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

Users Online : 37496

AbstractMaterial and MethodsResultsDiscussionConclusionAcknowledgementReferencesDOI and Others
Article in PDF How to Cite Citation Manager Readers' Comments (0) Audio Visual Article Statistics Link to PUBMED Print this Article Send to a Friend
Advertisers Access Statistics Resources

Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"

Dr Mohan Z Mani,
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
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,
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,
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
(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)
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.
On April 2011

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
On Jan 2020

Important Notice

Original article / research
Year : 2022 | Month : May | Volume : 16 | Issue : 5 | Page : EC07 - EC10 Full Version

Prognostic Role of CRS in High Grade Serous Ovarian Tumour Patients Receiving Neoadjuvant Chemotherapy in a Tertiary Care Hospital of Central India

Published: May 1, 2022 | DOI:
Manal Ashraf Ali, Naila Durrani, Khaneta Parveen, Zeeshanuddin Ahmad, Farah Jalaly Meenai

1. Associate Professor, Department of Pathology, Chirayu Medical College and Hospital, Bhopal, Madhya Pradesh, India. 2. Associate Professor, Department of Pathology, Chirayu Medical College and Hospital, Bhopal, Madhya Pradesh, India. 3. Associate Professor, Department of Pathology, Chirayu Medical College and Hospital, Bhopal, Madhya Pradesh, India. 4. Associate Professor, Department of Oncosurgery, Chirayu Medical College and Hospital, Bhopal, Madhya Pradesh, India. 5. Professor, Department of Pathology, Chirayu Medical College and Hospital, Bhopal, Madhya Pradesh, India.

Correspondence Address :
Dr. Manal Ashraf Ali,
103, C Block, Doctor Quarters, Chirayu Medical College and Hospital,
Bairagarh, Bhopal, Madhya Pradesh, India.


Introduction: Ovarian tumours are rarely diagnosed early, patients presents only when the abdominal mass is appreciable in size. The current mode of treatment involves neoadjuvant chemotherapy with interval debulking surgery, followed by completion of the chemotherapy. The pathological examination of the interval debulking specimen allows an evaluation of the extent of the response to the chemotherapy and sensitivity of the tumour to the same. The Chemotherapy Response Score (CRS) developed by Bohm S et al., is being used to predict the prognosis of these patients. The advent of molecular genetics has allowed us to categorise tumours as per the mutations they possess, the prominent in High Grade Serous Carcinoma (HGSC) being TP53, BRCA1/2 and Homologous Recombination Deficiency (HRD). This knowledge is used to cater to the specific therapeutic needs of the patients.

Aim: To apply the CRS to cases of high grade serous carcinomas of the ovary, presenting to the centre and association of the score with their survival.

Materials and Methods: A total of 30 patients of high grade serous carcinoma of ovary who received neoadjuvant chemotherapy and had interval debulking surgery were included in the study. The histopathological examination of the resected specimen was done with special emphasis on the omental deposits and the degree of necrosis, fibrosis, inflammation, macrophages and residual tumour. Chi square statistics with p-value association of was done, to establish significance.

Results: The histological parameters of necrosis, chronic inflammation and residual tumour in the omental deposits were found to be the most significant in association of to the CRS scores. Also, the CRS grading was associated with the survival of the patients.

Conclusion: The CRS was found to associate well with the survival of the patients. This study recommends that CRS score be done in all post NACT high grade serous ovarian tumours, which will guide further treatment.


Chemotherapy response score, Debulking surgery, Ovarian cancer

After cervical cancer, ovarian cancer is the second most common gynaecological malignancy in western countries and is responsible for the most mortality amongst them (1). The new 2020 World Health Organisation (WHO) classification of ovarian cancers takes into account morphology, immune-profile and molecular profiles. On the basis of this there are five main epithelial carcinomas: high and low grade serous carcinoma, endometroid carcinoma, clear cell carcinoma and mucinous carcinoma. Majority of advanced stage ovarian cancers are represented by high grade serous carcinoma (70%) and are the most lethal (2).

