Dose-Volume Parameters of Spared Magnetic Resonance Imaging-Defined Active Bone Marrow Predict Hematologic Toxicity in Pelvic Malignancies Patients Undergoing Radiotherapy: A Cohort Study.

Background: The objective of this investigation is to evaluate the superiority of dose-volume parameters relying on magnetic resonance imaging (MRI)-defined active bone marrow (ABM) over those based on total bone marrow (TBM) contoured via CT in the prediction of hematologic toxicity (HT) occurrence among patients with pelvic malignancies undergoing radiotherapy. Methods: The clinical data of 116 patients with pelvic malignancies treated with pelvic radiotherapy were analyzed retrospectively. The ABM areas on T1-weighted MRI were contoured. The statistical significance between TBM and ABM dose-volume measures was assessed through the utilization of either Student's t-test or Wilcoxon signed rank test. Logistic and linear regression models were employed to analyze the correlation between dose-volume parameters (V5-V50) and HT occurrence in pelvic ABM and TBM. Receiver operating characteristic (ROC) curves were used to compare predictors of HT2+. Results: There were significant differences in dosimetric parameters between ABM and TBM. Logistic regression analysis showed that ABM V5, ABM V10, ABM V15, ABM V20, and TBM V5 were significantly associated with the occurrence of HT2+ in pelvic malignancies. Linear regression analysis showed that ABM V5, ABM V10, and ABM V15 were significantly associated with white blood cell (WBC), absolute neutrophil count (ANC), hemoglobin (Hb), and lymphocyte (Lym) nadir. ABM V5, ABM V10, ABM V15, and ABM V30 were predictive of HT2+. Conclusions: More accurate prediction of HT in patients receiving pelvic radiotherapy may be achieved by relying on dose-volume parameters of MRI-based ABM. Further prospective studies are needed to confirm this.

The effect of radiotherapy time and dose on acute hematologic toxicity during concurrent postoperative chemoradiotherapy for early high-risk cervical cancer.

Objective: This study aims to analyze the characteristics and factors that influence acute hematological toxicity (HT) during concurrent chemoradiotherapy (CCRT) for cervical cancer, as well as to provide reference data for clinical practice. Methods: Patients with FIGO IB1-IIA2 cervical cancer who underwent CCRT from May 2018 to August 2020 were included in this study retrospectively. All patients had received external beam radiation therapy and platinum-based concurrent chemotherapy. HT was assessed according to CTCAE 5.0. The pelvic bone marrow was redrawn on the original CT images and divided into four parts: the whole pelvic bone marrow (WP-BM), iliac bone marrow (IL-BM), lower pelvic bone marrow (LP-BM), and lumbosacral bone marrow (LS-BM). The radiation dose and volume of each part of the pelvic bone marrow were recalculated in a new plan created using the original planning parameters. The corresponding dose-volume histogram (DVH) was generated to obtain the bone marrow volumes receiving 10Gy, 20Gy, 30Gy, 40Gy, 45Gy, and 50Gy. Results: In 112 patients, the incidences of grade 2 or higher leukopenia, anemia, thrombocytopenia, and neutropenia were 49.1%, 2.7%, 1.8%, and 20.5%, respectively. Leukopenia was linked to LS-V20 (r = -0.310; P = 0.006) and radiotherapy treatment lengths (days) (r = -0.416; P = 0.013). Anemia was associated with WP-V30, WP-V40, WP-V45, WP-V50, IL-V20, IL-V40, ILV45, IL-V50, LP-V30, LP-V40, LP-V45, and LP-V50 (P <0.05). Thrombocytopenia (r = -0.304, P = 0.007) and neutropenia (r = -0.368, P = 0.009) was associated only with the length of radiotherapy treatment (day). Multiple regression analysis showed that only anemia was negatively correlated with WP-V30, IL-V40, and LP-V40 (P <0.05). Conclusions: Acute HT during CCRT in early-stage high-risk cervical cancer may be related to the duration of radiotherapy and the volume of different radiotherapy doses received at different parts in the pelvic bone marrow.

