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    -  Palled SR
    -  Venugopal BK
    -  Nihanthy D S
    -  Khanum H
    -  Vijay C R
    -  Viswanath L
    -  Ramachandra C

 
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ORIGINAL ARTICLE
Ahead of print publication
 

Clinical profile and outcomes in cervical cancer: An audit from a tertiary cancer center


1 Department of Radiotherapy, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
2 Department of Statistics, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
3 Department of Surgical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India

Date of Submission09-Mar-2019
Date of Decision30-Nov-2019
Date of Acceptance04-Dec-2019
Date of Web Publication05-Sep-2022

Correspondence Address:
Bindu K Venugopal,
Department of Radiotherapy, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijc.IJC_211_19

  Abstract 


Background: Carcinoma cervix contributes to a major proportion of cancer treatment in tertiary oncology centers. The outcomes are dependent on multiple factors. We conducted an audit to establish the pattern of treatment practiced for carcinoma cervix at the institute and suggest changes thereof to improve the quality of care.
Methodology: A retrospective observational study of 306 diagnosed cases of carcinoma cervix was carried out for the year 2010. Data was collected with regards to diagnosis, treatment, and follow-up. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 20.
Results: Out of 306 cases, 102 (33.33%) patients received only radiation therapy and 204 (66.66%) patients received concurrent chemotherapy. The most common chemotherapy used was weekly cisplatin 99 (48.52%), followed by weekly carboplatin 60 (29.41%) and three weekly cisplatin 45 (22.05%). Disease-free survival (DFS) at 5 years was 36.6% with patients of overall treatment time (OTT) of <8 weeks and >8 weeks showing DFS of 41.8% and 34% (P = 0.149), respectively. Overall survival (OS) was 34%. Concurrent chemoradiation improved overall survival by a median of 8 months (P = 0.035). There was a trend towards improved survival with three weekly cisplatin regimen, however, insignificant. Stage correlated with improved overall survival significantly with stage I and II showing 40% and stage III and IV showing 32% (P < 0.05) OS. Acute toxicity (grade I-III) was higher in the concurrent chemoradiation group (P < 0.05).
Conclusion: This audit was a first of its kind in the institute and threw light on the treatment and survival trends. It also revealed the number of patients lost to follow-up and prompted us to review the reasons for it. It has laid the foundation for future audits and recognized the importance of electronic medical records in the maintenance of data.


Keywords: Carcinoma cervix, chemoradiation, clinical audit, radiotherapy
Key Message: The importance of documentation in oncology practice cannot be emphasized enough. Through this audit we were able to gather vital information regarding prevalent practices which would otherwise be missed. Formal clinical trials have become increasingly difficult; taking a longer time to design, acrue, execute and analyze. Data collected from various centers practicing patient-oriented customised medicine will form the basis for directing practices in the future. The purpose of this audit was to contribute our two cents to that large volume of data.



How to cite this URL:
Palled SR, Venugopal BK, Nihanthy D S, Khanum H, Vijay C R, Viswanath L, Ramachandra C. Clinical profile and outcomes in cervical cancer: An audit from a tertiary cancer center. Indian J Cancer [Epub ahead of print] [cited 2022 Sep 28]. Available from: https://www.indianjcancer.com/preprintarticle.asp?id=355615





  Introduction Top


Carcinoma cervix is one of the most common malignancies of the genitourinary tract in India.[1] Carcinoma cervix has the potential to spread loco-regionally to the parametrium, uterus, bladder, rectum, and pelvic nodes.[2] Late stages also metastasize to the bone, lungs, and brain. It is the most common cancer detected in the female population in Karnataka based on the hospital and population-based cancer registry. The total number of registered cancer patients in the year 2010 was more than 15,000.[3] The diagnosis of cancer was made in 9735 patients, out of which 695 were of cervical cancer. The national cancer registry program shows that cervical cancer contributes to 15.7% of all cancer cases.[4]

Chemoradiation is the principal modality of treatment through all the stages. Early stages are treated primarily with surgery with or without chemoradiation.

