Hematologic Toxicity In Patients Research Articles

Exploring the effect of BRCA1/2 status on chemotherapy-induced hematologic toxicity in patients with ovarian cancer.

BRCA1/2 are integral to the DNA repair mechanism and their germline pathogenic variants (gBRCA) result in a high risk for developing breast and ovarian cancer. Patients with gBRCA mutations showed increased sensitivity to DNA cross-linking agent but might have increased treatment-related toxicities. Thus, we hypothesized that gBRCA mutation ovarian cancer patients who underwent platinum-based chemotherapy might be at higher risk of developing chemotherapy-induced hematologic toxicity. This study enrolled 160 patients with ovarian cancer who received frontline platinum-based chemotherapy between 2011 and 2019 in Kyungpook National University Chilgok Hospital. Incidence rate and severity of chemotherapy-induced hematologic toxicity (neutropenia, anemia, thrombocytopenia) was compared for BRCA mutation and wild patients. 160 women, including 62 BRCA1/2 (38 BRCA1, and 25 BRCA2) mutation group, and 98 noncarriers, were analyzed. A higher frequency of G2 anemia was noted in the BRCA -mutant group (22% vs. 1%, p = 0.07). Furthermore, G3 anemia was significantly common among BRCA group (12.9% vs. 3%, p = 0.02). In the subgroup analysis according to BRCA1/2 status, BRCA1 mutated patients showed a significantly higher frequency of G1 anemia than BRCA2 (89% vs. 60%, p = 0.01). In terms of neutropenia and thrombocytopenia, BRCA mutated patients and noncarriers had similar hematologic toxicity. Germline BRCA mutations were associated with a higher frequency of G2/3 anemia in ovarian cancer patients who underwent first-line platinum-based chemotherapy. Moreover, the BRCA1 mutation appeared to be more strongly associated with the incidence of chemotherapy-induced anemia. Our findings warrant further investigation in larger, prospective studies to confirm these current findings and determine whether preventive interventions may be necessary.

Hypomethylating agents are associated with high rates of hematologic toxicity in patients with secondary myeloid neoplasms developing after acquired aplastic anemia.

Not available.

SPECT/CT Image-Derived Absorbed Dose to Red Marrow Correlates with Hematologic Toxicity in Patients Treated with [177Lu]Lu-DOTATATE.

Hematologic toxicity, although often transient, is the most common limiting adverse effect during somatostatin peptide receptor radionuclide therapy. This study investigated the association between Monte Carlo-derived absorbed dose to the red marrow (RM) and hematologic toxicity in patients being treated for their neuroendocrine tumors. Methods: Twenty patients each receiving 4 treatment cycles of [177Lu]Lu-DOTATATE were included. Multiple-time-point 177Lu SPECT/CT imaging-based RM dosimetry was performed using an artificial intelligence-driven workflow to segment vertebral spongiosa within the field of view (FOV). This workflow was coupled with an in-house macroscale/microscale Monte Carlo code that incorporates a spongiosa microstructure model. Absorbed dose estimates to RM in lumbar and thoracic vertebrae within the FOV, considered as representations of the whole-body RM absorbed dose, were correlated with hematologic toxicity markers at about 8 wk after each cycle and at 3- and 6-mo follow-up after completion of all cycles. Results: The median of absorbed dose to RM in lumbar and thoracic vertebrae within the FOV (D median,vertebrae) ranged from 0.019 to 0.11 Gy/GBq. The median of cumulative absorbed dose across all 4 cycles was 1.3 Gy (range, 0.6-2.5 Gy). Hematologic toxicity was generally mild, with no grade 2 or higher toxicity for platelets, neutrophils, or hemoglobin. However, there was a decline in blood counts over time, with a fractional value relative to baseline at 6 mo of 74%, 97%, 57%, and 97%, for platelets, neutrophils, lymphocytes, and hemoglobin, respectively. Statistically significant correlations were found between a subset of hematologic toxicity markers and RM absorbed doses, both during treatment and at 3- and 6-mo follow-up. This included a correlation between the platelet count relative to baseline at 6-mo follow up: D median,vertebrae (r = -0.64, P = 0.015), D median,lumbar (r = -0.72, P = 0.0038), D median,thoracic (r = -0.58, P = 0.029), and D average,vertebrae (r = -0.66, P = 0.010), where D median,lumbar and D median,thoracic are median absorbed dose to the RM in the lumbar and thoracic vertebrae, respectively, within the FOV and D average,vertebrae is the mass-weighted average absorbed dose of all vertebrae. Conclusion: This study found a significant correlation between image-derived absorbed dose to the RM and hematologic toxicity, including a relative reduction of platelets at 6-mo follow up. These findings indicate that absorbed dose to the RM can potentially be used to understand and manage hematologic toxicity in peptide receptor radionuclide therapy.