A radiomics approach for predicting acute hematologic toxicity in patients with cervical or endometrial cancer undergoing external-beam radiotherapy.

PURPOSE: This study is purposed to establish a predictive model for acute severe hematologic toxicity (HT) during radiotherapy in patients with cervical or endometrial cancer and investigate whether the integration of clinical features and computed tomography (CT) radiomics features of the pelvic bone marrow (BM) could define a more precise model. METHODS: A total of 207 patients with cervical or endometrial cancer from three cohorts were retrospectively included in this study. Forty-one clinical variables and 2226 pelvic BM radiomic features that were extracted from planning CT scans were included in the model construction. Following feature selection, model training was performed on the clinical and radiomics features via machine learning, respectively. The radiomics score, which was the output of the final radiomics model, was integrated with the variables that were selected by the clinical model to construct a combined model. The performance of the models was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: The best-performing prediction model comprised two clinical features (FIGO stage and cycles of postoperative chemotherapy) and radiomics score and achieved an AUC of 0.88 (95% CI, 0.81-0.93) in the training set, 0.80 (95% CI, 0.62-0.92) in the internal-test set and 0.85 (95% CI, 0.71-0.94) in the external-test dataset. CONCLUSION: The proposed model which incorporates radiomics signature and clinical factors outperforms the models based on clinical or radiomics features alone in terms of the AUC. The value of the pelvic BM radiomics in chemoradiotherapy-induced HT is worthy of further investigation.

Clinical study of acute toxicity of pelvic bone marrow-sparing intensity-modulated radiotherapy for cervical cancer.

OBJECTIVES: To compare the dose volume of the target area and the toxicity of pelvic bone marrow-sparing intensity-modulated radiotherapy (PBMS-IMRT) with routine IMRT in patients undergoing radiochemotherapy for cervical cancer. MATERIAL AND METHODS: Forty patients with indications for adjuvant radiochemotherapy after cervical cancer surgery were selected and randomly divided into IMRT (n = 20) and PBMS-IMRT (n = 20) groups to observe and record the toxicity and its severity in the blood, gastrointestinal tract, and genitourinary system. RESULTS: There was no significant difference in the target area conformity index (CI) or homogeneity index (HI) between the two groups (p > 0.05). The pelvic bone V10-V50 in the PBMS-IMRT group were lower than those in the IMRT group (p < 0.05), and there was lower hematological toxicity (p < 0.05) and fewer delays or interruptions in chemotherapy and/or radiotherapy (p < 0.05) in the PBMS-IMRT group. The toxicity to the gastrointestinal and genitourinary systems in the two groups was not significantly different (p > 0.05). CONCLUSIONS: PBMS-IMRT significantly reduced the dose volume of the pelvic bone marrow, thereby reducing the incidence of bone marrow suppression. However, it had no significant impact on the gastrointestinal or genitourinary systems.

Relationship between the pelvic bone marrow dose-volume parameters and acute hematologic toxicity in neoadjuvant pelvic intensity-modulated radiotherapy for local advance rectal cancer / 中华放射医学与防护杂志

