Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

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Professor & Head,
Department of Dermatolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


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

Important Notice

Original article / research
Year : 2022 | Month : March | Volume : 16 | Issue : 3 | Page : XC01 - XC05 Full Version

Comparison of Sequential Boost and Simultaneous Integrated Boost Volumetric Modulated Arc Therapy in Treatment of Head and Neck Carcinoma: A Prospective Interventional Study


Published: March 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/50041.16076
Abhishek Arora , Ramesh Purohit , Kiran chigurupalli , Menal Bhandari , AR Gupta , Shalu Peter

1. Resident, Department of Radiation Oncology, Geetanjali Medical College and Hospital, Udaipur, Rajasthan, India. 2. Assistant Professor, Department of Radiation Oncology, Geetanjali Medical College and Hospital, Udaipur, Rajasthan, India. 3. Assistant Professor, Department of Radiation Oncology, Geetanjali Medical College and Hospital, Udaipur, Rajasthan, India. 4. Assistant Professor, Department of Radiation Oncology, Geetanjali Medical College and Hospital, Udaipur, Rajasthan, India. 5. Professor, Department of Radiation Oncology, Geetanjali Medical College and Hospital, Udaipur, Rajasthan, India. 6. Medical Physicist, Department of Radiation Oncology, Geetanjali Medical College and Hospital, Udaipur, Rajasthan, India.

Correspondence Address :
Ramesh Purohit,
24-25, Gopal Park, Shobhagpura, Udaipur, Rajasthan, India.
E-mail: dr.ramesh1010@gmail.com

Abstract

Introduction: Volumetric Modulated Arc Therapy (VMAT) is a radiotherapy in head and neck cancer can be delivered by two boost techniques: Sequential Boost (SEQ) and Simultaneous Integrated Boost (SIB). There is still limited data comparing these two techniques.

Aim: To compare SEQ and SIB planning techniques of VMAT in patients of Head And Neck Squamous Cell Carcinoma (HNSCC)in terms of disease response and acute toxicities.

Materials and Methods: A prospective interventional study was conducted at Geetanjali Medical College and Hospital, Udaipur, Rajasthan, India from January 2019 to December 2020. Total of 52 patients of HNSCC planned for radical chemoradiation were enrolled into two study arms SEQ-VMAT and SIB-VMAT. Chemotherapy was given with weekly cisplatin 40 mg/m2. Dosimetric comparison was done using Dose Volume Histogram (DVH) analysis. Response evaluation was done as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at 8-10 weeks follow-up. Acute toxicity evaluation was done as per Radiation Therapy Oncology Group (RTOG) toxicity grading. Statistical analysis was done using Statistical Package for Social Sciences (SPSS) version 20.0 software.

Results: A total of 52 subjects were included in the study, out of which 26 subjects were in each group. No significant difference was observed in demographic data in terms of age 56.2 vs 53.5 years, sex (24 males and 2 females in both the arms), disease site (oropharynx is the most common site 38.5% in both arms) and stage (IVA 69.2% in SEQ arm vs 46.2% in SIB arm and III 30.8% in SEQ arm vs 42.3% in SIB arm). Dosimetric data was comparable between the two arms. SIB-VMAT shows significantly higher incidence of acute dermatitis (grade1 dermatitis at two weeks 69.2% vs 38.5%, p=0.0279 and grade 2 dermatitis at six weeks 84.6% vs 38.5%, p=0.0007) and acute mucositis (grade 1 mucositis at two weeks 84.6% vs 38.5%, p=0.0007) as compared to SEQ-VMAT. SEQ-VMAT shows significantly higher incidence of dysphagia (grade 1 at four weeks 84.5% vs 50%, p=0.0087). No significant differences were observed in terms of xerostomia and laryngeal toxicity. No significant difference in overall response was observed between SIB vs SEQ (complete response 65.4% vs 53.85% p=0.40).

Conclusion: SEQ appears better in terms of acute toxicities but SIB was more convenient as no re-planning was required.For head and neck radiotherapy SIB and Sequential VMAT are comparable in terms of overall response.