The treatment protocols for advanced stage ovarian cancer have changed over the years from the initial approach of primary surgical resection followed by post operative chemotherapy, to primary Neoadjuvant Chemotherapy (NACT) for cytoreduction followed by debulking. International Federation of Gynecology and Obstetrics (FIGO) stage III/IV ovarian cancers are now started with platinum-based cycles of chemotherapy to reduce the tumour bulk, with interval debulking and followed by completion of cycles of chemotherapy. National Comprehensive Cancer Network (NCCN) guidelines for 2012 recommended this approach to reduce morbidity associated with surgery (3).

The tumour response to NACT is assessed on the histopathological examination of interval debulking specimens and thus guides the treatment. Bohm S et al., developed a histopathologic scoring system for measuring response to NACT in interval debulking surgery specimens of stage IIIC to IV tubo-ovarian high grade serous carcinoma, called CRS (4). This scoring system has still not found its place in the routine oncology reporting in India. In this study implementation of the CRS in the Indian scenario was approached and its association with the prognosis, as measured by the disease free survival of the patients who have undergone interval debulking post NACT, at our centre.

Material and Methods

This was a retrospective and prospective study conducted in a tertiary care hospital of 30 cases of high grade serous ovarian cancers, who presented over a period of three years (January 2018-December 2020). Approval for the study was taken from the Institutional Ethics Committee (IEC) IEC no. CMCH/EC/2022/04-12.

Inclusion criteria: Patients with ovarian malignant tumours who received initial chemotherapy and then had interval debulking surgery, and were on follow-up were included in the study.

Exclusion criteria: a) Patients with tumours other than high grade serous carcinoma of the ovary, b) Patients of serous carcinoma of the ovary who did not receive chemotherapy before surgery were excluded from the surgery, c) patients who were lost to follow-up were excluded from surgery.

Sample size: All the cases during the stated study time period were included i.e. 30 cases were included as per the, inclusion and criteria stated above.

Study procedure: Patients were diagnosed on the basis of ultrasonography findings of enlarged ovaries with solid and cystic component, raised Cancer (CA) 125 and or positive effusion cytology. These patients were given initial four cycles of platinum-based chemotherapy, comprising paclitaxel and carboplatin. This was followed by interval debulking surgery after which the histopathological examination was done and the rest of the chemotherapy cycles were completed.

Surgical specimens received included total hysterectomy with regional lymph node dissection and omentum for staging. Specimens were grossed, and sections were stained with Haematoxylin and Eosin (H&E). Two experienced pathologists reviewed the sections, with emphasis on residual tumour, fibrosis, necrosis, inflammation, calcification, macrophages and omental and extraovarian deposits. These histological parameters have been graded as <50% and ≥50% of entire tissue on the most representative H&E section for that parameter. Calcification and metastatic deposits were graded as present or absent. The chemotherapy response scoring was done as per the three-tier CRS system proposed by Bohm S et al., in 2015, and incorporated in the dataset of Royal College of Pathologists (Table/Fig 1) (4),(5). An association between the CRS scores and the post-operative period follow-up of the patients was done, including the recurrences, death and disease-free survival of the patients.

Statistical Analysis

The statistical analysis was performed using IBM Statistical Package for the Social Sciences (SPSS) software version 23.0. Pearson Chi–square test was used to analyse the Histopathological parameters with Chemotherapy response score. The p-value <0.05 was considered as statistically significant.


The 30 cases of advanced stage ovarian cancers who underwent interval debulking surgery post NACT included in the study ranged in age from 41-70 years, with a mean age of 51 years and 8 months. The median age was 51 yrs, 20% of the cases belonged to 41-45 years of age, 16.67% cases belonged to 46-50 yrs of age. 23.33% belonged to 51-55years of age. 26.67% were in the 56-60 years age group, 6.66% were in the 61-65 and 66-70 years age group each. 66.6% of the patients had disease involving bilateral ovaries, and of the rest, 26.8% involved only the left and 6.6% involved the right ovary. Eight patients had positive ascitic fluid cytology; these patients had bilateral disease with capsular breech of the ovaries. These cases also had high grade residual tumour post NACT thus showing minimal response to the chemotherapy regimen.

The degree of fibrosis was inversely proportional to the residual tumour burden. Patients with the highest degree of fibrosis, were the ones with lesser or no residual viable tumour. However, the p value was 0.9, which was >0.05 and thus was not statistically significant when compared with the CRS scoring (Table/Fig 2).