Objective:To analyze the correlation between the volume of irradiated pelvic bone marrow and acute hematologic toxicity (HT), in order to provide clinical data to reduce the risk of acute HT and optimize the radiotherapy plan.Methods:From October 2017 to May 2019, 41 LARC patients who received neoadjuvant concurrent chemoradiotherapy (CCRT) were retrospectively reviewed in our center. All patients were treated with 5-field intensity-modulated radiotherapy (IMRT), and the prescription dose delivered to PTV was 45-50.4 Gy in 25-28 fractions. Capecitabine or 5-fluorouracil (5-FU) wasadministered daily 5 days a week during radiotherapy. Different HTswere recorded according to National Cancer Institute Common Toxicity Criteria Version 5.0 (NCI-CTC.V5.0) based on laboratory tests. The volume of PBM or each site (coxal, sacrum, femoral) receiving more than x Gy refers to as TVx, CVx, SVx, and FVx, respectively. Logistic regression was performed to evaluate the association between the volume of irradiated pelvic bone marrow and different HT. Generalized additive model (GAM) and piecewise regression were used to further analyze the possible nonlinear relationship and threshold effect between them. Results:Multivariate logistic regression analysis showed that low-dose of irradiated total pelvic bone marrow volume ( TV5) and coxal bone marrow volume ( CV5, CV10) were significantly correlated with Grade ≥2 leukopenia( P<0.05). There was a significant negative correlation between the sacrum bone marrow volume ( SV5, SV10) and Grade ≥2 leukopenia ( P<0.05). A thresholdeffect has been observed between CV10 and Grade ≥2 leukopenia by Generalized additive model (GAM) and piecewise linear regression. The threshold between CV10 and Grade ≥2 leukopenia was 575 ml, OR (95% CI) was 1.85 (1.08, 3.16). Conclusions:In neoadjuvant IMRT of rectal cancer, CV is a better predictor of acute HT induced by CCRT than TV. The irradiated volume of CV associated with acute HT was mainly low-dose levels ( CV5, CV10). The thresholds of our study ( CV10= 575 ml) could be a good reference for the optimization of the radiotherapy plan.

Effect of Pelvic Bone Marrow Sparing Intensity Modulated Radiation Therapy on Acute Hematologic Toxicity in Rectal Cancer Patients Undergoing Chemo-Radiotherapy.

BACKGROUND: While chemo-radiotherapy improves local control in patients with locally advanced rectal cancer, it can also increase acute hematological toxicity (HT), which leads to poor outcomes. Patients receiving bone marrow radiation have been shown to develop acute HT. However, the safety and efficacy of bone marrow sparing is undetermined. The aim of our study was to explore the feasible dosimetric constraints for pelvic bone marrow (PBM) that can be widely used in rectal cancer patients undergoing chemo-radiotherapy. METHODS: 112 rectal cancer patients were selected and divided into the PBM sparing IMRT group (60 cases) and the non-PBM sparing IMRT group (52 cases). All patients underwent pelvic radiotherapy with concurrent capecitabine-based chemotherapy. The PBM dosimetric constraints in the PBM sparing IMRT group were set to:V10 ≤ 85%, V20 ≤ 65% and V30 ≤ 45%. An independent sample t test was applied for the dose-volume parameters, and Chi-squared analysis was applied for clinical parameters and adverse events. RESULTS: The radiation dose to PBM (V5~V45, Dmean, P<0.05), PBM sub-regions (V10~V35, Dmean, P<0.05) and both femoral heads (V5~V40, Dmean, P<0.05) decreased significantly in the PBM sparing IMRT group compared with that of the non-PBM sparing IMRT group (P<0.05). There was no significant difference in any dose-volume parameters of the bladder and small bowel in either groups, and none in the planning target volume (PTV) dose homogeneity and conformity (P>0.05). For acute HT observation, the incidence of grade 3 acute HT (χ2 = 7.094, P=0.008) was significantly reduced in patients treated with PBM sparing IMRT compared with patients treated with non-PBM sparing IMRT. There was no statistical difference in the incidence of vomiting, diarrhea, fatigue, anorexia, nausea, hand-foot syndrome, cystitis, perianal pain and perianal dermatitis in patients of both groups (P >0.05). CONCLUSIONS: Applying PBM dosimetric constraints (V10 ≤ 85%, V20 ≤ 65% and V30 ≤ 45%) can significantly reduce the radiation dose to PBM. The patients treated with PBM sparing IMRT had a lower incidence of acute HT compared with those treated with non-PBM sparing IMRT. Applying the PBM dosimetric constraints proposed by our study can benefits the patients with rectal cancer undergoing capecitabine-based chemo-radiotherapy.

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.