There are a few audits and outcomes reported from the South of India although there are reports from other parts of the country.[5] This study was conducted to assess the trends in treatment and survival at the center and give a direction to future audits and patient care with the data obtained. The audits reported previously have addressed the workflow and standards followed in a particular department. There are some audits which have also reported on outcomes.[6] Our intention was to report on both since we wanted to assess the effect of the protocols followed and suggest alterations accordingly.

Kidwai Memorial Institute of Oncology (KMIO) is a regional cancer center in Bengaluru, Karnataka with one linear accelerator and three telecobalt units at the time of the study. Presently, it houses seven linear accelerators and two telecobalt units with one being decommissioned. KMIO has a low-dose-rate (LDR) brachytherapy with Cesium-137 source and a high-dose-rate (HDR) brachytherapy with Iridium-192.


  Aim of the Study Top


The primary aim of the study is to establish the pattern of treatment practiced, and to suggest changes based on the current standards of practice. We aimed to record the type of radiation and concurrent chemotherapy treatment delivered. The toxicity profile and survival data in our institute were recorded additionally. This would help us institute changes in existing practice and improve outcomes for our patients.

Criteria and standards

Patients were staged based on International Federation of Gynecology and Obstetrics staging suggested by American Joint Committee on Cancer (AJCC) 7th edition manual.[7] They were treated based on the recommendations by National Comprehensive Cancer Network (NCCN) guidelines (2009) and National Cancer Institute (NCI) guidelines for cervical cancer 2009.[8]

The standard of care for cervical cancer beyond and including stage I is concurrent chemoradiation,[9],[10] followed by brachytherapy to an equivalent dose of 80–90 Gy to point A.


  Methods Top


Institutional Review Board clearance was obtained for the study. All cervical cancer patients registered between the ages of 25–85 years at the center from 1st January 2010 to 31st December 2010 were included in the study. Case files of patients with a diagnosis of carcinoma cervix, which were registered directly or were referred to the department of radiation oncology, were collected from the medical records department. The patients were followed up for a period of 6 years and the survival and toxicity data was collected in the year 2016. The data was collected in a data collection form and tabulated in Microsoft excel sheet and statistical analysis with IBM SPSS version 20 was carried out. Survival was analyzed with Kaplan-Meier distribution and statistical significance of treatment and toxicities with Chi-square test.

The criteria used for diagnosis included clinical examination, histopathology report, chest X-ray, ultrasound of abdomen and pelvis, cystoscopy, and proctoscopy where indicated and staged according to the International Federation of Gynecology and Obstetrics (FIGO). The patients included in the study had external beam radiation on telecobalt by two-dimensional technique or on the linear accelerator by three-dimensional technique, with or without concurrent chemotherapy with platinum compounds. The regimen of chemotherapy included was weekly or three weekly administration of cisplatin or carboplatin.[10] The regimen of chemotherapy was decided at the discretion of the treating doctor. Patients excluded from the study were postoperative patients who could not be staged and patients with metastatic disease. Some patients did not receive concurrent chemotherapy on account of the expense and in some patients, the reasons were not documented.

Dose delivered by external beam radiation therapy was 45–50.4 Gy at 1.8–2 Gy per fraction. A two-field technique or four-field technique was used for patients treated on telecobalt. The upper border was at the L4-5 vertebral junction and lower border at the bottom of the obturator foramen or lower, depending upon the vaginal extent.[11] Inguinal nodes were treated if indicated. The lateral border was 1.5–2 cm lateral to the pelvic inlet. When three dimensional planning was carried out, the patients underwent a planning Computed Tomography (CT) with full bladder and contoured for gross tumor volume (which includes clinically assessed palpable disease and radiologically demarcated enhancing gross tumor), clinical tumor volume (which includes microscopic disease), and planning tumor volume (which includes margins for setup error) according to the International Commission on Radiation Units and Measurements (ICRU) 62 recommendations[12] and Radiotherapy and Oncology Group (RTOG) guidelines for contouring carcinoma cervix.[13]

Brachytherapy 25–30 Gy equivalent was received by all patients following external beam radiation treatment. 25–30 Gy to point A by LDR and 7 Gy in 3 fractions to point A by HDR using Fletcher suit applicators for intracavitary brachytherapy (ICBT) and Syed Neblett template for interstitial brachytherapy (ISBT). In postoperative cases, 30 Gy was prescribed to the surface or at 0.5 cm from the surface of the vaginal mucosa.


