Conventional radiotherapy or 2-dimensional radiotherapy uses bony landmarks to define the target volume for pelvic radiotherapy. Treatment is delivered either with anterior and posterior opposed fields or with a four-field box technique, which reduces the volume of small bowel in the treated volume [1,2].

However, these techniques, based on generic bony landmarks as surrogates for the clinical target volume (CTV), do not lend themselves to customized treatment planning using an individual patient’s CTV and results in inadequate coverage of lymph nodes and substantial irradiation of normal organs such as the small bowel, rectum and bone marrow [3,4,5].

Similarly, with MR imaging, the gross tumor definitions and positions during fractionated course of external radiation have questioned the conventional borders and margins, especially the antero‑posterior borders due to variable ante‑versions and ante‑flexions at uterus and bladder-rectum movements.

Three-dimensional conformal radiotherapy combines multiple radiation fields to deliver precise dose of radiation to the affected area. Tailoring each of the radiation fields to focus on the tumor delivers a high dose of radiation to the tumor and avoids nearby healthy tissue.

3DCRT has been shown to give better and more precise target coverage (20% reduction in the risk of a geographical miss) and has significantly reduced the volume of radiation-exposed bladder and bowel [3,4,5,6].

The aim of the present study was to evaluate dosimetric comparison and clinical correlation between Conventional Four Field Radiotherapy 1versus Three Dimensional Conformal Radiotherapy in cancer cervix; in terms of the doses received by the planning target volume and organs at risk (rectum, bladder, small intestine and femoral heads) in both groups, dosimetric comparison of Planning Target Volume (PTV) & Organs at risk (OARs) and Clinical correlation of dosimetry with tumour control and side effects.

Study setting: Department of Radiation Oncology, Shri Ram Murti Smarak Institute of Medical

Fig-1: Antero posterior and lateral fields based on bony landmarks for conventional four field box technique.

Three Dimensional Conformal Radiotherapy (Fig-2): Delineation of Gross Tumor Volume (GTV), Clinical target Volume₁ (CTV₁) (including GTV, uterus, vagina, bilateral parametrium), and CTV₂ (Nodal CTV) (including pelvic lymph nodes-common iliac, external iliac, internal iliac, obturator and presacral) was done.

Planning Target Volume (PTV) was taken 1 cm beyond CTV (CTV₁ + CTV₂).

Radiotherapy dose delivered by Linear Accelerator was 50 Gy in 25 fractions at 200 cGy/day in 5 weeks. This was followed by 3 applications of intracavitary brachytherapy of 7 Gy/ fraction each to point A.

Fig-2: Conformal RT volumes in cervical cancer.

Chemotherapy administration:Patients were administered Cisplatin (35mg/m²) on weekly basis during Radiotherapy. The patients were adequately hydrated with 2-2.5 liters of I.V. fluids and supplemented with KCL and MgSO₄.Radiotherapy was delivered within 30 minutes of administration of Cisplatin.

• Small Bowel Dmean (Gy): Mean dose received by the small bowel.
• Femoral heads Dmax (Gy): Maximun dose received by the femoral heads.

1. Clinical response assessment- Clinical response was assessed during radiotherapy and every month after radiotherapy for up to 6 months. The patients were assessed for objective tumor response according to WHO criterion.

Complete response (CR)- Total tumor regression for at least 4 weeks; Partial response (PR)- 50% or more reduction in product of two major perpendiculars of the measurable tumor for at least 4 weeks; Stable disease (SD)- Less than 50% or more reduction to less than 25% increase in cross product; Progressive disease (PD)- Growth of measurable tumor by 25% or more or appearance of new lesion.

1. Complication assessment- Treatment assessment was done on weekly basis during treatment and thereafter monthly basis on follow up. Complete blood counts and kidney function tests and liver function tests were repeated in all patients every week before each chemotherapy cycle.

Hematological toxicities were graded according to common toxicity criteria v4.03. Patients were assessed weekly during chemo radiation for acute radiation reactions. Radiation toxicity was assessed by RTOG acute and late morbidity scoring criteria. Follow up of all patients was done for atleast18 months, from the day of completion of treatment.

Data analysis- Collected data was analyzed using standard statistical methods and SPSS software version 20 to calculate level of significance using “p” value.

Descriptive statistical analysis has been carried out in the present study. Significance is assessed at 5% level of significance and statistical significance considered with p-value of <0.05. Chi-square test has been used to find the significance of haematological and radiation toxicities and clinical response on categorical scale between two groups. 95% Confidence Interval has been computed to find the significant features. Confidence Interval with lower limit more than 50% is associated with statistical significance. Student t test (two tailed, dependent) has been used to find the significance of dosimetric parameters on continuous scale between two groups.

All patients underwent weekly assessment of radiation toxicities during treatment. No significant Grade III/IV haematological toxicity was seen in either group. Haemoglobin was maintained throughout the treatment by blood transfusion, oral hematinics and dietary advice. There were no significant acute and late reactions related to skin, vaginal mucosa, bladder, rectum and small intestine.

Field sizes used for the 3DCRT plans were significantly larger than those used for the conventional plans (p = 0.000) (Table 2). Optimal PTV coverage (95% of the PTV receiving 95% of the prescribed dose) was significantly improved using 3DCRT as compared to conventional radiotherapy (p value = 0.0001).

Table 2: Comparison of field sizes in both groups

Dose homogeneity as assessed by average dose to PTV was not significantly better with 3DCRT (p = 0.292 for average dose to the PTV), while conformity index as assessed by volume receiving 95% of the prescribed dose, the difference was statistically significant between the two groups (p= 0.000). in addition, the mean dose to the planning target volume was increased significantly in the CT based plan when compared with the standard four field plan (p = 0.0001) (Table 3).