PURPOSE: To test the efficacy and feasibility of pelvic bone marrow sparing intensity modulated radiotherapy (PBMS-IMRT) in reducing grade 2 or higher hematological toxicity (HT2+) for patients with cervical cancer treated with concurrent chemoradiotherapy. METHODS AND MATERIALS: A total of 164 patients with Stage Ib2-IIIb cervical cancer were prospectively enrolled from March 2018 to March 2019 at a single center and were randomly allocated into the PBMS group or the control group. The control group received weekly cisplatin concurrently with IMRT, followed by intracavitary brachytherapy. The PBMS group additionally received PBM dose constraint. The dosimetric parameters of the pelvic bone (PB) and the subsites including hip bone (HIP) and lumbosacral spine (LSS) and the corresponding bone marrow were recorded. The endpoint of the trial was acute hematologic or gastrointestinal toxicity. Receiver operating characteristic curves were used to derive optimal dosimetric planning constraints. RESULTS: Eighty-two patients in the PBMS group and 82 in the control group were enrolled for statistical analysis. The incidence of HT2+ in the PBMS group was 50.0%, significantly lower than the 69.5% incidence in the control group (P = 0.02). Patients with PB V40 ≥ 28% were more likely to experience HT2+ (OR = 2.85, P = 0.006), while the incidence of grade 2 or higher gastrointestinal toxicity (GT2+) events did not differ significantly between the two groups (P > 0.05). Dosimetric parameters of LSS showed stronger associations with HT2+ than other subsites. The patients with LSS V10 ≥ 87% and LSS mean ≥ 39 Gy were more likely to experience HT2+ (OR = 3.13, P = 0.001;OR = 3.03, P = 0.002, respectively). CONCLUSION: PBMS-IMRT reduced HT compared with IMRT alone. Efforts to maintain LSS V10 < 87%, LSS mean < 39 Gy and PB V40 < 28% simultaneously may reduce the risk of HT2 +. TRIAL REGISTRATION: The trial was registered with Chinese clinical trial registry ( ChiCTR1800015069 ).

Response of FDG avid pelvic bone marrow to concurrent chemoradiation for anal cancer.

BACKGROUND AND PURPOSE: To determine if suppression of active bone marrow, as defined on FDG PETCT, is seen in on-treatment imaging of anal cancer patients receiving concurrent chemoradiation. METHODS AND MATERIALS: Scans from 26 patients participating in the ART trial (full title: Anal squamous cell carcinoma: Investigation of functional imaging during chemoRadioTherapy), a single center observational study with FDG PETCT prior to radiotherapy and at fraction 8-10 of concurrent chemoradiation were analysed. Active bone marrow was contoured in both the pelvis and un-irradiated thoracic spine. SUV and volume of active bone marrow after 8-10 fractions of treatment were compared to baseline. Dose metrics to pelvic active bone marrow were extracted and compared to reduction in SUV/active bone marrow volume and to blood count nadir using linear regression. RESULTS: Suppression of active bone marrow is seen in the pelvis by a reduction in mean SUV and volume of active bone marrow after 8-10 fractions of treatment. Suppression is not seen in un-irradiated thoracic spine. Dose metrics were associated with reduced SUV and reduced volume of active bone marrow. Volume of active bone marrow receiving <20 Gy was associated with WCC/ANC nadir. 20 Gy was identified as the most likely clinically meaningful dose threshold for toxicity. Volume of active bone marrow receiving <20 Gy correlated to WCC and ANC with an increase of 100 cc being associated with an increase of 0.4 and 0.3 respectively. CONCLUSION: The effect of concurrent chemoradiation in suppression of active bone marrow is seen in on-treatment FDG PETCT scans. Chemotherapy appears well tolerated after 2 weeks of treatment.

High Signal in Bone Marrow on Diffusion-Weighted Imaging of Female Pelvis: Correlation With Anemia and Fibroid-Associated Symptoms.