Keywords

Chemoradiation, Head and neck, Radiotherapy

With over 2,00,000 cases diagnosed in 2018, HNSCC cancers are one of the most common cancers in the Indian population (1). In India, these tumours often present at a locally advanced stage (2). Radiotherapy plays an important role in the treatment of HNSCC cancers, usually as curative treatment in pharyngeal, laryngeal and advanced oral cancer (3). Radiotherapy for head and neck cancers can be challenging due to the complex anatomy and these tumours often located within close proximity to critical structures which can limit radiation dose (4) VMAT is an advanced technique of Intensity-modulated Radiation Therapy (IMRT) which can achieve high conformity of dosage to target volumes with better sparing of normal tissues (5). VMAT also has the potential to offer additional advantages, such as reduced treatment delivery time compared with conventional static field Intensity Modulated Radiotherapy (IMRT) (6),(7).

VMAT allows treatment delivery by two different approaches: SEQ and SIB (8). In SEQ technique, radiation dose is delivered in different phases with same dose per fraction. The SIB-IMRT technique is of particular interest because it can be used to increase the fraction dose to the boost volume while, at the same time, keeping the dose to the elective volume at a lower level (9). SIB technique can also lead to reduction in overall treatment time and increase in both prescribed dose and biological dose (10) There is limited data for normal tissue response in head and neck cancers treated with SIB technique. There is a substantial difference between the radiobiological response of the small high dose areas treated with increased dose per fraction inside intermediate dose volumes. Hence, there is a need to redefine the dosimetric and volumetric relationship for SIB (11). Farzin M et al., have compared SIB vs. SEQ at other sites of body like high grade glioma of brain (12). Hence, present study aimed to compare the SEQ and SIB techniques of VMAT in patients of head and neck carcinomas in terms of acute toxicity and treatment response.

Material and Methods

This prospective interventional study was conducted in Department of Radiation Oncology, Geetanjali Medical College and Hospital, Udaipur, Rajasthan, India. The study was done from January 2019 to December 2020 with a median follow-up of 12.5 months. Total of 52 patients of biopsy proven squamous cell carcinoma of head and neck region were recruited in the study after an approval from Institutional Ethics Committee (IECNo.GU/HREC/EC/2019/1558)and written informed consent were obtained.

Inclusion criteria: Histopathologically proven primary HNSCC of either sex, who had calorie intake >1500 cal/day were included in the study.

Exclusion criteria: Patients with severe uncontrolled co-morbidities, pregnant and lactating women, those who had received neoadjuvant chemotherapy or prior radiotherapy and postoperative patients were excluded from the study.

Sample size calculation: 95% confidence level, 80% power of study, pooled prevalence=0.27 (Pooled prevalence was calculated by an experienced statistician of the institute) and difference in proportion=0.25. Therefore, sample size was 24 for each group. Considering a 10% dropout rate, the sample size came out to be 24+2 for each study group. Hence, n=26 for each study group.

Procedure

Patients of either sex above the age of 18 years with Eastern Cooperative Oncology Group (ECOG) performance status (13) of less than or equal to two were randomised into two arms, and treated with either SEQ-VMAT or SIB-VMAT. Patients were randomised in two study groups using online randomising software available at www.randomiser.org-

- SEQ-VMAT
-SIB-VMAT

Pre-treatment evaluation including nutritional evaluation was done prior to treatment as per National Comprehensive Cancer Network Guidelines (NCCN) (13). Assessment of extension of disease and staging was done by American Joint Committee of Cancer (AJCC) criteria along with clinical examination laryngoscopy, Computed Tomography (CT) scan, Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET) scan as required (14).

Treatment planning: All patients were immobilised in the supine position with a tailored head-shoulder four clamp thermoplastic mask to undergo CT simulation with slice thickness of 2.5 mm on GE Optima CT520 simulator. Target volume delineation was performed according to the International Committee for Radiological Units (ICRU) 83 guidelines (15). Gross Tumour Volume (GTV) was defined as the gross extent of tumour shown by CT, MRI and PET, including all involved (positive) lymph nodes. On the basis of the primary tumour size and involved node, Clinical Target Volume- High Risk (CTV-HR), CTV- Intermediate Risk (CTV-IR) and CTV-Low Risk (CTV-LR) were contoured. Treatment volume definitions and expansions were consistent between SIB and SEQ groups and were individualised as per institutional practice. Normal and avoidance structures were contoured based on their anatomic definitions. Organs at risk included: spinal cord, brain stem, left and right parotids; larynx, oesophagus, trachea, mandible, pharyngeal constrictors and uninvolved oral cavity. Whenever close to the Planning Target Volume (PTV), eyeballs, optic nerves, and optic chiasm were contoured. PTV margin of 3 mm was generated over CTV for all patients. The dose was prescribed to the PTV using 95% isodose line in both the arms. The dose constraints to Organ At Risk (OAR) were prescribed using Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC) (16). Treatment planning was then performed using Monte-Carlo Optimiser on MONACO v5.11. VMAT plans were generated in both the study groups and plans were evaluated using dose-volume histograms. Dosimetric assessment was done using DVH.