Visceral obesity and sarcopenia as predictors of efficacy and hematological toxicity in patients with metastatic breast cancer treated with CDK 4/6 inhibitors.

We aimed to investigate whether visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and skeletal muscle area (SMA) index are predictive for efficacy and hematological toxicity in ER+HER2-metastatic breast cancer (BC) patients who received CDK 4/6 inhibitors. This retrospective cohort study analyzed 52 patients who were treated with CDK 4/6 inhibitors between January 2018 and February 2021. The values of VAT, SAT, SMA indices and hematological parameters were noted before the start, at the third and sixth months of this treatment. The skeletal muscle area (SMA) and adipose tissue measurements were calculated at the level of the third lumbar vertebra. A SMA-index value of <40cm2/m2 was accepted as the threshold value for sarcopenia. Patients with sarcopenia had a worse progression-free survival (PFS) compared to patients without sarcopenia (19.6 vs. 9.0months, p=0.005). Patients with a high-VAT-index had a better PFS (20.4 vs. 9.3months, p=0.033). Only the baseline low-SMA- index (HR: 3.89; 95% CI: 1.35-11.25, p=0.012) and baseline low-VAT-index (HR: 2.15; 95% CI: 1.02-4.53, p=0.042) had significantly related to poor PFS in univariate analyses. The low-SMA-index was the only independent factor associated with poor PFS (HR: 3.99; 95% CI: 1.38-11.54, p=0.011). No relationship was observed between body composition parameters and grade 3-4 hematological toxicity. The present study supported the significance of sarcopenia and low visceral adipose tissue as potential early indicators of poor PFS in patients treated with CDK 4/6 inhibitors.

Effect of Pneumocystis jirovecii pneumonia prophylaxis on hematologic toxicity in patients receiving chemoradiation for primary brain tumors.

Diffuse gliomas are managed with radiation and temozolomide; however, this therapy often results in hematologic toxicities. Patients undergoing chemoradiation also risk contracting Pneumocystis jirovecii pneumonia (PJP), and frequently receive prophylaxis against PJP during treatment. Independent of chemoradiation, some PJP prophylaxis drugs have the potential to cause myelosuppression, which could require cessation of chemotherapy. Here, we evaluate differences in the frequency of hematologic toxicities during chemoradiation when patients receive PJP prophylaxis. This retrospective chart review evaluated patients with primary brain tumors treated with radiation and concurrent temozolomide. Analyses were performed to assess the effect of the type of PJP prophylaxis on risk for neutropenia, lymphopenia, or thrombocytopenia and the severity of these adverse effects as defined using the Common Terminology Criteria for Adverse Events. Of the 217 patients included in this analysis, 144 received trimethoprim-sulfamethoxazole (TMP/SMX) and 69 received pentamidine. Of the patients who received TMP/SMX, 15.3% developed an absolute neutrophil count < 1500 cells/µL compared with 7.2% of patients receiving pentamidine (p = 0.10). Platelet count < 100,000/µL occurred in 18.1% of patients who received TMP/SMX and 20.3% of patients who received pentamidine (p = 0.70). No significant differences in lymphocyte counts between therapies were seen. Severity of hematologic toxicities were similar between PJP prophylaxis groups. These findings suggest that the type of PJP prophylaxis does not significantly affect the risk for hematologic toxicity in brain tumor patients receiving radiation and temozolomide. Additional studies are merited to evaluate the higher rate of neutropenia in patients on TMP/SMX observed in this study.

Assessment of hematological toxicity in patients with advanced neuroendocrine tumors and extensive/innumerable bone metastases undergoing lutetium-177 DOTATATE treatment.

