Prevalence of Cervical cancer is high in developing nations and it is estimated that close to 569,847 new cases and 311.356 deaths, related to carcinoma cervix were noted in 20181. Concurrent chemo-radiotherapy is used as a standard treatment protocol. Concurrent chemo-radiotherapy has significantly improved tumor control, overall survival and progression free survival2. Many studies have reported that when the planned dose is delivered to the tumor using conventional techniques such as, 2D and 3DCRT, a larger volume of bone marrow is irradiated and higher dose is delivered to the exposed bone marrow[3,4. More than 50% of active bone marrow in adults is located in the pelvic and neighboring bones , which, when irradiated during the pelvic radiotherapy leads to decrease in the level of blood counts3 . Concurrent chemo-radiotherapy to pelvis increases the hematological toxicity (HT) particularly leucopenia, neutropenia and thrombocytopenia. This Hematological Toxicity can cause uncalled interruption in the radiotherapy schedule or reduction in the no. of chemotherapy cycles scheduled. The fore mentioned problems results in reduced tumor control and accelerated tumor progression5. As a result, sparing bone marrow as much as possible has become a priority in delivering precision RT6. Using IMRT/VMAT radiation doses can be delivered with high conformality, while avoiding nearby critical structures. The benefits of IMRT/VMAT were documented in head and neck cancer7,8, prostate cancer3,9. The results of RTOG 0418 phase II trial shown hematological toxicities can be associated with mean dose and higher dose irradiation volume of BM10 [10].Few studies associated hematological toxicity with V_10Gy% and V_20Gy%11,12. The usage of image guided volumetric modulated arc therapy technique (IG/VMAT) is on raise in recent times and its role is well established13.Aim of the present study is to investigate Dose Volume Histogram parameters between state of the art technique IGRT/VMAT plan with and without bone marrow sparing and compare the results.

The present study is a retrospective Dosimetric study conducted on 10 consecutive patients of biopsy-proven invasive cervical cancer attending the outpatient department of Geetanjali cancer centre, Udaipur, Rajasthan, India between January 2019 and April 2019. As per FIGO14 two patients were IIB, two patients were IIIA, six patients were IIIB. For treatment planning, patients were scanned on a GE Optima-520, 16 slice fan-beam CT (FBCT) scanner with 2.5 mm slice thickness in the supine position on a customized vacuum cushion with simulation tattoos and alignment lasers. All the simulation scans were taken after following a bladder and bowel preparation protocol, aimed at an empty rectum and full bladder, starting prior to the initial planning scan and continuing throughout the treatment. The bowel preparation consists of a low bulk diet, and rectum voiding before treatment. The bladder preparation requires 1 litre of water to be consumed 30 min before planning scan and every treatment time. Fludicial markers were inserted into the vaginal cuff to visualize it on CT images. CT images were obtained from T12 to middle third of femur. Oral and intravenous contrast were administered to all the patients before acquiring CT images.

Gross Tumor volume (GTV) defined as gross tumor, its extent and positive lymph nodes as seen on the image. CTV was defined, based on the primary tumor extent and positive node involved with an additional margin for including microscopic spread. PTV was created from the CTV with an additional margin of 5-7 mm in all direction. Based on standard Radiation Therapy Oncology Group guidelines (RTOG)15,16,17. Organ at Risk included bladder, rectum, both femoral head, small bowel and the bone marrow . The low-density regions inside the bone were contoured by free hand as the surrogate for BM as demonstrated by Mahanshetty et al18. To bring uniformity the widow was adjusted to bone range while contouring the surrogate for bone marrow. All contouring was done by a single physician and verified by another physician for all plans, so that inter-observer variations could be eliminated. The cranial border of bone marrow contour began at 1 cm above the uppermost border of planning target volume (PTV) and ended at 1 cm below the lower border of the PTV. The rectum was outlined up to sigmoid flexure. The small bowel included the entire peritoneal cavity (not individual loops of bowel) up to L3. The prescribed dose to PTV was 50Gy in 25 fractions (2Gy/fraction) and from second week of radiotherapy 50mg/m²/week cisplatin chemotherapy was administered for five weeks.

Two sets of plans were generated for all the 10 patients using Volumetric Arc Radiotherapy (VMAT) in Monaco v 5.11.02(Elekta, Crawley, UK) treatment planning system , using Monte Carlo Algorithm using two full arcs.3mm grid space along with 5mm minimum segment width was used for all the plans. Keeping all constraints in mind planning optimization was performed with no compromise in coverage of PTV.

V95 of PTV received ≥ 95% of the prescribed dose in both Bone Marrow Sparing and Normal VMAT plan. Constraints for bowel bag V40 < 30%, for rectum and bladder V40 < 50-60% and for both femoral head V30 < 20%. Constraints to bone marrow were V10 < 90% and V 20 < 75% of prescribed dose.

Before treatment delivery CBCT scans were acquired in Elekta XVI with software version 5.0.2, using large volume scan protocol mode settings 120 kV, 80 mA, 28 mAs and acquisition angle range 360, maximum reconstruction diameter 40 cm, using the half-fan bowtie filter for Image Guided Radiotherapy during 25 fraction treatment course. Positional error, if any, were corrected and the prescribed dose was delivered.

Dosimetric comparisons of plans were done based on the following parameters extracted from dose volume histogram (DVH): homogeneity index (HI), conformity index (CI), V5, V10, V20, V30, V40 of pelvic bone marrow,V10, V20, V30, V40 of small bowel, V20, V30,V40 of bladder and V10, V20, V30, V40 of rectum. The HI was used to analyze the dose uniformity and defined as D5/D95. The lower the HI, the better the dose homogeneity. CI = the percentage of the PTV volume receiving at least 50 Gy × the ratio of the volume of the PTV receiving at least 50 Gy to the total 50 Gy volume. The closer the CI value was to 1, the better the dose conformity19.

SPSS software was used in analyzing the data (version 20.0,SPSS Inc, USA). Data was expressed in the form of mean ± standard deviation (χ ± s). Paired two-tailed students t test was used to evaluate the significance of differences.

Homogenisity index and conformity index of the PTV coverage

Treatment of carcinoma cervix is restricted as a result of toxicity of the surrounding normal structures and HT. HT could be significantly reduced by bone marrow sparing, which could be aided by IGRT/VMAT. This modality could allow completion of treatment with prescribed dose and concurrent chemotherapy in allotted stipulated time. More prospective randomized control trials are needed, to prove its efficacy.