Treatment execution: Treatment was executed on Elekta Versa HD Linear Accelerator. Online image guidance in form of X-ray Volumetric Imaging (XVI) version 5.0 was taken daily or alternate days as per institutional practice. In SEQ boost arm, a 2 gray (Gy) dose per fraction was delivered in different phases and for SIB arm, dose ranging from 1.6 Gy to 2.2 Gy per fraction was delivered in a single treatment plan. For SEQ arm, planning was done in a phased manner. Modifications to original plan were made first at the end of fifth week and then at end of sixth week. Dose prescription, specification and reporting were performed according to ICRU 50 and 62 recommendations. All the patients were treated with conventional dose fractionation using a five days per week treatment schedule.

Chemotherapy as indicated in both the study groups, consisted of weekly cisplatin 40 mg/m2 with a ceiling dose of 70 mg. All patients had consultation with dietician and whenever required nasogastric feeding tube was placed, if patient was unable to maintain nutrition. The acute toxicities were documented as per the RTOG Toxicity Criteria included skin, mucosa, salivary glands, pharynx/oesophagus and larynx. Response Evaluation Criteria In Solid Tumours (RECIST) v1.1 (17) was used for response evaluation at the end of 8-10 weeks after the completion of radiotherapy. Patients were assessed clinically, laryngoscopic examination and imaging with CT/MRI/PET CT scan as required.

Statistical Analysis

Data was presented as mean, standard deviation, median (range), or percentage. Statistical Analysis was done using the SPSS version 20.0 (Chicago, IL). Chi-square test and t-test were used for comparison of qualitative and quantitative variables respectively. The p-value less than 0.05 were considered significant.

Results

Total of 52 patients (26 patients in SEQ VMAT group and 26 patients in SIB VMAT group) were included and data was collected for analysis. Demographic data showed no significant difference in both treatment arms in terms of age (56.2 years in SEQ vs 53.5 years in SIB arm, p-value=0.41), sex (24 males and 2 females in both the arms), disease site{oropharynx is the most common site 38.5% (10/26) in both arms} and stage at presentation {stage IVA constitutes 18(69.2%) patients in SEQ arm vs 12 (46.2%) patients in SIB arm and stage III constitutes 8 (30.8%) patients in SEQ arm vs 11 (42.3%) in SIB arm} (Table/Fig 1). Majority of the patients were males {24(92.3%) in both the arms}.

Toxicity assessment showed that 10 (38.5%) patients in SEQ arm experienced grade 1 acute dermatitis as compared to 18 (69.2%) patients in SIB arm at the end of 2 weeks. Similarly, Grade 2 Dermatitis was observed in 10 (38.5%) patients in SEQ arm vs 22 (84.6%) patients in SIB arm at the end of six weeks (Table/Fig 2). Patients experiencing grade 1 acute mucositis were 10 (38.5%) patients in SEQ arm vs 22 (84.6%)SIB arm at the end of week-2 (Table/Fig 3). Most of the patients observed either grade 1 or grade 2 acute xerostomia. Grade 3 or 4 acute xerostomia was observed in none of the patients (Table/Fig 4). No major differences were observed in terms of dysphagia and acute laryngeal toxicity in both the study arms (Table/Fig 5), (Table/Fig 6). Complete response was observed in 14 (53.8%) in SEQ arm vs 17 (65.4%) patients in SIB arm, p-value=0.40 while a partial response was observed in 12 (46.1%) patients in SEQ arm vs 9 (34.6%) patients in SIB arm, p-value=0.40 when assessed at 8-10 weeks post-treatment (Table/Fig 7).