  Results Top


The total number of carcinoma cervix cases in the department were 695. The medical records analyzed were 306. The remaining patients were referred to tertiary cancer facilities nearest to them.

The median age of the patients was 49 (range = 18-85) years and the median follow-up was 18.5 (range = 0-70) months. The distribution of patients based on stage is shown in [Table 1]. There were two IIA patients and one IIIA patient. Stage IV includes stage IVA. Metastatic patients were excluded from the study. In view of small numbers of these substages, they were grouped together in stage II, III, and IV. Majority of the patients presented in locally advanced stages with stage III and IV contributing to 192 (62.74%) of the total number of patients. The histological distribution is shown in [Table 1]. 286 (93.46%) of the patients had squamous cell histology. Almost all patients underwent some form of imaging, ultrasound of the abdomen and pelvis in 92.8% and contrast-enhanced CT scan in 7.2% of them.
Table 1: Disease characteristics

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Radiation therapy (RT) alone was received by 102 (33.33%) patients, whereas concurrent chemoradiation (CTRT) was received by 204 (66.66%) patients [Table 2]. Many patients did not receive chemotherapy due to economic reasons. The center was in transition from two-dimensional to three-dimensional radiotherapy planning. Hence, 285 (93.1%) of the patients were treated on telecobalt and the rest 21 (6.86%) on linear accelerator by 3DCRT technique. Platinum compounds were used as concurrent chemotherapy. Weekly cisplatin 40 mg/m2, carboplatin weekly with area under the curve (AUC) 2, and three weekly regimen of cisplatin 100 mg/m2 were administered with external beam radiation [Table 2]. Most of the patients (n = 298) underwent low-dose-rate brachytherapy treatment with manual after loading. The range of patient follow-up was from 1 month to 7 years. The median overall treatment time (OTT) was 60 days with a range of 40–135 days.
Table 2: Details of the treatment received

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The disease-free survival (DFS) was 36.6% at the end of 5 years. The DFS of patients with OTT of less than 8 weeks and more than 8 weeks was 41.8% and 34%, respectively, (P = 0.149) which did not reach statistical significance. Overall survival, defined as the survival of the patients from the date of diagnosis to the last date of follow-up, up to 6 years was 34%. Patients receiving RT only and CTRT had overall survival (OS) of 29% and 36%, respectively. The addition of chemotherapy to RT increased the median survival by 8 months and was significant (P = 0.035) [Figure 1]. There was a trend toward improved survival with three weekly cisplatin [Figure 2] though not significant. The survival fraction was significantly better with the lower staging of the disease. Stage I and II showing 40% versus stage III and IV showing 32% survival (P < 0.05) [Figure 3].
Figure 1: This Kaplan-Meier distribution shows the survival of patients treated with radiation therapy alone (in blue) versus concurrent chemoradiation (in green). The OS was significantly better in patients treated in the latter arm

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Figure 2: This is a Kaplan-Meier (KM) curve showing the distribution of patients treated with three weekly cisplatin (in green) versus weekly cisplatin (in blue)

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Figure 3: This Kaplan-Meier survival curve shows the significance of stage in survival

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Acute toxicity according to the RTOG grading system is indicated in [Table 3]. Hematological, gastrointestinal, genitourinary, and skin toxicity were all significantly more in the CTRT group of patients. Acute grade III hematologic toxicity was significant in CTRT arm versus RT alone (10% versus 0%). Late toxicities analyzed were mostly gastrointestinal in terms of frequency of diarrhea, blood in stools, and skin toxicity which was assessed by skin atrophy, telangiectasia, and edema. The gastrointestinal and skin toxicity remained similar between the two groups. Late grade III gastrointestinal toxicities were seen only in two patients in CTRT arm. There were no grade IV toxicities reported. Vaginal toxicity was not recorded.
Table 3: Acute and late grade I and II toxicities in the RT only and RT+CT patients