The cases with the greater tumour burden also showed more extensive necrosis. Necrosis was noted in the ovaries, lymph nodes and omentum. Patients with moderate necrosis of the omental deposits had a better CRS scoring and prognosis; as compared to those with greater necrosis with a p-value of 0.0368 ((Table/Fig 2)). Thus, the necrosis bears a significant association with the CRS and hence with prognosis.

Foamy macrophages were seen when the tumour burden was more, and were less with less viable tumour. However, on comparison with the CRS, the p-value is 0.067, (p<0.05) this was not significant (Table/Fig 2). The inflammatory response was represented by the lymphocytic infiltrate. More infiltrate was seen when there was greater tumour burden, and decreased with response to the chemotherapy. The amount of infiltrate was compared to the CRS and the corresponding p-value was 0.022 and thus significant (Table/Fig 2).

The patients with the maximum residual tumours in the omental deposits were representative of those having least response to the chemotherapy and were thus given the score of CRS 1 (Table/Fig 3). Absence of viable residual tumour in omentum was CRS3 and those with identifiable tumour response was CRS 2 (Table/Fig 4). On statistical analysis, the p-value comes to be 0.03415 and was hence significant (Table/Fig 2).

Calcification represented by psammoma bodies was more in the patients showing a better response and having a lesser tumour burden and coincided with a longer disease free interval.

The patients were followed-up for two months to 42 months post surgery. There were deaths in three cases, all of whom were CRS 1 (Table/Fig 5). The first had bilateral disease and >50% residual tumour, she presented within three months of surgery with metastasis in liver and expired in six months. The second case was also of bilateral disease with capsular breech and deposits in omentum and mesentery, she presented with pleural effusion and lung metastasis within eight months of surgery and died five months later. The third patient presented at 11 months with massive ascitic effusion and multiple omental metastasis, and did not survive another month.

Four cases relapsed within 12 months of surgery, of these two were CRS 1 and two were CRS 2; they presented with malignant ascites and raised CA125. Four cases relapsed after a year, two cases were CRS 2 and a single case each of CRS 1 and CRS 3. Other cases were free of disease, for a period upto 42 months.

In our study the CRS corresponded well with the disease-free survival period. CRS 3 cases showed a single recurrence i.e., 7.1% (01/14) in their follow-ups and 92.9% were disease free in the follow-up period (Table/Fig 5). Amongst the CRS 2 cases, 85.71% (6/7) had recurrence of disease and 42.85% (3/7) of these patients expired. Only one CRS 1 patient had no recurrence till follow-up. The intermediate CRS 2 cases 55.6% (5/9) had no recurrence and 44.4% (4/9) came back with recurrence, but there were no deaths reported (Table/Fig 5).


The post chemotherapy changes in breast cancers, colon, osteosarcomas etc have been documented and used as prognostic indicators. In 2015 Bohm S et al., introduced CRS for post NACT morphological changes in the omentum in high grade ovarian cancers, and proved its reproducibility and prognostic significance (4). The International Collaboration on Cancer Reporting (ICCR) had recommended the implementation of the CRS and this has been incorporated in the dataset for reporting of tumours of ovaries, fallopian tubes and peritoneum, by the Royal College of Pathologists in 2019 (5).

The diagnosis of ovarian tumours is still indirect and based on radiology, raised CA125 levels and malignant cells in ascitic fluid. The absence of primary biopsy sampling comprises the primary categorisation and grading of tumours. Thus, the interpretation of response to the drug regimen and further treatment plan is almost entirely dependent on the post NACT histopathology report.

Before Bohm S et al., gave their CRS on the study of omental deposits of ovarian tumours, McCluggage WG et al., and Sassen S et al., tried to assess the tumour regression in ovaries post NACT (6),(7). In 2012 Samrao D et al., in their study attempted to use the histological findings in ovaries in post NACT cases as indicators of predictive outcome of the disease (8). Singh P et al., (9) and Ditzel HM et al., (10) carried forward the studies on omental CRS and both agreed with the longer disease-free survival of CRS 3 patients as stated by Bohm S et al., (4). However, Singh P et al., noted that this association was not significant after controlling for debulking status (9).