592 Background: The introduction of peptide receptor radionuclide therapy (PRRT) using Lutetium-177 (177Lu) DOTATATE has led to a paradigm shift in the treatment of neuroendocrine tumors (NETs). Hematological toxicity is a well-recognized adverse effect (AE) of 177Lu DOTATATE. Most cytopenias are transient, with an estimated incidence of 10-25%, typically mild to moderate in severity (grade G1-2). The most dreaded AE of PRRT is therapy-related myeloid neoplasm (t-MN), with an estimated 2-8% incidence and a higher incidence reported in patients who also received prior chemotherapy. We sought to evaluate the hematological safety of 177Lu PRRT in the setting of NETs with extensive (i.e., innumerable) bone metastases. Methods: We retrospectively reviewed the medical records of all Mayo Clinic patients (pts) with extensive/innumerable osseous metastases, defined as &gt;50% skeletal involvement by positron emission tomography (PET) DOTATATE, who were treated with 177Lu DOTATATE. Pts characteristics and laboratory results were collected before, during, and after 177Lu DOTATATE treatment. Hematotoxicity was graded according to the NCI-CTCAE v5. Results: Out of 27 pts, 13(48%) developed cytopenia(s) of any grade after treatment with one or more cycles of 177Lu DOTATATE. In total, there were 13(48%) pts with anemia, 13(48%) with thrombocytopenia, and 6(22%) with neutropenia. Six (22%) pts had severe hematological toxicity (G3-4). Twelve months post-PRRT, 7(26%) pts continued to experience cytopenia(s) of any grade, of whom 4(15%) had G3-4 hematotoxicity. One pt developed t-MN, and two pts had myelophthisis on bone marrow biopsy from infiltrating NET. 16(59%) pts received cytotoxic chemotherapy before PRRT, and 7(25.9%) developed subsequent cytopenia(s). Overall, 15(55%) pts completed four cycles, while 3 pts didn’t complete four cycles of 177Lu DOTATATE due to hematotoxicity. Conclusions: Pts with advanced NETs and extensive/innumerable bone metastases treated with PRRT could be at higher risk for myelosuppression than historical controls. Our study highlights the importance of carefully monitoring and assessing hematological parameters in pts being considered for 177Lu DOTATATE with extensive/innumerable bone metastasis. [Table: see text]

Postradiation platinum-etoposide in adult medulloblastomas: retrospective analysis of hematological toxicity.

Aim: Adult medulloblastomas (MB) are rare, and optimal post-craniospinal irradiation (CSI) chemotherapy is not yet defined. We investigated hematological toxicity in patients treated with platinum-etoposide (EP) post-CSI. Methods: Retrospective, single-institution study to determine hematological toxicity in adult MB patients treated with EP (1995-2022). Results: Thirteen patients with a median follow-up of 50months (range, 10-233) were analyzed. Four discontinued treatment due to toxicity, one after 1, 3 after 3 cycles. Hematological toxicities included grade 3 (5 patients) and grade 4 (6 patients). Two patients experienced post-treatment progression and died 16 and 37months from diagnosis. Conclusion: Post-CSI EP demonstrates acceptable hematological toxicity in adult MB. However, the small cohort precludes definitive survival outcome conclusions. Prospective studies for comprehensive comparisons with other regimens are needed in this context.

Hypomethylating Agents Are Associated with High Rates of Hematologic Toxicity in Patients with Secondary MDS/AML That Develops after Acquired Aplastic Anemia

