Dosimetric predictors of acute haematological toxicity in oesophageal cancer patients treated with neoadjuvant chemoradiotherapy

Abstract

Objective: Haematological toxicity (HT) is common in patients with oesophageal cancer (EC) treated with chemoradiotherapy (CRT). The Quantitative Analysis of Normal Tissue Effects in the Clinic guidelines provide no dose constraints for the bone marrow (BM) to avoid HT. We aimed to determine dosimetric factors associated with HT during CRT for EC. Methods: 41 patients with EC treated with neoadjuvant cisplatin and 5-fluorouracil-based CRT were retrospectively reviewed. Associations between the dose-volume histogram parameters of thoracic bones and blood cell count changes during CRT were assessed using logistic regression analyses. Receiver-operating characteristic curves were used to derive optimal dosimetric planning constraints. V x indicates the total organ volume percentage exceeding a radiation dose of x (Gy). Results: Greater thoracic vertebrae and rib irradiation doses, including mean vertebral dose (MVD), thoracic vertebrae V 5-30 (TVV 5-30 ), mean rib dose and rib V 5-20 , were associated with increased leukopenia (grade $ 3) risk. Additional BM sites (sternum, scapulae and clavicles) did not influence HT. White blood cell and absolute neutrophil count nadirs were associated with increased irradiation doses to the thoracic vertebrae, ribs and sternum. Chemotherapy cycle number was not significantly associated with severe neutropenia or leukopenia. Cut-off values with the highest likelihood of avoiding leukopenia were MVD , 25.9 Gy, TVV 20 , 70% and TVV 10 , 77%. Conclusion: Thoracic bone irradiation dose was significantly associated with HT after adjusting for chemotherapy effects. Efforts to maintain MVD , 25.9 Gy, TVV 10 , 77% and TVV 20 , 70% could reduce HT. Advances in knowledge: This is the first study addressing issues concerning HT in patients with neoadjuvant CRTtreated EC.

Skeletal Muscle Loss Is an Imaging Biomarker of Outcome after Definitive Chemoradiotherapy for Locally Advanced Cervical Cancer

“…This finding was consistent with previous studies, although the types of diseases and treatments differed (9,41,42). Chemotherapy and radiotherapy are both known to be myelosuppressive and could contribute to hematologic toxicity (43)(44)(45). Bone marrow-sparing radiotherapy could potentially reduce the incidence and severity of hematologic toxicities in patients with LACC (46).…”

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

“…The results when applying the TV dose–volume cutoff values to predict the risk of grade ≥3 leukopenia proposed by Lee et al (23) and Deek et al (22) are listed in Table 1 , including the number of patients (absolute and percentage of group) exceeding the threshold values for each treatment technique. The cutoff values proposed by Lee et al (23) and Deek et al (22) are different, but the trends observed were the same. The SFO62.5 and VMAT62.5bm plans showed the lowest risk of HT, which was greatly reduced compared with the 3D50, VMAT50, and standard VMAT62.5 plans.…”

“…The predicted toxicity rates for the VMAT (10%-29%) and SFO62.5 (0%-10%) plans were much lower. However, the cutoff values from Lee et al (23) predicted a much lower incidence of grade >3 leukopenia for all treatment techniques, with a maximum of 14% of 3D50 patients predicted to experience HT.…”

“…A recent study of 52 lung cancer patients treated with 3-dimensional (3D) conformal radiation therapy and IMRT found the TV dose parameters (mean dose, V 20Gy , and V 30Gy ) were associated with the risk of grade ≥3 leukopenia (22) . A study of 41 esophageal cancer patients investigated similar dose–volume parameters (TV mean dose, V 20Gy , and V 10Gy ) to propose cutoff values to avoid the development of grade ≥3 leukopenia (23) . The size and position of the target volumes also means that the potential for dose sparing of the bone marrow in the thorax might be greater than that for the pelvis, especially if IMRT, VMAT, or proton therapy is used.…”

Bone marrow sparing RT in era of immunotherapy

“…National Comprehensive Cancer Network (NCCN) guidelines indicate that IMRT should only be administrated for unique clinical situation like reirradiation or inside clinical trials [9]. Limited data regarding BMS-RT are available for esophageal and gastric cancer [60,61]. Two main approaches for BMS-RT are: 1) dose reduction in total bone marrow (BMtot)-delineated as entire bone volume near planning target volume and 2) division of bone marrow on basis of functional imaging to red (active) bone marrow (BMact) and yellow (inactive) bone marrow (BMinact).…”