Longitudinal Changes in Active Bone Marrow for Cervical Cancer Patients Treated With Concurrent Chemoradiation Therapy

Abstract

SummaryHematologic toxicity (HT) is a common adverse effect in patients with cervical cancer treated with concurrent chemoradiation therapy. In this study, we used 18 F-fluorodeoxyglucose positron emission tomography to quantify changes in functional bone marrow (BM) in unirradiated (extrapelvic) and irradiated (pelvic) BM in cervical cancer patients treated with concurrent chemotherapy of varying intensities. We found that patients have varying Purpose: To quantify longitudinal changes in active bone marrow (ABM) distributions within unirradiated (extrapelvic) and irradiated (pelvic) bone marrow (BM) in cervical cancer patients treated with concurrent chemoradiation therapy (CRT). Methods and Materials: We sampled 39 cervical cancer patients treated with CRT, of whom 25 were treated with concurrent cisplatin (40 mg/m 2 ) and 14 were treated with cisplatin (40 mg/m 2 ) plus gemcitabine (50-125 mg/m 2 ) (C/G). Patients underwent 18 F-fluorodeoxyglucose positron emission tomographic/computed tomographic imaging at baseline and 1.5 to 6.0 months after treatment. ABM was defined as the subvolume of bone with standardized uptake value (SUV) above the mean SUV of the total bone. The primary aim was to measure the compensatory response, defined as the change in the log of the ratio of extrapelvic versus pelvic ABM percentage from baseline to after treatment. We also quantified the change in the proportion of ABM and mean SUV in pelvic and extrapelvic BM using a 2-sided paired t test. Results: We observed a significant increase in the overall extrapelvic compensatory response after CRT (0.381; 95% confidence interval [CI]: 0.312, 0.449) and separately in patients treated with cisplatin (0.429; 95% CI: 0.340, 0.517) and C/G (0.294; 95% CI: 0.186, 0.402). We observed a trend toward higher compensatory response in patients treated with cisplatin compared with C/G (PZ.057). Pelvic ABM percentage

Potential of Proton Therapy to Reduce Acute Hematologic Toxicity in Concurrent Chemoradiation Therapy for Esophageal Cancer

“…One limitation of our study was that we used the external bone contour as a surrogate for active bone marrow, although the distribution of the active marrow might be very different for each patient and would influence the active bone marrow-sparing possibilities for each individual patient. The idea of a compensatory response in nonirradiated bone has also been proposed (11) , and sparing a sufficient bone marrow reserve from even low doses in the thoracic region would suggest that protons should be used, especially for patients with a small absolute bone volume or receiving intense concurrent chemotherapy regimens. Future work would ideally require imaging of active bone marrow for each patient, to identify the region of active bone marrow to be spared and to select those patients who would benefit sufficiently from reoptimized photon plans or those requiring proton planning to reduce their risk of acute HT.…”

“…Most of the data concerning the risk of HT and bone marrow irradiation have been collected from studies of anal cancer (9) or cervical cancer 10 , 11 , in which the large planning treatment volumes (PTVs) often abut or overlap the pelvic bones (pelvis, sacrum, lumbar spine). The pelvic bones, combined, contain ∼50% of the body's active bone marrow.…”

“…Reduced HT in cervical cancer (12) and reductions in HT for anal cancer (13) treated with IMRT and scanned proton therapy (14) have been reported. These delivery techniques can also be combined with functional imaging to identify active bone marrow regions within the pelvis to guide dose optimization 11 , 15 , 16 . The dose to subsites of the pelvic bone (eg, lumbosacral spine, which contains 25% of the bone marrow) has also been identified as an important predictor of HT (17) , and preferential dose sparing to a subregion of pelvic bone might be more easily achieved.…”

Bone marrow sparing RT in era of immunotherapy

“…The indirect proof of relevance of PET based delineation of BM may be a decreased SUV in BM regions after irradiation in FDG-PET imaging [79,89,90]. BM suppression (measured as reduction of SUV) correlated with different CBC values [79,89].…”

Pelvic bone marrow sparing intensity modulated radiotherapy reduces the incidence of the hematologic toxicity of patients with cervical cancer receiving concurrent chemoradiotherapy: a single-center prospective randomized controlled trial

“…Various retrospective studies have demonstrated a correlation between RT dosimetric parameters and the incidence of acute HT [ 14 – 22 ]. Intensity modulated radiation therapy (IMRT) has a unique advantage in pelvic bone marrow sparing (PBMS) [ 23 – 25 ].…”