Acquired aplastic anemia (AA) is an autoimmune bone marrow failure (BMF) associated with depletion of hematopoietic stem and progenitor cells. Approximately 15-20% of AA patients treated with immunosuppressive therapy (IST) develop late complications of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Little is known about managing patients with post-AA myeloid neoplasms (MN). We hypothesized that patients with post-AA MN may be particularly susceptible to hematologic toxicities from cytotoxic therapy because of stem cell deficits. To investigate our hypothesis, we retrospectively analyzed post-AA MN patients treated at our 2 institutions over the past 15 years. Fourteen post-AA MN patients were identified: 11 with MDS, 1 with AML, and 2 with clonal cytopenia of undetermined significance (CCUS). Patients with inherited BMF or allogeneic stem cell transplant (SCT) prior to MN diagnosis were excluded. The median age at MN was 56.5 years (range 5-75) with a median time of 5 years (range 0.25-30) between AA diagnosis and MN. At MN diagnosis, 12 of 14 patients (86%) had a partial or complete response of AA with 5 receiving cyclosporine (CSA) maintenance. Two patients (14%) were on CSA within 6 months of IST without response. After MN diagnosis, CSA was discontinued. Ten adults received hypomethylating agents (HMA) as first-line treatment in preparation for SCT. Three pediatric patients were treated with SCT with no prior HMA. One patient died before receiving treatment. The 10 post-AA patients who received HMA were matched in a 3:1 ratio with a similarly aged, randomly selected non-AA MDS cohort treated with HMA at our center during the same period (Table 1). Compared to patients with non-AA MDS, post-AA MN patients tolerated HMA poorly with frequent, severe complications. Their median per-cycle duration of grade 4 neutropenia was longer (9 v. 1.5 days, p = 0.044), as was median duration of grade 4 thrombocytopenia (13 v. 0 days, p = 0.003). Post-AA patients notably had lower baseline platelets prior to HMA (median 36.5 v. 115 k/mL, p =0.007). Following HMA, the post-AA cohort had higher rates of febrile neutropenia (80% v. 17%, RR 4.8, p &amp;lt; 0.001) and infections ≥ grade 3 (90% v. 13%, RR 6.8, p &amp;lt; 0.001). They also had higher rates of ≥ grade 3 bleeding (40% v. 7%, RR 6.0, p = 0.026) with 2 patients (20%) experiencing intracranial hemorrhage on HMA; no such events occurred in the non-AA cohort. Post-AA patients had more hospital admissions - 18 in 25 total chemotherapy cycles (72%) compared to 12 in 207 cycles (6%) in the matched cohort (RR 12.4, p &amp;lt; 0.001). Post-AA MN patients had more treatment delays &amp;gt;2 weeks (28% v. 8% of planned treatment cycles, RR 3.4, p = 0.01) and dose reductions (40% v. 13%, RR 3.0, p = 0.089). HMA was discontinued due to treatment-emergent adverse events (TEAEs) in 70% of post-AA cases v. 3% of non-AA patients (RR 21.0, p &amp;lt; 0.001). Consequently, post-AA MN patients received fewer cycles of HMA compared to non-AA patients (median 2.5 v. 6, p = 0.021). Death occurred following TEAEs in 20% of post-AA MN patients; no deaths on HMA occurred in the non-AA cohort (RR 14.1, p = 0.058). Among surviving patients, SCT was delayed in 20% of the non-AA cohort due to TEAEs, while no delays occurred in the matched cohort. The median months from final chemotherapy cycle to SCT were 4 (range 1-12) in post-AA v. 1 (1-3) in non-AA, while median months from MN diagnosis to SCT were 8.5 (4-21) in post-AA v. 5 (4-15) in non-AA. For all 14 post-AA MN patients, including those not treated with HMA, overall survival (OS) from MN diagnosis was 71% (95% CI 51-99) at 1 year and 56% (95% CI 34-90) at 3 years. OS of post-AA MN patients differed significantly (p = 0.011) based on treatment with SCT. Among the 5 who did not receive SCT, 4 died within 3 years of MN, while 1 patient is alive 13 months from diagnosis receiving supportive care after intracranial hemorrhage during the first cycle of HMA. In contrast, 7 of 9 (78%) patients who received SCT were alive 3 years after MN diagnosis. Of the 6 patients treated with SCT after HMA, 5 stopped HMA due to toxicity, all had morphologic dysplasia at SCT, and 2 were transplanted with ≥ 5% marrow blasts. Our study shows that patients with MN following antecedent autoimmune AA are at high risk of severe toxicities with standard HMA regimens and have difficulty tolerating repeated cycles. Our results do not support routine use of HMA prior to SCT in this patient population and suggest that early SCT may be the most suitable strategy.

RADT-27. BONE MARROW SUPPRESSION AFTER REIRRADIATION THERAPY WITH PROTON VERSUS PHOTON THERAPY FOR RECURRENT GLIOMA

Abstract INTRODUCTION High grade radiation-induced lymphopenia has been implicated to worse prognostic outcomes and overall survival in numerous malignancies. Understanding factors which influence lymphopenia can help optimize radiation delivery and overall patient care. Proton therapy (PRT), due to its distinct dose fall-off, spares tissues and organ-contained blood pools from excess radiation compared to conventional photon radiation (XRT) and may thereby reduce hematologic toxicity. METHODS Patients with confirmed glioma diagnosis who underwent reirradiation with either PRT or XRT were retrospectively analyzed. Complete blood counts (CBCs) within one month of reirradiation start, and CBCs within one month of reirradiation completion were reviewed. Values of interest included total white blood cell (WBC), absolute neutrophil count (ANC), and absolute lymphocyte count (ALC). Dosimetric data was collected to assess whole brain mean dose (WBMD), and volume of brain tissue receiving 5-50 Gy (V5-V50). RESULTS 16 patients receiving either PRT (n = 8) or XRT (n = 8) were included. Treatment doses ranged from 35-59.4 Gy. Across all patients there was a decrease in WBC, ANC, and ALC after reirradiation in both PRT and XRT (p &amp;lt; 0.05). Compared to reirradiation with XRT, patients who underwent PRT had significantly lesser reductions in WBC (PRT: 8.60% decrease, XRT: 22.58% decrease; p &amp;lt; 0.05). PRT reirradiation also resulted in lesser ANC and ALC reductions, though did not reach statistical significance. On dosimetric comparison of XRT and PRT plans, PRT demonstrated significant reductions in V5, V10, V20, and V30 (p &amp;lt; 0.05). V5 through V40 and WBMD were significantly correlated with decreased WBC, ANC, and ALC (p &amp;lt; 0.01). CONCLUSION Preliminary results show PRT reirradiation leads to decreased WBMD and volumes of brain tissues receiving 5 to 30 Gy. Given that these parameters are associated with greater reductions in lymphocytic counts, PRT reirradiation may confer reduced hematologic toxicity in patients seeking adjuvant radiation therapy.