BACKGROUND: The diffusion-weighted imaging (DWI) signals of the female pelvic bone marrow show great variability and are usually high in female patients with fibroid-associated symptoms and anemia. PURPOSE: To ascertain clinical factors contributing to high signal intensity in the bone marrow of the female pelvis on DWI. STUDY TYPE: Retrospective case-control study. SUBJECTS: A single-institution review of 221 female patients underwent a pelvic magnetic resonance study from December 2012 to July 2014. FIELD STRENGTH/SEQUENCE: 1.5T/DWI (b = 0 and 1000) and apparent diffusion coefficient (ADC). ASSESSMENT: The ADC of pelvic bone marrow and the muscle-normalized signal intensity (SI) on DWI (mnDWI) were measured. A brightness grading scale ranging from 0 to 4 was used for pelvic bone assessment. Clinical factors, namely, age, the lowest hemoglobin level in the last 6 months, the presence of large uterine fibroids, and/or adenomyosis and fibroid-associated symptoms were recorded. STATISTICAL TESTS: The relationships between the brightness grade and clinical factors were evaluated through multinomial logistic regression, and correlations of mnDWI and the ADC with the clinical factors were analyzed through the Kruskal-Wallis test, Jonckheere's trend test, and the Mann-Whitney U-test with Bonferroni correction. RESULTS: Age and the hemoglobin level were inversely associated with the bone marrow brightness grade on DWI (both P < 0.05), whereas the presence of fibroid-associated symptoms showed a positive association (P = 0.028). The ADC and mnDWI in women younger than 50 years were significantly higher than those in older women (both P < 0.0001). The ADC had no significant correlation with anemia (P = 0.511), whereas mnDWI increased as the severity of anemia increased (P = 0.00154). DATA CONCLUSION: Our study showed an association of high DWI SI of pelvic bone marrow with anemia in premenopausal women. LEVEL OF EVIDENCE: 4 Technical Efficacy Stage 3 J. Magn. Reson. Imaging 2018;48:1024-1033.

Proton Therapy Reduces Normal Tissue Dose in Extended-Field Pelvic Radiation for Endometrial Cancer.

PURPOSE: We dosimetrically compared pencil beam scanning (PBS) proton therapy and intensity-modulated radiation therapy (IMRT) for pelvic and para-aortic lymph node disease in endometrial carcinoma and present acute toxicities associated with extended-field PBS. PATIENTS AND METHODS: Twenty-five patients with locally advanced endometrial malignancies were enrolled in an image-guided registry study. Seven of these patients were treated with PBS, and 18 patients were treated with IMRT. Organs at risk included pelvic bone marrow (PBM), small bowel (SB), large bowel (LB), rectum, bladder, and kidneys. The IMRT and PBS dosimetric parameters were compared using Wilcoxon rank-sum tests. RESULTS: Compared with IMRT PBM dose-volume histograms, PBS resulted in significantly lower dose volumes from 0 to 26.0 Gy (P < .05) and higher dose volumes from 33.9 to 42.9 Gy (P < .05). Overall, PBS resulted in 22% lower median PBM volume irradiated to 10 Gy (RBE) (PBS 71.3% versus IMRT 93.4%, P < .001) and 14% lower median volume irradiated to 20 Gy (RBE) (PBS 65.1% versus IMRT 79.4%, P < .001). Compared with IMRT, PBS also significantly reduced SB dose volumes from 0 to 27.5 Gy, LB dose volumes from 0 to 31.6 Gy, bladder dose volumes from 0 to 27.3 Gy, and rectal dose volumes from 0 to 7.6 Gy (all P < .05). However, PBS resulted in higher rectal dose volumes compared with IMRT from 26.0 to 48.4 Gy. Grade 3+ hematologic toxicities were present in 2 (11%) IMRT-treated patients and no PBS-treated patients. No grade 3+ gastrointestinal or genitourinary toxicities were present in either treatment group. CONCLUSION: In endometrial carcinoma, extended-field PBS is clinically feasible, resulting in statistically significant dose reduction to PBM as well as SB, LB, and bladder in the lower dose regions.