All the cases of CRS 3, except one had no evidence of recurrence of disease till the follow-up period. Cases of CRS 1 score representing almost no or minimal response to treatment, came back with recurrence of disease ((Table/Fig 5)). These findings collaborate the seminal paper of Bohm S et al., (4) and are in tandem with those of Singh P et al., (9) and Ditzel HM et al., (10).

Present study shows a significant statistical association with residual tumour, degree of necrosis and lymphocytic infiltrate and the CRS (Table/Fig 2). The dystrophic calcification seen as psammomatous bodies was also associated with longer disease free survival, this concurs with the study of McCluggage WG et al., (6). A comparison of the findings of the present study in the Indian scenario with that of Cohen PA et al., (11), Singh P et al., (9) and Ditzel HM et al., (10) support and reiterate the findings of Bohm S et al., (4), with respect to the prognosis of patients as per the CRS. The CRS 3 patients in all the above studies with minimal tumour or a complete response have fared well with longer disease-free periods as compared to the CRS 1 and 2 patients (Table/Fig 6).

All high grade serous ovarian carcinomas do not necessarily respond to the current regimens, hence, the importance of interval debulking and histopathological examination. This mid-therapy evaluation is extremely helpful for guiding further treatment. The non responders can then be offered other chemotherapeutic agents to which their tumour may be sensitive. This was done by Masuda N et al., when they offered capecitabine to breast carcinoma patients, who had NACT resistant tumours; and they then had better outcomes (12). Ivantsov AO has pointed out that tumors may change their molecular properties during treatment, thus, making an initially chemosensitive tumour a chemoresistant one (13). HGSC are known to arise from Serous Tubal Intraepithelial Carcinoma (STIC) at the fimbrial end of the fallopian tube, and hence have now been called tubo-ovarian high grade serous carcinomas in the fifth edition of the WHO Classification of Female Genital Tumours (14). HGSCs are associated with TP53 mutations (more than 97%) and HRD including BRCA mutations, while LGSCs are characterised by BRAF or KRAS mutations.(2) BRCA1 or BRCA2 mutations have a 30-70% higher risk of the women developing HGSC by age of 70 (15),(16). PARP inhibitors have been included as a standard of care for HGSC (17). However non-HRD tumours do not respond to PARP inhibitors, testifying to the heterologous nature of HGSCs (18). Cohen PA et al., in their systemic review and meta-analysis also make a point towards personalised treatment on the basis of CRS stratification (11). This makes the examination and accessibility to tissue for further cytogenetic studies most important.


This study was limited by the small sample size, as patients were lost to follow-up, and not all agree to NACT and opt for direct surgery citing monetary reasons.


This study supports the findings of the paper by Bohm S et al., that the CRS from the omental grading corresponds with the disease-free survival of the patients. All the patients with CRS 3 score were disease free, post-surgery and NACT, except one. The CRS 1 and 2 patients had shorter disease free interval and poor prognosis. The wider implementation in the Indian scenario of the CRS score will help in prognosis of patients. Also, the molecular analysis of the CRS 1 and CRS 2 tumours will give the patients and clinicians the option to change their chemotherapy regime based on the profile of their tumours, and hence the means to a better outcome.


The authors would like to thank Dr. Sachin Gupta (MD,PSM) for his
help in the statistical analysis.


Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):07-33. [crossref] [PubMed]
De Leo A, Santini D, Ceccarelli C, Santandrea G, Palicelli A, Acquaviva G, et al. What is new on ovarian carcinoma: Integrated morphologic and molecular analysis following the New 2020 World Health Organization Classification of Female Genital Tumors. Diagnostics (Basel). 2021;11(4):697. [crossref] [PubMed]
Morgan RJ Jr, Alvarez RD, Armstrong DK, Burger RA, Castells M, Chen LM, et al. Ovarian cancer, version 3.2012. J Natl Compr Canc Netw. 2012;10(11):1339-49. Doi: 10.6004/jnccn.2012.0140. PMID: 23138163. [crossref] [PubMed]
Böhm S, Faruqi A, Said I, Lockley M, Brockbank E, Jeyarajah A, et al. Chemotherapy response score: Development and validation of a system to quantify histopathologic response to neoadjuvant chemotherapy in tubo-ovarian high-grade serous carcinoma. J Clin Oncol. 2015;33:2457-63. [crossref] [PubMed]
Wilkinson N, Vroobel K, McCluggage WG. Dataset for histopathological reporting of carcinomas and borderline tumours of the ovaries, fallopian tubes and peritoneum. Standards and datasets for reporting cancers. G079. The Royal College of Pathologists. July 2019.
McCluggage WG, Lyness RW, Atkinson RJ, Dobbs SP, Harley I, McClelland HR, et al. Morphological effects of chemotherapy on ovarian carcinomas. J Clin Pathol. 2002;55:27-31. [crossref] [PubMed]
Sassen S, Schmalfeldt B, Avril N, Kuhn W, Busch R, Hofler H. Histopathologic assessment of tumour regression after neoadjuvant chemotherapy in advanced stage ovarian cancer. Hum Pathol. 2007;38 (6):926-34. [crossref] [PubMed]
Samrao D, Wang D, Ough F. Histologic parameters predictive of disease outcome in women with advanced stage ovarian carcinoma treated with neoadjuvant chemotherapy. Transl Oncol. 2012;5:469-74. [crossref] [PubMed]
Singh P, Kaushal V, Rai B, Rajwanshi A, Gupta N, Dey P, et al. The chemotherapy response score is a useful histological predictor of prognosis in high-grade serous carcinoma. Histopathology. 2018;72:619-25. [crossref] [PubMed]
Ditzel HM, Strickland KC, Meserve EE, Stover E, Konstantinopoulos PA, Matulonis UA, et al. Assessment of a Chemotherapy Response Score (CRS) system for tubo-ovarian High-Grade Serous Carcinoma (HGSC). Int J Gynecol Pathol. 2019;38(3):230-40. [crossref] [PubMed]
Cohen PA, Powell A, Böhm S, Gilks CB, Stewart CJR, Meniawy TM, et al. Pathological chemotherapy response score is prognostic in tubo-ovarian highgrade serous carcinoma: A systematic review and meta-analysis of individual patient data. Gynecol Oncol. 2019;154(2):441-48. [crossref] [PubMed]
Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med. 2017;376:2147-59. [crossref] [PubMed]
Ivantsov AO. Pathological response of ovarian cancer to neoadjuvant chemotherapy. Chin Clin Oncol. 2018;7(6):59. [crossref] [PubMed]
WHO. Classification of Tumours Editorial Board. In Female Genital Tumours, 5th ed.; International Agency for Research on Cancer: Lyon, France, 2020.
Folkins AK, Longacre TA. Hereditary gynaecological malignancies: Advances in screening and treatment. Histopathology. 2013;62(1):02-30. [crossref] [PubMed]
Girolimetti G, Perrone AM, Santini D, Barbieri E, Guerra F, Ferrari S, et al. BRCAassociated ovarian cancer: From molecular genetics to risk management. Biomed Res Int. 2014;2014:787143. [crossref] [PubMed]
Lord CJ, Ashworth A. PARP inhibitors: Synthetic lethality in the clinic. Science. 2017;355(6330):1152-58. [crossref] [PubMed]
Etemadmoghadam D, deFazio A, Beroukhim R, Mermel C, George J, Getz G, et al. Integrated genome-wide DNA copy number and expression analysis identifies distinct mechanisms of primary chemoresistance in ovarian carcinomas. Clin. Cancer Res. 2009;15(4):1417-27. [crossref] [PubMed]

DOI and Others

DOI: 10.7860/JCDR/2022/56069.16299

Date of Submission: Mar 05, 2022
Date of Peer Review: Mar 24, 2022
Date of Acceptance: Apr 01, 2022
Date of Publishing: May 01, 2022

• 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? No
• For any images presented appropriate consent has been obtained from the subjects. No

• Plagiarism X-checker: Mar 11, 2022
• Manual Googling: Mar 25, 2022
• iThenticate Software: Mar 28, 2022 (4%)

ETYMOLOGY: Author Origin

JCDR is now Monthly and more widely Indexed .
  • Emerging Sources Citation Index (Web of Science, thomsonreuters)
  • Index Copernicus ICV 2017: 134.54
  • Academic Search Complete Database
  • Directory of Open Access Journals (DOAJ)
  • Embase
  • EBSCOhost
  • Google Scholar
  • HINARI Access to Research in Health Programme
  • Indian Science Abstracts (ISA)
  • Journal seek Database
  • Google
  • Popline (reproductive health literature)