1601P Relationship between CT and ultrasonography-based sarcopenia and hematologic toxicity in patients with cancer receiving chemotherapy

1601P Relationship between CT and ultrasonography-based sarcopenia and hematologic toxicity in patients with cancer receiving chemotherapy

WBRT is Associated with Higher Rates of Hematologic Toxicity than Stereotactic Radiosurgery in Brain Metastasis Patients

Whole brain radiotherapy (WBRT) has historically been a standard of care in patients with multiple brain metastases. Studies show that WBRT may be associated with a transient detriment in hematological parameters because of exposure to a larger proportion of circulating lymphocytes, platelets and hematopoietic cells within the bone marrow of the cranium. In this study, we tested the hypothesis that stereotactic radiotherapy (SRS) may cause reduced hematologic toxicity in patients compared to WBRT. We retrospectively identified 100 patients treated for brain metastasis, with either SRS or WBRT from 2016 to 2019, and queried their pre- and post-treatment hematological parameters including hemoglobin, total white blood cell (WBC), absolute neutrophil count (ANC), absolute lymphocyte count, and platelet count. CTCAE v5.0 was used for grading hematologic toxicities. Serial values were compared by treatment type and controlled for age, gender, and systemic therapy. Student t-test was used for intergroup comparison and p-value <0.05 was considered significant. Of 100 patients, median brain metastases was 3 (range 1-22), 51 received SRS and 49 received WBRT. We observed that patients treated with WBRT had a significantly higher post-treatment reduction in platelet count (-51.2 vs 9.8; p = 0.001) and higher incidence of any grade thrombocytopenia (31.2% vs 10%; p = 0.019) compared to patients treated with SRS. We also noted that compared with SRS, WBRT was associated with a higher post-treatment reduction in circulating lymphocytes (-0.80 vs 0.14; p = 0.071) and higher incidence of G3+ lymphopenia (43.2% vs 22.2%; p = 0.07). Numerical incidence of any G3+ hematological toxicity was also higher in the WBRT group but the difference was not statistically significant (40% vs 28%, p = 0.162). Hemoglobin count, WBC, and ANC were not meaningfully different pre- and post-treatment for either group. WBRT results in an increased amount and duration of radiation exposure to circulating intracranial blood volume. In our study, patients treated with WBRT experienced higher rates of clinically significant lymphopenia & thrombocytopenia compared to patients treated with SRS. In addition to the cognitive benefits of SRS compared to WBRT, there may be significant hematologic benefits as well. Further studies are warranted to clarify and validate these findings.

Active bone marrow-sparing to reduce the incidence of grade 3+ acute hematologic toxicity in patients with locally advanced cervical cancer who receive chemoradiotherapy: A single-center prospective randomized controlled trial.

5524 Background: Acute haematologic toxicity is the most common side effect of chemoradiotherapy in patients with locally advanced cervical cancer .We aim to test the efficacy of single-photon emission computed tomography-defined active bone marrow-sparing volumetric-modulated arc therapy in reducing grade 3+ acute hematologic toxicity (HT) in locally advanced cervical cancer patients treated with chemoradiotherapy. Methods: This was a prospective, single-center, open label, randomized clinical trial that enrolled locally advanced cervical cancer patients. Participants were randomized to the 99mTc sulfur colloid SPECT-defined ABMS VMAT (ABMS group) or control group, who received weekly cisplatin concurrently with volumetric-modulated arc therapy followed by high-dose-rate intracavitary brachytherapy. The ABMS group additionally received SPECT-defined ABM dose constraints. The primary endpoint was the incidence of grade 3+ acute hematologic toxicity.Secondary objectives included acute gastrointestinal toxicity, planning Target Volume (PTV) coverage, dosimetric parameters of organs at risk (OARs), progression-free survival (PFS), overall survival (OS). Results: A total of 192 FIGO stage IB-IIIB patients were randomized treated (96 each in the ABMS control groups). The median follow-up was 24.0 months. The incidence of grade 3+ acute hematologic toxicity in the ABMS group was significantly lower than that in the control group (32.3% vs 53.1%, p&lt;0.01). The number of patients completing five cycles of cisplatin was 88.5% in the ABMS group and 75% in the control group, and the difference was significant (p=0.02). There were no significant differences in the mean dose to 95%, 97% and 99%of the PTV between the ABMS group (45.1 Gy, 44.6 Gy, and 43.3 Gy, respectively) and the control group (45.4 Gy, 44.8 Gy, and 43.6 Gy). There were no differences in dosimetric parameters of OARs ,acute gastrointestinal toxicity, 2-year PFS or 2-year OS between the two groups. Patients in the control group had nonsignificantly worse 2-year distant metastasis than patients in the ABMS group (17.8% vs. 11.1%, p=0.19). Conclusions: ABMS VMAT significantly reduced grade 3+ acute HT and improved chemotherapy delivery compared with the control treatment. We found weak evidence of the effect of ABMS VMAT on distant metastasis. Clinical trial information: ChiCTR-IOR-16010214 .

