inclusion criteria: Patients with brain metastases aged 20-70 years, ECOG performance status 0-3, and no previous history of radiation to the brain were included.
Exclusion criteria: Patients receiving WBRT by single radiation dose, metastases located in and around the hippocampus area, and those with a previous history of radiation to the brain were excluded.
Ten patients being treated for brain metastases with WBRT using 3DCRT were considered for dosimetric analysis for the three techniques.
Procedure
Flowchart of methodology is shown in (Table/Fig 1). Patients were immobilised with a thermoplastic head mask and underwent non-contrast CT simulation with 2 mm slices from the vertex to the chin. The CT axial images were imported and fused with axial T2-weighted and gadolinium contrast-enhanced T1-weighted sequence acquisitions Magnetic Resonance Imaging (MRI). The target (whole brain) and the avoidance region (hippocampus) were contoured (Table/Fig 2), and a treatment plan was generated with the Eclipse planning system (Varian Medical Systems, Palo Alto, CA, Version 16) for VMAT, IMRT, and 3DCRT techniques using 6MV photon beams. Thus, three treatment plans advocating the triple-A (AAA) algorithm were generated for each patient.
WBRT with 30 Gy in 10 fractions was delivered by 3DCRT. The dosimetric analysis and comparison of the three treatment plans were conducted, and the parameters were entered. (Table/Fig 3) shows a comparison of dose distribution and Dose-Volume Histogram (DVH) of HAWBRT (Hippocampal Avoidance WBRT) with: (a) 3DCRT; (b) VMAT; (c) IMRT.
Compliance criteria for target and normal tissue planning doses (RTOG 0933):
• V30Gy >95% PTV (V30 Gy- Volume of whole brain PTV receiving 30 Gy)
• D2% PTV <37.5 Gy (D2%- Greatest dose delivered to 2% PTV)
• D98% PTV >25 Gy (D98%- Greatest dose delivered to 98% target volume)
• Hippocampus: Dmin=D 100%--<9 Gy (D100%-Greatest dose delivered to 100% bilateral hippocampi) Dmax=<16 Gy (Dmax-Dose to hottest 0.03 cc of bilateral hippocampi)
The T1 weighted MRI axial sequence was selected for hippocampal contouring. The gray matter was located inferomedial and fimbriae superomedial to the hippocampus. The hippocampus extends from the floor of the temporal horn and proceeds postero-cranially along the medial edge of the temporal horn to terminate at the lateral edges of quadragerminal cisterns. The PTV was the whole brain parenchyma, excluding the hippocampal avoidance region. The hippocampal avoidance region is created by adding a margin of 5 mm to the hippocampus.
Statistical Analysis
Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) 14.0 software. The comparison of the different PTV dosimetry and hippocampal dosimetry among three different techniques was done with the Kruskal-Wallis test (a non-parametric test of one-way ANOVA). Asymptotic significance (2-sided tests) displayed the level of significance at p<0.05.
The total of 10 included patients and tumour characteristics were enumerated in (Table/Fig 4).
The mean whole brain PTV was 1190 cm3 (range 1040-1535 cm3). The mean hippocampal avoidance volume was 30 cm3 (range 21.2-41.6 cm3), which occupied 2.5% (1.8-3.5%) of the whole brain PTV. The median dose received by the hippocampus was 30.05 Gy, 17.1 Gy, 17.5 Gy by 3DCRT, linac-based IMRT, and VMAT, respectively. On average, VMAT offers a 2% improvement and 3DCRT a 5% improvement in TC when compared to IMRT (Table/Fig 5). The mean dose to 100% of the hippocampus was 30.05 (range 29.3-31.1) with 3DCRT, 9.5 Gy (range 8.5-14.9) with IMRT, and 7.8 Gy (range 6.7-12) for VMAT. The mean maximal hippocampal dose was 31.62 Gy (range30.5-32.4), 30.49 Gy (range 29.4-32), and 29.9 Gy (range 24.1-32.3) by 3DCRT, IMRT, and VMAT, respectively. The maximal dose here was more than what was suggested by RTOG, but the dose by VMAT and linac-based IMRT was significantly less when compared to 3DCRT (p=0.010) (Table/Fig 6).
HI signifies the homogeneity of the dose within the target volume as specified by ICRU (International Commission on Radiation Units and Measurements). {HI=D2%-D98%/D median (D50%)} Smaller values for HI signify more homogeneous irradiation of the target volume. The HI of 3DCRT was 0.09, IMRT 0.199, and VMAT 0.150 (p=0.001) (Table/Fig 7).