Table-3: Comparison of Dosimetric parameters of both groups

Thus, before integrating volumetric planning in our routine practice, the present study was designed to compare conventional four field planning based on standard bony landmarks versus volumetric planning in patients of carcinoma cervix undergoing radiotherapy.

Field Sizes in conventional and 3D conformal planning

Greer et al [8] in their lymphangiographic study found that in 87% of the patients, the common iliac nodes were located proximal to the L5-S1 bifurcation, the conventional upper border of the pelvic portals and recommended that if coverage of the common iliac nodes is desired, the upper border should be moved to the L4- L5 junction. Pendlebury et al [9] also found that 62% of patients required alteration of the conventional pelvic portals based on lymphangiographic findings, with most requiring enlargement of one/more portals while in 20% patients, portals could actually be reduced.

They found that the lateral border of the AP/PA portals and the anterior border of the lateral portals were most often inadequate and recommended 2.5 cm margin from the pelvic brim for the former and 0.5 cm margin anterior to the symphysis pubis for the latter so as to cover 90% of the pelvic nodes. With the advent of CT simulation, it is possible to identify and contour the pelvic blood vessels, and these can then be used as surrogates for localizing the adjacent lymphatics and lymph nodes.

Other lymphangiographic studies by Zunino et al [1] and Bonin et al [10] on the other hand, found that lateral coverage of the external iliac nodes was insufficient on the AP/PA portals and recommended going 2.5 cm and 2.6 cm, respectively, beyond the pelvic brim. In an intra operative study using surgical clips, McAlpine et al [11] recommended that the superior border would need to be even higher at the L3- L4 junction to properly cover the common iliac nodes and also discovered that 26% of patients would have inadequate lateral coverage on the AP/PA portals.

Using noncontract CT images, a study by Finlay et al [6] found that had conventional portals alone been used for radiotherapy planning, the majority (95.4%) of subjects would have had at least one inadequate margin, the majority located superiorly though in around half the subjects, at least one margin would have been generous (>2 cm beyond the blood vessel), usually the lateral borders of the AP/PA portal.

Another study by Gulia A et al [7], observed that in 82% of patients, the standard four field based on bony landmarks failed to encompass the target volume defined by CT as compared with previous studies discussed earlier.

In conjunction with these studies, in the present study it was observed that in only three patients (12%) out of 25 patients, the whole of the planning target volume was encompassed by the standard four field box marked on bony landmarks. Target coverage was significantly improved using 3DCRT as compared to conventional RT (p = 0.0001 for dose to 95% of PTV). On the other hand, dose homogeneity within the PTV was better with 3DCRT as compared to conventional technique but it was not statistically significant (p = 0.292 for average dose to the PTV).

Also, conformity index as evaluated by V95 was also significantly better in 3DCRT group (p = 0.000). In addition, the mean dose to PTV was significantly higher in the CT‑based plan when compared with the standard four field plan. (p = 0.0001 for mean dose to PTV).

OAR Sparing- Silva et al reported that there was a significant increase in the maximum dose received by the OAR, the volume of bowel receiving 30 Gy, and a decrease in the bladder volume receiving 95% of the prescribed dose in the 3D plans as compared to conventional pelvic fields based on bony landmarks [13].

Włodarczyk H et al [14], also concluded that there were significant differences (p<0.05) in dose distributions in critical organs between the 3DCRT and 4 field conventional box techniques. The smallest volumes of critical organs were irradiated using the 4-portal conformal technique. The greatest volume of rectum and bladder was irradiated using the AP-PA conventional technique.

In conjunction to these findings, in the present study also doses to the organs at risk (rectum, urinary bladder, and small bowel) were significantly different across the 2 arms. Doses to the rectum were higher for the 3DCRT arm as compared to the conventional arm but it was statistically insignificant (p = 0.820 for maximum dose to rectum and p = 0.082 for mean rectal dose). But, doses to the urinary bladder were significantly higher for the conventional arm as compared to the 3DCRT arm (p=0.013 for maximum dose tourinary bladder and p=0.024 for mean dose received by urinary bladder, significant).

In the present study, use of CT simulation allowed superior visualization of the pelvic lymph nodes and improved the PTV coverage, mainly by reducing the chances of geographical miss to a minimum. This may translate into superior loco-regional control and even superior survival but longer follow up is needed for such results.

Limitations of present study: Small sample size and short follow up duration.

On dosimetric analysis, three- dimensional conformal radiotherapy gives significantly better PTV coverage when compared to conventional four field box technique. 3DCRT also requires significantly larger field sizes though doses to the OARs are not significantly higher compared to the conventional plans except for small bowel.

Thus, the improved delineation of the target, especially pelvic nodes, and the improved target coverage make 3DCRT a better technique as compared to four field box technique in cases of carcinoma cervix.

However, it remains to be seen whether 3DCRT will have a clinical benefit over conventional four field radiotherapy in terms of loco regional control and overall survival but the answer to the question requires longer follow-up and a larger group ofpatients.

Out of various definitive external beam radiotherapy techniques available for treatment carcinoma cervix like- 2D-CRT, 3D-CRT and IMRT; 2D and 3D-CRT are financially feasible for LMIC (Lower Middle-Income Countries) like India. 3DCRT not only reduces the chances of PTV miss as it is based on cross sectional imaging unlike 2DCRT which is based on bony landmarks but also it provides optimal PTV coverage which is comparable to advanced treatment planning techniques like IMRT at much lower financial expenses.

Dr. Shubhi Agarwal: Data collection and assessment, drafting of manuscript

Dr. Arvind Kumar Chauhan: Verification of data, Manuscript correction and verification