Rates of hematologic toxicity in WBRT vs SRS.

e14014 Background: Whole brain radiotherapy (WBRT) has historically been a standard of care in patients with multiple brain metastases. Studies show WBRT may be associated with a transient detriment in hematological parameters because of exposure to a larger proportion of circulating lymphocytes, platelets and hematopoietic cells within the bone marrow of the cranium. We tested the hypothesis that stereotactic radiotherapy (SRS) has reduced hematologic toxicity in patients compared to WBRT. Methods: We retrospectively identified 100 patients treated for brain metastasis, with either SRS or WBRT from 2016 to 2019, and queried their pre- and post-treatment hematological parameters including hemoglobin, total white blood cell (WBC), absolute neutrophil count (ANC), absolute lymphocyte count, and platelet count. CTCAE v5.0 was used for grading hematologic toxicities. Serial values were compared by treatment type and controlled for age, gender, &amp; systemic therapy. Student t-test was used for intergroup comparison and p-value &lt;0.05 was considered significant. Results: Of 100 patients, median brain metastases was 3 (range 1-22), 51 received SRS and 49 received WBRT. We observed that patients treated with WBRT had a significantly higher post-treatment reduction in platelet count (-51.2 vs 9.8; p=0.001) and higher incidence of any grade thrombocytopenia (31.2% vs 10%; p=0.019) compared to patients treated with SRS. We also noted that compared with SRS, WBRT was associated with a higher post-treatment reduction in circulating lymphocytes (-0.80 vs 0.14; p = 0.071) and higher incidence of G3+ lymphopenia (43.2% vs 22.2%; p=0.07). Numerical incidence of any G3+ hematological toxicity was also higher in the WBRT group but the difference was not statistically significant (40% vs 28%, p=0.162). Hemoglobin count, WBC, and ANC were not meaningfully different pre- and post-treatment for either group. Conclusions: WBRT results in an increased amount and duration of radiation exposure to circulating intracranial blood volume. In our study, patients treated with WBRT experienced higher rates of clinically significant lymphopenia &amp; thrombocytopenia compared to patients treated with SRS. In addition to the cognitive benefits of SRS compared to WBRT, there may be significant hematologic benefits as well. Further studies are warranted to clarify and validate these findings. [Table: see text]

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

PurposeThis 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. MethodsA 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). ResultsThe 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. ConclusionThe 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.

Predicting subacute hematological toxicity of 177Lu-DOTATATE therapy using healthy organs' uptake on post-treatment quantitative SPECT: A pilot study.

The aim is to investigate the usefulness of 177Lu-DOTA-0-Tyr3-Octreotate (DOTATATE) healthy organs' (spleen, kidneys, bone marrow) standard uptake value for the prediction of subacute hematological toxicity in patients undergoing 177Lu-DOTATATE treatment. All patients referred from January 2021 to May 2022 for 177Lu-DOTATATE treatment were retrospectively screened. For each treatment session, baseline clinical data including age, sex, weight, delay between 177Lu-DOTATATE treatment and last cold somatostatin analogue intake were collected. Mean standardized uptake value (SUVmean) of healthy organs was measured and analyzed by generalized linear mixed effect models. Outcomes (significant decrease of platelets, hemoglobin levels and neutrophils) were assessed 1 month later, considering their within-subject biological coefficient of variation, published by the European Federation of Clinical Chemistry and Laboratory Medicine. A total of 9 patients (33 treatment sessions) were included. No predictive factors were identified for platelet and neutrophil decrease. Splenic SUVmean was found to be a significant predictor of hemoglobin levels decrease. Using an optimal threshold of ≥6.22, derived sensitivity and specificity to predict hemoglobin decrease were 85.7% [46.4; 99.0] and 76.9% [57.5; 89.2] respectively with an accuracy of 82.4%. Although not significantly predictive of hematological toxicity, bone marrow SUVmean and renal SUVmean were correlated with splenic SUVmean. Quantitative single photon emission computed tomography and healthy organs analysis might help to foresee hematological subacute toxicity in patients undergoing 177Lu-DOTATATE treatment and improve patient management.