Dosimetric analysis was done comparing the mean doses to organs at risk for both the study groups and Planning Target Volume (PTV) coverage. No difference was observed in terms of target coverage for both techniques. Mean dose to larynx was 44.31±8.72 Gy in SEQ arm and 43.57±8.17 Gy in SIB arm, p-value=0.79. Similarly, dose to left and right parotid gland were 24.4±1.94 Gy and 24.81±2.54 Gy in SEQ arm and 24.71±3.23 and 27.75±7.93 Gy in SIB arm respectively, p-values 0.75 and 0.07 (Table/Fig 8).

Discussion

The present prospective study evaluated and compared the acute toxicities and disease response between SEQ-VMATvs SIB-VMAT for HNSCC. To our best knowledge, this is the first randomised trial comparing SIB and SEQ boost using VMAT in non nasopharyngeal head and neck carcinoma. SEQ-VMAT and SIB-VMAT treatment in head and neck cancer are comparable in terms of overall response. Higher incidence of grade 1-2 acute dermatitis, mucositis and dysphagia was observed in SIB arm. No patient had treatment interruption due to acute toxicities. Toxicities were managed conservatively with use of topical anaesthetics, analgesics and opioids. Nutrition and hydration were maintained using dietician advised diet and i.v. fluids. There was no difference in the incidence of xerostomia and laryngeal toxicity. There was a trend towards higher incidence of grade 3 dysphagia in SIB arm but this was not found to be statistically significant. In present study, SEQ and SIB had comparable target coverage and dose to organs at risk. This was similar to the dosimetric studies done by Chen SW et al., and Nesrin D et al., comparing the target volume coverage and normal tissue sparing of SIB-IMRT versus SEQ-IMRT for nasopharyngeal carcinoma (18),(19).

In a single institutional retrospective study by Vlacich G et al., performed matched cohort analysis on patients of locally advanced head and neck carcinoma treated with chemoradiation to 69.3 Gy in 33 fractions (20). Out of 209 patients evaluated for analysis, 68 patients were treated with SEQ and 141 were treated with SIB. No significant difference was observed between SEQ versus SIB in disease free survival (63% vs 69%; p=0.27) and overall survival (69.3% vs 76.8%; p=0.13). They observed a significantly higher incidence of grade 3 or 4 acute dysphagia (82% vs 55%) and acute dermatitis (78% vs 58%), whereas present study shows no difference in the incidence of grade 3 dysphagia SEQ (11.5%) vs SIB (19.2%), p-value=0.44.

A randomised study by Songthong A et al., compared SEQ boost vs SIB IMRT in nasopharyngeal carcinoma on a total of 122 patients (21). Similar to the present study, this study showed no statistically significant difference in grade 3 mucositis, dysphagia and xerostomia. Also, there was no statistically significant difference in clinical response between SEQ-IMRT and SIB-IMRT in both the studies.

Scorsetti M et al., reported their early clinical experience in radiotherapy of different sites of head and neck cancer treated by volumetric modulated arcs (22). Similar to present study, percutaneous gastrostomy or feeding tube was not required in any of the patients. The most common acute grade 3 toxicities in this study were reported as mucositis (28%), dermatitis (14%) and dysphagia (7%). Whereas in present study, the most common grade 3 acute toxicities were mucositis (17%), dysphagia (15%) and laryngeal toxicity (6%). On sub-group analysis, patients treated with cetuximab had the majority of grade 3 toxicities, while the patients treated with cisplatin mainly had grade 1 toxicities. Whereas cisplatin was used as concurrent chemotherapy in all patients.

Jiang L et al., performed a meta-analysis of seven studies to compare the treatment outcome and severe acute side effects between SIB-IMRT and SEQ-IMRT (23). A total of 1049 patients were evaluated. This meta-analysis showed no significance difference in overall survival (Hazard Ratio, HR=0.94; 95% CI, 0.70-1.27; p-value=0.71), progression free survival (HR 1.03; 95% CI, 0.82-1.30; p-value=0.79), locoregional recurrence free survival (HR 0.98; 95% CI, 0.65-1.47; p-value=0.91) and distant metastasis free survival (HR 0.87; 95% CI, 0.50-1.53; p-value=0.63). Similarly, the present study shows no significant difference in the tumour response. The present study needs longer follow-up to compare overall survival and recurrence free survival.

