Risk Of Treatment-related Toxicity Research Articles

Bone Mineral Density in Survivors of Childhood Cancer: A Meta-Analysis.

There is an increasing population of childhood cancer survivors (CCS) at risk for treatment-related toxicities, including skeletal morbidities. Bone mineral density (BMD) is a proxy for bone health and reductions are associated with osteoporosis and fractures. To investigate bone health in CCS by conducting a systematic review and meta-analysis of BMD after completed treatments. We searched Medline, Embase, Cochrane, and Web of Science in May 2019 and updated in May 2023. Studies reporting BMD Z-scores measured with dual-energy x-ray absorptiometry in CCS after treatment completion. We performed a pooled analysis of studies reporting BMD Z-scores and thereafter we analyzed studies comparing BMD in survivors and healthy controls. All analyses were performed based on the site of BMD measurement. Of 4243 studies, 84 were included (N = 8106). The mean time off-treatment across the studies ranged from 2 months to 24 years. The overall pooled mean Z-score was -0.57 (95% confidence interval [CI] -0.59 to -0.55) in the whole-body, -0.84 (95% CI -0.86 to -0.83) in the lumbar spine, -0.79 (95% CI -0.81 to -0.77) in the femoral neck and -0.14 (95% CI -0.18 to -0.11) in the total hip. When comparing survivors with controls, BMD was significantly lower in survivors at all sites. English publications, study-level meta-analysis. We showed a significant reduction of BMD Z-scores in CCS. Given the increased fracture risk already within -1 SD, these results emphasize the need for BMD surveillance and secondary prevention in CCS.

Decade of insights: Bleomycin-induced pneumonitis and use of G-CSF in chemotherapy-treated germ cell testicular tumors and Hodgkin lymphoma—Real-world outcomes from an academic cancer center.

e17013 Background: Bleomycin induced pulmonary toxicity (BIP) occurs in 4-10% of treated patients. Preclinical reports suggest G-CSF use may increase BIP risk, due to neutrophil migration to lung tissues. Limited real-world clinical data is available and G-CSF use may reduce risk of treatment related toxicity with curative bleomycin combination treatment. Methods: We conducted a retrospective study of patients with GCT (Germ cell tumor) and HL (Hodgkin’s lymphoma) receiving bleomycin containing chemotherapy and at-least on dose of G-CSF at The James Cancer Center from 2010-2022 using the institutional database. BIP was diagnosed mainly using clinical symptoms complemented by radiological evidence when possible. We reviewed 361 patients, 145 in GCT group and 216 in HL group and clinically relevant information was recorded.Descriptive statistics for the study variables were presented using frequencies and percentages overall. The bivariate associations between G-CSF use and clinical outcomes were assessed using chi-square tests or fisher’s exact tests for the overall sample, and by chemotherapy type. We used SPSS 26.0 for all the statistical analyses, and an alpha level of 0.05 (two-sided) was used for all the tests. Results: Data on 361 patients, including 145 GCT and 216 HL patients treated with at least one dose of bleomycin was available. The median age was 36.3 years in the GCT group and 44.2 years in the HL group.144 patients in the GCT and 50 patients in the HL group received at least 1 dose of G-CSF. BIP occurred in 4.8% in the GCT and 7.4% of patients in the HL group. Only 2 out of 16 patients developing BIP in the HL group received G-CSF. All patients with BIP developed symptomatic disease. On bivariate analysis, no association was noted between BIP and G-CSF in either group (p-value =1.00 in GCT and p-value = 0.32 in HL). Febrile neutropenia (FN) was reported in 4 patients in the GCT group and 29 in the HL group. In the HL subgroup, 28 (28/29) patients developing FN did not receive G-CSF (p-value=0.0008). All patients who developed FN required hospital admission. Conclusions: Use of G-CSF in patients receiving bleomycin was not associated with an increased incidence of BIP. Incidence of FN was higher in patients not receiving G-CSF leading to hospital admissions. [Table: see text]

Feasibility of Intraoperative Radiotherapy Tumor Bed Boost in Patients with Breast Cancer after Neoadjuvant Chemotherapy.