Safety of linezolid in patients with decreased renal function and trough monitoring: a systematic review and meta-analysis

BackgroundLinezolid causes hematological toxicity, mostly thrombocytopenia, which leads to treatment discontinuation and failure. Recent studies revealed that during linezolid therapy, the incidence of treatment-related hematological toxicity is significantly higher in patients with decreased renal function (DRF) than in those with normal renal function. Linezolid monitoring is necessary due to the high frequency of hematological toxicity in patients with DRF and the relationship between blood concentration and safety. We performed a systematic review and meta-analysis to evaluate the safety correlation between DRF and trough monitoring.MethodsArticles published before June 24, 2022, on MEDLINE, Web of Sciences, Cochrane Register of Controlled Trials, and ClinicalTrials.gov were systematically analyzed. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the Mantel–Haenszel method and the variable effects model.ResultsThe incidence of hematological toxicity was significantly higher in patients with DRF than in those without DRF (OR = 2.37; p < 0.001). Subgroup analysis, performed according to hematotoxicity classification, including thrombocytopenia, anemia, and pancytopenia, revealed a significantly higher incidence of thrombocytopenia (OR = 2.45; p < 0.001) and anemia (OR = 2.31; p = 0.006) in patients with DRF than in those without; pancytopenia (OR = 1.41; p = 0.80) incidences were not significantly higher. Based on a systematic review, linezolid trough concentrations > 6–7 μg/mL may be associated with an increased incidence of thrombocytopenia. However, no confidential threshold values for the development of thrombocytopenia were found in the area under the concentration curve values for children or adults.ConclusionWe observed a high frequency of hematological toxicity during linezolid therapy in patients with DRF. To ensure safety, linezolid trough concentrations should be ≤6–7 μg/mL.

NCOG-21. EFFECT OF PNEUMOCYSTIS JIROVECII PNEUMONIA PROPHYLAXIS ON HEMATOLOGIC TOXICITY IN PATIENTS RECEIVING CHEMORADIATION FOR PRIMARY BRAIN TUMORS

Abstract INTRODUCTION Management of diffuse gliomas often includes radiation plus concomitant and adjuvant temozolomide. Hematologic toxicities are common from this therapy. Patients frequently receive prophylaxis against pneumocystis jirovecii pneumonia (PJP) during chemoradiation; however, some PJP prophylaxis drugs have the potential to independently cause myelosuppression which could exacerbate the hematologic toxicities from chemoradiation requiring chemotherapy dose reduction or cessation. We seek to understand differences in the frequency of hematologic toxicities during chemoradiation when either trimethoprim/sulfamethoxazole (TMP/SMX) or pentamidine are used for PJP prophylaxis. METHODS This was a retrospective chart review of patients with primary brain tumors who were treated with first-time radiation and concurrent temozolomide between April 2014-August 2021 at the Huntsman Cancer Institute. Chi squared analysis was used to evaluate effect of choice of PJP prophylaxis on risk for neutropenia, lymphopenia, or thrombocytopenia within one month of finishing chemoradiation. Logistic regression was performed to evaluate the effect of PJP prophylaxis on the Common Terminology Criteria for Adverse Events (CTCAE) score for the lowest neutrophil, lymphocyte, and platelet count. RESULTS 217 patients were included in analysis. 144 patients received TMP/SMX, 69 received pentamidine, 1 received dapsone, and 3 received no prophylaxis at initiation of chemoradiation. Of patients who received TMP/SMX, 15.4% developed an absolute neutrophil count &amp;lt; 1,500 cells/µL while this occurred in 7.2% of patients receiving pentamidine (p=0.10). Platelet count &amp;lt; 100,000 occurred in 18.1% of patients who received TMP/SMX and 20.3% of patients who received pentamidine (p=0.70). Worst CTCAE scores for hematologic toxicities were similar between PJP prophylaxis groups. CONCLUSION Our study provides preliminary evidence that the type of PJP prophylaxis does not appear to significantly impact risk for hematologic toxicity in patients receiving radiation and concurrent temozolomide; however, there was a trend toward higher rates of neutropenia with TMP/SMX and larger analyses are needed to further evaluate these findings.

Medication risks in older patients (70 +) with cancer and their association with therapy-related toxicity