Research progress in effect of pelvic bone marrow-sparing intensity-modulated radiotherapy on hematologic toxicity in pelvic tumor patients after concurrent chemoradiotherapy / 中华放射肿瘤学杂志

Concurrent chemoradiotherapy can improve the survival rate in patients with advanced pelvic tumors.However,it also increases the incidence of hematologic toxicity and other adverse events.Patients cannot tolerate these adverse events and discontinue the therapy.Pelvic bone marrow-sparing intensity-modulated radiotherapy (PBMS-IMRT) possesses obvious advantages in reducing the radiation dose and volume of the pelvic bone marrow.In this article,comparison between PBMS-IMRT and other irradiation therapies,correlation between dosimetric parameters and hematologic toxicity and imaging methods with precise delineation of the active bone marrow were reviewed.

Association between dose-volume parameters and acute bone marrow suppression in rectal cancer patients treated with concurrent chemoradiotherapy.

Concurrent chemoradiotherapy is one of the main treatments for rectal cancer. Bone marrow suppression is one of the critical factors that affect the progress of radiotherapy. We aimed to explore the association of incidence of acute bone marrow suppression with dose-volume parameters of pelvic bone marrow among rectal cancer patients with concurrent chemoradiotherapy. We retrospectively analyzed 50 rectal cancer patients for multivariate logistic regression analyses. Three subdomains of pelvic bone marrow (PBM), bilateral ilium (IBM), lower pelvis (LPBM), and lumbosacral spine (LSBM) were assigned. The radiation dose-volume parameters from the three subdomains and the whole pelvis were evaluated. Compared to Grade 0-1 leukopenia patients, ≥Grade 2 leukopenia patients exhibited significantly higher levels of IBM V20, V25, V35, mean dose (Dmean), LPBM V20, V25, V30, LSBM V15, PBM V15, V20, and PTV. The PBM V20 of ≥Grade 2 neutropenia patients was significantly higher than that of Grade 0-1 neutropenia patients. Multivariate analysis have demonstrated that IBM V20 and LSBM V15 were the independent factors affecting ≥ Grade 2 leukopenia. There is a correlation between low dose-volume parameters with acute bone marrow suppression. IBM V20, LSBM V15 and PBM V20 can be employed as the predictors of acute bone marrow suppression.

Modeling early haematologic adverse events in conformal and intensity-modulated pelvic radiotherapy in anal cancer.

BACKGROUND AND PURPOSE: To determine if there are differences between dose to pelvic bone marrow (PBM) using intensity modulated radiotherapy (IMRT) under UK guidance versus conformal radiotherapy (CRT) per ACT II protocol and if differences translate to rates of early haematological adverse events grade 3 or greater (HT3+). METHODS AND MATERIALS: Two groups of 20+ patients, treated under IMRT and CRT regimes respectively, were identified. All patients underwent weekly blood cell count: haemoglobin (HgB), white cell count (WCC), absolute neutrophil count (ANC) and platelets (plats). Percent volume of PBM and sub structures receiving 5-25 Gy were tested for statistical significance. Regression models were used to test for correlation to blood counts. NTCP modeling was also performed. RESULTS: PMB dose metrics showed a significant increase in the IMRT group. Regression analysis showed iliac and lumbosacral PBM dose metrics to associate with reduced nadir ANC and WCC. NTCP at HT3+ was 0.13 using IMRT relative to 0.07 using CRT (p<0.05). CONCLUSION: Whilst this is a relatively small retrospective study and lacks information on the distribution of active PBM, IMRT treatment has been shown to significantly increase PMB irradiation. PBM dose metrics have been shown to be predictive of WCC and ANC suppression. NTCP modeling predicts much high risk of HT3+. Paradoxically, actual rates of HT3+ were comparable suggesting that differences in the distributions of dose metrics maybe a significant factor and/or that there are insufficiency in the NTCP modeling.