This study aimed to assess the feasibility and safety of administering intraoperative radiotherapy (IORT) as a boost during breast-conserving surgery (BCS) following neoadjuvant chemotherapy for patients at high risk of breast cancer recurrence. Patients who underwent neoadjuvant chemotherapy received a single 20-Gy dose of IORT during BCS, followed by external beam radiotherapy 4-6 weeks after surgery. The median follow-up duration was 31.0 months (range, 18.0-59.0 months). Initial tumor sizes had a median of 2.6 cm (range: 0.8-5.3 cm), reducing to 0.3 cm (range: 0-4.0 cm) after neoadjuvant chemotherapy. The most common neoadjuvant chemotherapy regimen was doxorubicin and cyclophosphamide, followed by paclitaxel (n=42, 73.7%). Among 57 patients who received neoadjuvant chemotherapy before BCS and IORT, 2 patients (3.5%) required secondary surgery to achieve negative resection margins due to initially positive margins. Regional lymph node irradiation was performed in 37 (64.9%) patients. There was no grade 3 or higher adverse events, with 4 patients (7.0%) experiencing grade 2 acute radiation dermatitis and 3 (5.3%) having less than grade 2 breast edema. Binary correlation analysis did not reveal statistically significant associations between applicator size or radiation therapy modality and the risk of treatment-related toxicity. Furthermore, chi-square analysis showed that the grade of treatment-related toxicity was not associated with the fractionated regimen (p=0.375). Most patients successfully received IORT as a tumor bed boost after neoadjuvant chemotherapy. Thus, IORT may be a safe and feasible option for patients with advanced-stage breast cancer receiving neoadjuvant chemotherapy.

Recent advances and future perspectives of CAR-T cell therapy in head and neck cancer.

Head and neck cancer (HNC) ranks as the sixth most prevalent type of cancer globally and accounts for about 4% of all types of cancer. Among all HNC, most are head and neck squamous cell carcinoma (HNSCC) with clinical therapies that include surgery, radiation therapy, chemotherapy, immunotherapy, targeted therapy, and multimodal treatments. In recent years, chimeric antigen receptor (CAR)-T cell immunotherapy has significantly transformed the therapeutic approaches for leukemia and lymphoma and has garnered increased attention as a potential treatment for a wide range of cancers. However, CAR-T immunotherapy in solid tumors, especially HNSCCs, lags significantly behind due to the paucity of tumor-specific antigens, high levels of tumor heterogeneity, immunosuppressive tumor microenvironment, the risk of treatment-related toxicities and off-target adverse events in HNSCCs. The objective of this review is to explore the advancement of CAR-T cell therapy in the treatment of HNSCCs. We aim to outline the targeted antigens in HNSCCs, highlight the challenges and potential solutions, and discuss the relevant combination therapies. Our review presents a comprehensive overview of the recent developments in CAR-T cell therapy for HNSCCs, and provides valuable insights into future research avenues.

Assessment of lung doses in patients undergoing total body irradiation for haematological malignancies with and without lung shielding.

Total body irradiation (TBI) practices vary considerably amongst centres, and the risk of treatment related toxicities remains unclear. We report lung doses for 142 TBI patients who underwent either standing TBI with lung shield blocks or lying TBI without blocks. Lung doses were calculated for 142 TBI patients treated between June 2016 and June 2021. Patients were planned using Eclipse (Varian Medical Systems) using AAA_15.6.06 for photon dose calculations and EMC_15.6.06 for electron chest wall boost fields. Mean and maximum lung doses were calculated. Thirty-seven patients (26.2%) were treated standing using lung shielding blocks with 104 (73.8%) treated lying down. Lowest relative mean lung doses were achieved using lung shielding blocks in standing TBI, reducing the mean lung doses to 75.2% of prescription (9.9 Gy), ±4.1% (range 68.6-84.1%) for a prescribed dose of 13.2 Gy in 11 fractions, including contributions from electron chest wall boost fields, compared to 12 Gy in 6 fraction lying TBI receiving 101.6% mean lung dose (12.2 Gy) ±2.4% (range 95.2-109.5%) (P ≪ 0.05). Patients treated lying down with 2 Gy single fraction received the highest relative mean lung dose on average, with 108.4% (2.2 Gy) ±2.6% of prescription (range 103.2-114.4%). Lung doses have been reported for 142 TBI patients using the lying and standing techniques described herein. Lung shielding blocks significantly reduced mean lung doses despite the addition of electron boost fields to the chest wall.