BackgroundTo evaluate medication-related risks in older patients with cancer and their association with severe toxicity during antineoplastic therapy.MethodsThis is a secondary analysis of two prospective, single-center observational studies which included patients ≥ 70 years with cancer. The patients’ medication lists were investigated regarding possible risks: polymedication (defined as the use of ≥ 5 drugs), potentially inappropriate medication (PIM), and relevant potential drug-drug interactions (rPDDI). The risks were analyzed before and after start of cancer therapy. Severe toxicity during antineoplastic therapy was captured from medical records according to the Common Terminology Criteria for Adverse Events (CTCAE). The association between grade ≥ 3 toxicity and medication risks was evaluated by univariate as well as multivariate regression adjusted by ECOG and age.ResultsThe study cohort comprised 136 patients (50% female, mean age 77 years, 42% hematological malignancies). Before the start of cancer therapy, patients took on average 5 drugs as long-term medication and 52% of patients were exposed to polymedication. More than half of patients used at least one PIM. Approximately one third of patients exhibited rPDDI. The prevalence of medication risks increased after start of cancer therapy. rPDDI were significantly associated with severe overall toxicity (OR, 5.07; p = 0.036; 95% Confidence Interval (CI) 1.11–23.14; toxicity in patients with rPDDI 94.1% (32/34) vs 75.9% (60/79) in patients without rPDDI) and hematological toxicity (OR, 3.95; p = 0.010; 95% CI 1.38–11.29; hematological toxicity in patients with rPDDI 85.3% (29/34) vs 59.5% (47/79) in patients without rPDDI). In the multivariate analysis adjusted by ECOG and age, only the association for rPDDI with hematological toxicity remained statistically significant (OR, 4.51; p = 0.007; 95% CI 1.52–13.38). These findings should be further investigated in larger studies.ConclusionMedication risks are common in older patients with cancer and might be associated with toxicity. This raises the need for tailored interventions to ensure medication safety in this patient cohort.

Safety of temozolomide use in adult patients with renal dysfunction.

Temozolomide (TMZ), a cytotoxic DNA alkylating agent, is the main chemotherapy used for the treatment of high grade astrocytomas. The active alkylator, methylhydrazine, is not recovered in urine and thus renal function is not expected to affect clearance. Prescribing information for TMZ states pharmacokinetics have not been studied in adults with poor renal function, eGFR < 36mL/min/1.73 m2. We reviewed our clinical experience with TMZ in patients with impaired renal function to evaluate safety of administering full dose TMZ. The primary endpoint was to characterize the incidence and severity of thrombocytopenia in patients with eGFR < 60mL/min/1.73 m2 who received TMZ for treatment of high grade gliomas (HGG) or primary CNS lymphoma (PCNSL). Secondary endpoints included incidence and severity of neutropenia, lymphopenia hepatotoxicity, and number of TMZ cycles administered. Medical records of patients with HGG or PCNSL treated with TMZ from October 1, 2016-September 30, 2019 were accessed to identify cases for this study. Thirty-two patients were eligible for this study. Of the seven patients with eGFR < 36mL/min/1.73m2, 38/39 cycles (97%) were completed without grade 3-4 thrombocytopenia. No patients experienced grade 3-4 neutropenia, and grade 3-4 lymphopenia occurred in 5 cycles (15%). One patient discontinued TMZ 7days prior to completion of radiation due to thrombocytopenia. Hematologic toxicity in patients with severe renal dysfunction, eGFR < 36mL/min/1.73m2, is similar to that of patients with normal renal function. Severe renal impairment does not preclude use of temozolomide, but cautious monitoring of blood counts is warranted.

Pelvic bones ADC could help to predict severe hematologic toxicity in patients undergoing concurrent chemoradiotherapy for cervical cancer

BackgroundHematologic toxicity (HT) during concurrent chemoradiotherapy (CCRT) for cervical cancer can lead to treatment breaks and compromise efficacy. PurposeTo evaluate the association between severe hematologic toxicity (HT) and clinical factors and pelvic apparent diffusion coefficient (ADC) during CCRT of cervical cancer patients. MethodsData from 120 patients with cervical cancer who were treated with CCRT from January 2016 and December 2018 were retrospectively analyzed. The clinical data (age, menopausal status, clinical stage, body mass index, chemotherapy regimen and chemotherapy cycle) of the patients were collected, and the cohort were divided into two groups based on the HT grade: HT3+ group (HT grade ≥ 3; 66 patients) and HT3- group (HT grade<3; 54 patients). All patients performed MRI before CCRT, and pelvic (ilium, pubis, ischium) ADC value was measured on ADC map. The correlation between severe HT and clinical parameters and pelvic ADC value were analyzed by univariate analysis, and the diagnostic performance was further assessed by receiver operating characteristic (ROC) analysis. ResultsIn univariate analysis, the menopausal status (p = 0.012) and chemotherapy regimen (p = 0.011) were significantly correlated with severe HT in overall patients, and menopausal patients or patients receiving paclitaxel plus cisplatin (TP) regimen were more likely to develop severe HT. HT3+ group showed a significantly lower pelvic ADC value than HT3- group. The ADC value cut-offs derived from our study for predicting severe HT was 0.317 × 10−3 mm2/s in overall patients. Neither clinical parameters nor pelvic ADCs were associated with severe HT in menopausal patients when analyzed separately (p > 0.05). ConclusionsSevere HT was significantly associated with menopausal status and chemotherapy regimen in patients with cervical cancer treated with CCRT, and HT3+ group showed a lower pelvic ADC value.