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Areas of good practice

All the patients were clinically examined and staged according to FIGO staging. All patients of carcinoma cervix underwent radiation therapy to the recommended doses. Two-thirds of the patients received concurrent chemotherapy. All patients received brachytherapy within reasonable overall treatment times. Patterns of care studies in carcinoma cervix have shown brachytherapy to be an integral part of disease-free survival.[14]

Areas requiring improvement

Maintenance of medical records using an electronic medical record system will help in data collection, analysis of data, and improve follow-up of patients. CT scan/Magnetic Resonance Imaging may be used to obtain more information about the disease extension. Although it was not recommended by FIGO in the 7th edition of AJCC staging, the increasing use of image guidance for treatment planning and brachytherapy has made it preferable. More number of patients should be enrolled for concurrent chemotherapy. Patients should be recruited for image-guided brachytherapy. 3DCRT remains the minimum standard of care worldwide and should be adopted in a tertiary cancer center for all patients. It was recognized that many patients were lost to follow-up. The reasons for losing communication with the patients should be analyzed and rectified.

Lessons learnt

Concurrent chemoradiation is a well-established standard of care for carcinoma cervix. This audit confirmed the findings of international studies and meta-analysis that chemotherapy given along with radiation contributes to overall survival.[9],[10]

The trend of three weekly cisplatin giving better results, albeit non-significant statistically, was identified. The toxicities reported were predictable and on par with what has been reported in the literature.[15]

This audit also revealed some pitfalls in the system; time from diagnosis to treatment was not recorded. This contributes to treatment delay. The factors affecting the same including caseload burden, prolonged waiting time, and patient factors were not considered. Imaging patients with CT/MRI and treating them with conformal techniques is the order of the day. Further audits should focus on this. The reasons for not enrolling patients in chemotherapy should be studied and the number of chemotherapy cycles given should also be optimized. Toxicities in the subacute and chronic period will help us in tailoring treatment further. The follow-up of patients post-treatment was not satisfactory. There should be a follow-up policy in place and facilities to refer and record follow-up data for patients who are from distant places. Owing to long travel times and peripheral distribution of patient population, correspondence by written or telephonic means was often met with no response.

Future policies for the institute

Insufficient follow-up data contributes to significant data loss. Future policies need to concentrate on why many patients were lost to follow-up and devise a method to track them, for example, using universal health cards, interlinking them and facilitating follow-up at nearby tertiary cancer centers. One way of keeping a tab on patient information is to maintain a directory of contact information. In the modern day, with widespread usage of mobile phones, reaching patients remotely to either collect or dissipate The overall survival reported in literature for carcinoma cervix is 40%-52%.[9] With the limited follow-up data, it is important to scrutinize why the OS in our patient population is not close to that reported internationally. Some of the factors to be accounted for include advanced disease at presentation (62% of patients were in stage III and IV), duration between time to diagnosis and time to treatment, reasons for prolonged overall treatment time (OTT),[16] additional comorbidities, anemia and, hypoproteinemia. Conformal techniques are the present minimum requirement in radiation therapy, even without dose modulation. Almost all centers are being upgraded with these techniques and telecobalt machines are being phased out in favor of them. Hence an attempt has to be made to enroll all patients for these upgraded treatments.


  Conclusion Top


This audit was a first of its kind in our institution and was conducted in 2016, which evaluated the standard of patient care for the carcinoma of the cervix in 2010. It identifies avenues for improvement and provides a baseline for further audits.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Nandakumar A, Ramnath, Chaturvedi M. The magnitude of cancer cervix in India. Indian J Med Res 2000;130:219-21.  Back to cited text no. 1
    
2.
Höckel M, Kahn T, Einenkel J, Manthey N, Braumann UD, Hildebrandt G, et al. Local spread of cervical cancer revisited: A clinical and pathological pattern analysis. Gynecol Oncol 2010;117:401-8.  Back to cited text no. 2
    