Evaluating Concordance between International Myeloma Working Group (IMWG) and Simplified Frailty Index (SFI) Among Older Adults with Multiple Myeloma (MM)

Introduction: Despite significant advances in therapeutics, older adults with MM are at increased risk of treatment related toxicity and mortality. Frailty is an aging-associated state of cumulative decline in many physiological systems, resulting in diminished resistance to stressors, including cancer therapy. In 2015, the International Myeloma Working Group (IMWG) developed a geriatric assessment (GA) based frailty index (IMWG-FI) using age, comorbidities, and physical function (instrumental activities of daily living, IADL; activities of daily living, ADL) to predict risk of toxicity and mortality among older adults with MM (Palumbo, et al., Blood 2015). However, GA is not routinely incorporated in clinical practice and a simplified frailty index (SFI; Facon et al Leukemia 2020) has been proposed as an alternative to using ECOG performance status (ECOG PS) as a proxy for physical function (IADL/ADL). However, the concordance between IMWG-FI and SFI remains relatively unknown, as well as their predictive ability in clinical practice, particularly among patients with relapsed, refractory multiple myeloma (RR-MM). Our goal was to describe the prevalence of frailty using IMWG-FI and SFI as well as evaluate their concordance among patients with newly-diagnosed (ND) and RR-MM. Methods: The Cancer and Aging Resilience Evaluation in Hematologic Malignancies (CARE-Heme) Registry is an ongoing prospective registry enrolling adults ≥50 years of age with a diagnosis of a hematologic malignancy undergoing treatment at a single institution. For this analysis, we included patients ≥50yo with ND- or RR-MM initiating a new treatment regimen (ranging from first to sixth line of treatment). All of the patients included in this study underwent a comprehensive GA prior to beginning a new line of therapy or stem cell transplant. We abstracted physician reported ECOG PS and comorbidities by reviewing medical records. We calculated IMWG frailty score as well as SFI using published methods. Each patient was categorized into frail/non-frail using the IMWG frailty score (fit, intermediate-fit, frail; collapsing fit/intermediate fit into the non-frail category) and the simplified frailty score (non-frail, frail) using published cutoffs. We measured the agreement between the total frailty scores using Spearman Correlation Coefficient and the frail/non-frail categorization using the Kappa statistic. Relevant treatment outcomes including progression-free survival, overall survival, and grade 2-5 toxicities (both hematologic and non-hematologic) were recorded until disease progression, death, or 6 cycles of treatment were completed. Results: A total of 146 adults with MM (49 ND-MM, 51 pre-transplant, and 46 RR-MM) starting a new line of therapy or ASCT between 8/2020 to 1/2022 were included in this study. The median age was 62 (IQR 57-70) with 53% males and 36% blacks. Most patients had IgG isotype (64%) with International Staging System (ISS) stage III disease (38%) whereas 30% patients had high risk cytogenetics. The distribution by IWMG Frailty category was as follows: 43% fit, 32% intermediate-fit, and 25% frail. Using SFI, 32% of patients were characterized as frail and 68% were characterized as non-frail (Figure 1). Although, the frailty scores were well correlated with each other (Spearman rho 0.67, p value <.001), the agreement between SFI and IMWG-FI in terms of frailty categorization was moderate (Kappa statistic 0.50); 79% of patients were classified in the same frailty group, however about 21% of patients were characterized in different frailty categories using the two scales (Table 1). SFI over-estimated frailty in about 14% of patients. There was very little agreement between a patient-reported vs physician rated ECOG-PS (Kappa statistic 0.13). The discordance between the two FI worsened if a patient reported version of ECOG PS (Kappa statistic 0.30) was used. Conclusions: Among older adults with MM, the prevalence of frailty ranged 25% by IMWG-FI to 32% by SFI. There was only a modest agreement between SFI and IMWG FI, which was worse when using patient reported version of ECOG PS. Studies comparing outcomes across the two frailty indices should take into account the potential for misclassification bias. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Impaired Overall Survival in Young Patients With Acute Myeloid Leukemia and Variants in Genes Predisposing for Myeloid Malignancies.