The dentate gyrus and conus ammonius targeted contouring enables avoidance of the subgranular stem cell compartment (11). In the Gondi V et al., study, the mean hippocampal avoidance volume was 27.5 cm3, which represented 2.1% of the whole brain (7). Here, the mean whole brain PTV was 1190 cm3 (range 1040-1535 cm3). The mean hippocampal avoidance volume was 30 cm3 (range 21.21-41.6 cm3), which occupied 2.5% of the whole brain PTV.
In this study, VMAT offered better hippocampal sparing when compared to IMRT and 3DCRT. In the Wisconsin study of multi-institutional analysis (7), the median hippocampal dose was 5.5 Gy for IMRT and 7.8 Gy for helical Tomotherapy. Thus, helical Tomotherapy offered better hippocampal sparing than linac-based IMRT. The accepted alpha/beta ratio of the CNS is two (2), which is classified as a late responding tissue (12). The pragmatic dose constraint to mitigate long-term neurocognitive decline is the mean dose of the left hippocampus of less than 30 Gy (13). Besides, Jalali R et al., after their analysis of factors affecting neurocognitive decline stated that those patients receiving more than 42 Gy to the left hippocampus suffered greater than a 10% decline in their FSIQ (p=0.048) (14). But RTOG 0933 protocol defined strict constraints to the target and Organ At Risk (OAR) (11). According to the protocol, the dose to 100% of the hippocampus could not exceed 9 Gy, and the maximal hippocampal dose could not exceed 16 Gy. Dose to 100% of the hippocampus exceeding 10 Gy and maximal hippocampal dose exceeding 17 Gy cannot be accepted and require replanning (11).
TC denotes the fraction of the target volume (Vt) receiving at least the prescription dose (Vt pre.dose). For perfect coverage, TC equals one. In the present study, VMAT offers a 2% improvement, and 3DCRT offers a 5% improvement in TC when compared to IMRT. Helical tomotherapy demonstrated a 2% improvement in TC as stated by Gondi V et al., (7). In this study, HI was best for 3DCRT followed by VMAT and then by IMRT. In the Gondi V et al., study, there was a rapid dose fall-off with helical tomotherapy, but homogeneity was acceptable with both IMRT modalities (7).
Hippocampal sparing was achieved with acceptable TC and homogeneity for a prescription dose of 30 Gy in 10 fractions for brain metastases. VMAT and linac-based IMRT significantly reduced the dose to the hippocampus when compared to 3DCRT. The mean maximal dose here is greater than 16 Gy; hence, more meticulous planning and replanning to abide by this constraint would be required in the future. The apparent long-term neurocognitive benefit needs to be evaluated clinically. The study was a dosimetric analysis alone on additionally created VMAT and IMRT plans for each patient. The clinical significance can be ensured only after hippocampal avoidance treatment on patients undergoing WBRT with VMAT and IMRT.
Limitation(s)
The study is only a pilot study with a small number of patients. Here, a dosimetric analysis and comparison of PTV dosimetry and hippocampal dosimetry was done on computer-generated plans for 3D CRT, IMRT, and VMAT. The results may not be replicable or extrapolated unless tried on human subjects. The study only justifies the feasibility of IMRT and VMAT for HSWBRT. The functional benefit of the techniques on the neurocognitive domain could be assessed only after adaptation of these techniques for WBRT.
Accurately delineating the hippocampus and identifying its central location are the two important challenges faced during contouring (RTOG 0933) and when attempting its sparing during IMRT and VMAT. However, by using these techniques for conformal avoidance, the authors could significantly reduce the mean dose received by the hippocampus compared to 3DCRT. Nevertheless, the postulate of mitigating neurocognitive decline needs to be evaluated by a clinical neurological examination, including Full Scale Intelligence Quotient (FSIQ), conducted by a multidisciplinary team of radiation oncologists, neuroradiologists, and neurologists.
DOI: 10.7860/JCDR/2024/66726.19018
Date of Submission: Jul 28, 2023
Date of Peer Review: Oct 03, 2023
Date of Acceptance: Dec 30, 2023
Date of Publishing: Feb 01, 2024
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes
PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Aug 03, 2023
• Manual Googling: Oct 11, 2023
• iThenticate Software: Dec 26, 2023 (20%)
ETYMOLOGY: Author Origin
EMENDATIONS: 7
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