In this study, SIB VMAT shows significantly higher incidence of acute dermatitis (grade1 dermatitis at two and four weeks; grade 2 dermatitis at six weeks) and acute mucositis (grade 1 mucositis at two weeks and grade 2 mucositis at four weeks) as compared to SEQ-VMAT. This difference in acute toxicities in SIB arm can be attributed to the higher dose per fraction to the high-risk volumes. SIB has an advantage of being convenient requires one plan as compared to two or more plans in SEQ. Simultaneous boost also reduces overall treatment duration. As the main aim of radiotherapy treatment is to provide the best tumour control in the target and non target lesions. Similar to other studies, in this study no significant difference was observed in the overall response to treatment. Both arms have equivalent dose prescription to the target volumes in terms of biological effective dose. Disease progression was observed in two patients in SIB arm and four in SEQ arm. No distant failure was seen in this study.

Limitation(s)

Lack of assessment of late toxicities, disease free survival and overall survival analysis because of short follow-up. Lack of blinding of the study participants and of the investigator was another limitation of this study.

Conclusion

For head and neck cancers, radical radiotherapy by SIB-VMAT and Sequential-VMAT planning are comparable in terms of overall response. But SIB arm had higher rates of acute dermatitis and mucositis. Dosimetric data was comparable between the two arms but SIB-VMAT was more convenient as no replanning was required as compared to SEQ-VMAT.

