Correlation of Dose to Bone Marrow With Hematological Toxicity and MRI Based Estimation of Conversion of Active to Inactive Bone Marrow in Long Course Neo adjuvant Chemoradiation for Locally Advanced Rectal Cancer

Aims : To correlate the dose to bone marrow with the incidence and grade of hematological toxicity and to estimate the extent of inactivation of bone marrow in patients with locally advanced rectal cancer undergoing neo adjuvant long course chemoradiation. Methods and materials: 20 patients with locally advanced rectal cancer were enrolled for the study after clearance from the institution review board. All the patients received preoperative long course radiotherapy using 3D conformal modality to a dose of 50.4Gy.They received concurrent chemotherapy with daily Capecitabine (825mg/m2). The entire pelvis was contoured on the simulation CT, the active marrow (red) bone marrow was delineated on both the pre radiotherapy as well as the post radiotherapy MRI of the pelvis on the T1 weighted images. Baseline and weekly blood investigations were recorded during the course of therapy. The dosimetric parameters such as V5, V10, V20, V30 and V40 were correlated with the incidence of Grade 3 or more hematological toxicity. The pre and post radiotherapy volumes of the active marrow and the extent (in percentage volume) of inactivation of bone marrow (red to yellow marrow conversion) due to LCCRT was also documented. The Shapiro Wilk/Mann Whitney test was used to correlate the bone marrow dose with toxicities and the paired T test was used to test the significance of conversion of active to inactive marrow. Results: The incidence of grade 3 or more toxicity of hemoglobin correlated with V30 and V40 values(p value 0.02 and 0.0095 respectively). The toxicity grades of the other blood elements however did not show any correlation with any of the dosimetric variables. The median value of the pre radiotherapy active marrow was 346.21cc and the median of the post radiotherapy active marrow was 116.44cc.The percentage inactivation after therapy had a median value of 57.64% (range 38.98% - 83.39%)There was also a significant conversion of active to inactive bone marrow as detected on the MRI, the correlation of the pre and post neoadjuvant chemoradiotherapy marrow volumes was highly significant (p value <0.0001) Conclusion: The volume of pelvic bone marrow receiving at least 30Gy or more in patients undergoing long course chemoradiotherapy for locally advanced rectal cancer has a significant impact on anemia. There was also a significant conversion of active to inactive bone marrow as detected on the MRI. The significant myelosuppression associated with the use of both chemotherapy and radiotherapy in the management of rectal cancer warrants efforts to limit the toxicity to the bone marrow. The use of MRI and other functional imaging for visualization and delineation of the bone marrow and its use in radiotherapy planning is now providing possibilities to further limit normal tissue toxicity