3.
Hospital Based Cancer Registry. Kidwai Cancer Institute; 2009.  Back to cited text no. 3
    
4.
Shah B, Nandakumar A, Shukla DK. National Centre for Disease Informatics Research, National Cancer Registry Programme, ICMR Three Year Report of Population Based Registries, 2009-2011 Bangalore, India: NCDIR-NCRP (ICMR) 2014. Available from: https://ncdirindia.org/NCRP/ALL_NCRP_REPORTS/PBCR_REPORT_2012_2014/ALL_CONTENT/PDF_Printed_Version/Preliminary_Pages_Printed.pdf. [Last accessed on 2022 Jun 24].  Back to cited text no. 4
    
5.
Chopra S, Gupta M, Matthew A, Mahantshetty U, Engineer R, Lavanya G, et al. Locally advanced cervical cancer: A study of 5-year outcomes. Indian J Cancer 2018;55:45-9.  Back to cited text no. 5
[PUBMED]  [Full text]  
6.
Gupta T, Epari S, Moiyadi A, Shetty P, Goda JS, Krishnatry R, et al. Demographic profile, clinicopathological spectrum, and treatment outcomes of primary central nervous system tumors: Retrospective audit from an academic neuro-oncology unit. Indian J Cancer 2017;54:594-600.  Back to cited text no. 6
[PUBMED]  [Full text]  
7.
Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A III. AJCC Manual of Staging. 7th ed. New York: Springer; 2010.  Back to cited text no. 7
    
8.
Cervical cancer. NCCN clinical practice guidelines in oncology 2009. (Accessible with permission from NCCN).  Back to cited text no. 8
    
9.
Green JA, Kirwan J, Tierney J, Vale C, Symonds P, Fresco L, et al. Concomitant chemotherapy and radiation therapy for cancer of the uterine cervix. Cochrane Database Syst Rev 2005;CD002225.   Back to cited text no. 9
    
10.
Vale C, Tierney JF, Stewart LA, Brady M, Dinshaw K, Jakobsen A, et al. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: A systematic review and metaanalysis of individual patient data from 18 randomized trials. J Clin Oncol 2008;26:5802-12.  Back to cited text no. 10
    
11.
Halperin EC, Wazer DE, Perez CA, Brady LW. Perez and Brady's Principles and Practice of Radiation Oncology. 6th ed. Philadelphia: Lippincott William & Wilkins; 2013. p. 1484.  Back to cited text no. 11
    
12.
Landberg T, Chavaudra J, Dobbs J, Gerard JP, Hanks G, Horiot JC, et al. ICRU Reports. Reports of the International Commission on Radiation Units and Measurements. 1999;os-32(1):48-51. Available from: https://doi.org/10.1093/jicru_os32.1.48. [Last accessed on 2020 Jun 24].  Back to cited text no. 12
    
13.
Small W, Mell LK, Anderson P, Creutzberg C, De Los Santos J, Gaffney D, et al. Consensus guidelines for the delineation of the clinical target volume for intensity modulated pelvic radiotherapy in the postoperative treatment of endometrial and cervical cancer. Int J Radiat Oncol Biol Phys 2009;71:428-34.  Back to cited text no. 13
    
14.
Bagshaw HP, Pappas LM, Kepka DL, Tward JD, Gaffney DK. Patterns of care with brachytherapy for cervical cancer. Int J Gynecol Cancer 2014;24:1659-64.  Back to cited text no. 14
    
15.
Pötter R, Georg P, Dimopoulos JC, Grimm M, Berger D, Nesvacil N, et al. Clinical outcome of protocol based image (MRI) guided adaptive brachytherapy combined with 3D conformal radiotherapy with or without chemotherapy in patients with locally advanced cervical cancer. Radiother Oncol 2011;100:116-23.  Back to cited text no. 15
    
16.
Girinsky T, Rey A, Roche B, Haie C, Gerbaulet A, Randrianarivello H, et al. Overall treatment time in advanced cervical carcinomas: A critical parameter in treatment outcome. Int J Radiat Oncol Biol Phys 1993;27:1051-6.  Back to cited text no. 16
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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