Session Item

Cervical cancer is the 2nd most common women’s cancer in India, the majority present in locally advanced stages (LACC) where the standard treatment is chemo-radiation (CT-RT). Definitive IMRT for LACC is prone to geographic miss due to daily positional and volumetric variations in pelvic organs. Hence, despite evidence of reduced treatment-related toxicities, implementation of IG-IMRT with a reasonable safety margin is complex & challenging.

In this prospective, interventional, non-randomized phase II study, patients diagnosed with carcinoma cervix FIGO (2009) stage IB2-IIIB (age 18 to 65 years) were treated with definitive pelvic CT-RT with pre-specified organ (bladder and rectum) filling protocol. Reproducibility of organ filling was assessed along with the implementation of daily adaptive IG-IMRT, with a library of 3 IMRT plans with incremental expansions of CTV to PTV (primary) margins (small 0.7 cm, adequate 1 cm & large 1.5 cm) and a backup motion robust 3DCRT plan; the appropriate plan is chosen based on pre-treatment CBCT (‘Plan of the Day’ approach).

47 patients (median age 49 years; IQR 45-56), received definitive pelvic RT (45-46 Gy in 23-25# with SIB to gross nodes in 15 patients) with the said IGRT protocol.  In the analysis of 1099 CBCT images (in 1111 RT sessions), mean planning CT and CBCT bladder volumes were 414.5 ccs and 374.5 ccs respectively with large inter-fractional variation; mean absolute dispersion being 29.6% with respect to planning CT. Significant influential random factors were post-chemotherapy sessions (p=0.000), pre-RT protocol duration (p=0.001), grades of CINV & cystitis (p=0.002) and any presence of comorbidity (Spearman’s R=0.328; p=0.024). Time-trend analysis revealed an absolute systemic reduction of 20% in bladder volume means from 1st to 5th week. Rectal volume variation was much less pronounced with 19.6% mean dispersion, with no significant factors affecting it.

While in 19.4% and 2.1% of sessions ‘Large’ PTV and ‘3DCRT’ was necessary to cover the CTV respectively, reduction in treated volume was possible in 42.1% of sessions choosing ‘Small’ PTV instead of standard ‘Adequate’ PTV (out of 78.5%, ‘Adequate’ was used in 36.4% sessions). ‘Plan of the day’ selection had a moderate-strong correlation with non-absolute dispersion of bladder filling (Spearman’s R=0.41; p=0.001) and a weak (but significant) correlation with grades of acute toxicities. The planned protocol was well tolerated with no RT-induced local grade III toxicity.

Inter-fractional variation in organ filling (esp. bladder) is inevitable despite fixed pre-treatment protocol in definitive LACC. Variation in bladder filling is patient-specific, multi-factorial and has a systemic component. Despite the logistical challenges and inherent heterogeneity in the selection of ‘plan of the day’; adaptive IG-IMRT based on incremental CTV-to-PTV margins is a feasible and promising strategy to minimize geometric uncertainties in radical RT of cervical cancer.