References

1.
Bray F, Ferlay J, Soerjomataram I, Siegel R, Torre L, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 2021. https://doi.org/10.3322/caac.21609). [crossref] [PubMed]
2.
Tuljapurkar V, Dhar H, Mishra A, Chakraborti S, Chaturvedi P, Pai PS. The Indian scenario of head and neck oncology- Challenging the dogmas. South Asian J Cancer. 2016;5(3):105-10. [crossref] [PubMed]
3.
Sweeney PJ, Haraf DJ, Vokes EE, Dougherty M, Weichselbaum RR. Radiation therapy in head and neck cancer: Indications and limitations. Semin Oncol. 1994;21(3):296-303. PMID: 8209262.
4.
Yeh S. Radiotherapy for head and neck cancer. Seminars in Plastic Surgery. 2010;24(02):127-36. [crossref] [PubMed]
5.
Teoh M, Clark C, Wood K, Whitaker S, Nisbet A. Volumetric modulated arc therapy: A review of current literature and clinical use in practice. The British Journal of Radiology. 2011;84(1007):967-96. [crossref] [PubMed]
6.
Verbakel WF, Cuijpers JP, Hoffmans D, Bieker M, Slotman BJ, Senan S. Volumetric intensity modulated arc therapy vs. conventional IMRT in head and neck cancer: A comparative planning and dosimetric study. Int J Radiat Oncol Biol Phys. 2009;74(1):252-59. [crossref] [PubMed]
7.
Vanetti E, Clivio A, Nicolini G, Fogliata A, Ghosh-Laskar S, Agarwal J, et al. Volumetric modulated arc radiotherapy for carcinomas of the oro-pharynx, hypo-pharynx and larynx: A treatment planning comparison with fixed field IMRT. Radiotherapy and Oncology. 2009;92(1):111-17. [crossref] [PubMed]
8.
Johnston M, Clifford S, Bromley R, Back M, Oliver L, Eade T. Volumetric-modulated arc therapy in head and neck radiotherapy: A planning comparison using simultaneous integrated boost for nasopharynx and oropharynx carcinoma. Clin Oncol (R Coll Radiol). 2011;23:503-11. Doi: 10.1016/j.clon.2011.02.002. [crossref] [PubMed]
9.
Studer G, Huguenin PU, Davis JB, Kunz G, Lütolf UM, Glanzmann C. IMRT using simultaneously integrated boost (SIB) in head and neck cancer patients. Radiat Oncol. 2006;1:7. Doi: 10.1186/1748-717X-1-7. [crossref]
10.
Jang S, Pyakuryal A, Cahlon O, Greenberg A, Tsai H, Lee S, et al. SU-E-T-595: A study of sequential and simultaneously integrated boost IMRT methods in head and neck cancer. Medical Physics. 2013;40(6Part20):342-42. [crossref]
11.
Orlandi E, Palazzi M, Pignoli E, Fallai C, Giostra A, Olmi P. Radiobiological basis and clinical results of the simultaneous integrated boost (SIB) in intensity modulated radiotherapy (IMRT) for head and neck cancer: A review. Critical Reviews in Oncology/Hematology. 2010;73(2):111-25. [crossref] [PubMed]
12.
Farzin M, Molls M, Astner S, Rondak I, Oechsner M. Simultaneous integrated vs. sequential boost in VMAT radiotherapy of high-grade gliomas. Strahlentherapie und Onkologie. 2015;191(12):945-52. [crossref] [PubMed]
13.
Guidelines With Evidence Blocks [Internet]. NCCN. 2021 [cited 9 November 2021]. Available from: https://www.nccn.org/guidelines/guidelines-with-evidence-blocks.
14.
AJCC Cancer Staging Handbook: TNM Classification of Malignant Tumors; SpringerLink; https://link.springer.com/book/9783319406176.
15.
The International Commission on Radiation Units and Measurements. Journal of the ICRU. 2010;10(1):Report 83. [crossref]
16.
Bentzen S, Constine L, Deasy J, Eisbruch A, Jackson A, Marks L, et al. Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC): An introduction to the scientific issues. Int J Radiat Oncol Biol Phys. 2010;76(3):S03-09. Doi: 10.1016/j.ejca.2008.10.026. [crossref] [PubMed]
17.
Eisenhauer E, Verweij J. New response evaluation criteria in solid tumors: RECIST GUIDELINE VERSION 1.1. European Journal of Cancer Supplements. 2009;7(2):5. [crossref]
18.
Chen SW, Yang SN, Liang JA, Shiau AC, Lin FJ. Comparative dosimetric study of two strategies of intensity-modulated radiotherapy in nasopharyngeal cancer. Med Dosim. 2005;30(4):219-27. [crossref] [PubMed]
19.
Nesrin D, Stephen K, Bahman E, Najeeb M, Nena M, Leonid BL, et al. Assessment of different IMRT boost delivery methods on target coverage and normal-tissue sparing. Int J Radiat Oncol Biol Phys. 2003;57(5):1480-91. [crossref]
20.
Vlacich G, Stavas M, Pendyala P, Chen S, Shyr Y, Cmelak A. A comparative analysis between sequential boost and integrated boost intensity-modulated radiation therapy with concurrent chemotherapy for locally-advanced head and neck cancer. Radiation Oncology. 2017;12(1):13. Doi: 10.1186/s13014-016-0756-x. [crossref] [PubMed]
21.
Songthong A, Kannarunimit D, Chakkabat C, Lertbutsayanukul C. A randomised phase II/III study of adverse events between sequential (SEQ) versus simultaneous integrated boost (SIB) intensity modulated radiation therapy (IMRT) in nasopharyngeal carcinoma; preliminary result on acute adverse events. Radiation Oncology. 2015;10(1);166: Doi: 10.1186/s13014-015-0472-y. [crossref] [PubMed]
22.
Scorsetti M, Fogliata A, Castiglioni S, Bressi C, Bignardi M, Navarria P, et al. Early clinical experience with volumetric modulated arc therapy in head and neck cancer patients. Radiation Oncology. 2010;5(1):93. https://doi.org/10.1186/1748-717X-5-93. [crossref] [PubMed]
23.
Jiang L, Zhang Y, Yang Z, Liang F, Wu J, Wang R. A comparison of clinical outcomes between simultaneous integrated boost (SIB) versus sequential boost (SEQ) intensity modulated radiation therapy (IMRT) for head and neck cancer: A meta-analysis. Medicine (Baltimore). 2019;98(34):e16942. [crossref] [PubMed]

DOI and Others

DOI: 10.7860/JCDR/2022/50041.16076

Date of Submission: Apr 25, 2021
Date of Peer Review: Jun 01, 2021
Date of Acceptance: Jan 06, 2022
Date of Publishing: Mar 01, 2022

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. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Apr 26, 2021
• Manual Googling: May 27, 2021
• iThenticate Software: Jan 06, 2022 (14%)

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