Impaired Overall Survival in Young Patients With Acute Myeloid Leukemia and Variants in Genes Predisposing for Myeloid Malignancies.

Nutritional Status at Diagnosis as Predictor of Survival from Childhood Cancer: A Review of the Literature.

Few studies so far have examined the impact of nutritional status on the survival of children with cancer, with the majority of them focusing on hematological malignancies. We summarized published evidence reporting the association of nutritional status at diagnosis with overall survival (OS), event-free survival (EFS), relapse, and treatment-related toxicity (TRT) in children with cancer. Published studies on children with leukemia, lymphoma, and other solid tumors have shown that both under-nourished and over-nourished children at cancer diagnosis had worse OS and EFS. Particularly, the risk of death and relapse increased by 30–50% among children with leukemia with increased body mass index at diagnosis. Likewise, the risk of TRT was higher among malnourished children with osteosarcoma and Ewing sarcoma. Nutritional status seems to play a crucial role in clinical outcomes of children with cancer, thus providing a significant modifiable prognostic tool in childhood cancer management. Future studies with adequate power and longitudinal design are needed to further evaluate the association of nutritional status with childhood cancer outcomes using a more standardized definition to measure nutritional status in this population. The use of new technologies is expected to shed further light on this understudied area and give room to person-targeted intervention strategies.

Precision medicine for risk prediction of oral complications of cancer therapy-The example of oral mucositis in patients receiving radiation therapy for cancers of the head and neck.

Oral complications of cancer therapy are common, markedly symptomatic, negatively impact patients' quality of life, and add significantly to the cost of care. Patients' risk of treatment-related toxicities is not uniform; most patients suffer at least one side effect, while others tolerate treatment without any. Understanding those factors which impact risk provides opportunities to customize cancer treatment plans to optimize tumor kill and minimize regimen-related toxicities. Oral mucositis (OM) is an iconic example of a clinically significant and common complication of head and neck radiotherapy. Individuals' OM risk is governed by the cumulative impact of factors related to treatment, the tumor, and the patient. In addition to OM risk prediction, a second opportunity to apply precision medicine will evolve as viable treatment options become available. Patients vary widely in how well or poorly they respond to specific treatments. What works well in one individual, might fail in another. Prospective determination of the likelihood of a patient's response or non-response is based on a range of biological interactions. Coupled with risk determination, the application of precision medicine will allow caregivers, patients, and payers to integrate risk/benefit to optimize the probability that the best treatment is be given to the most appropriate patients.

MO13-2 Predicting the treatment related toxicity by Geriatric-8 geriatric assessment screening tool

By 2022, about one-fifth of Thai population will be age 65 or older. The aging population continues to grow at an unprecedented rate, which also a main of newly diagnosed cancer patient. Cancer therapy in older adult causing higher risk for treatment related toxicity. Geriatric8 (G8) screening tool are practical and easy assessed. Moreover, it can address the impairments and have the potential to predict risk of adverse event of cancer treatment. The purpose of the study is to evaluate the relationship between cancer treatment-related toxicity and G8 score.

Using CT-based body composition metrics and frailty index in predicting survival among older adults with cancer.

12057 Background: Older adults with cancer are at an increased risk of treatment related toxicities and excess mortality during cancer treatment. While altered body composition and frailty are associated with worse survival among older adults with cancer, no prior study has examined their combined influence on survival prediction. Methods: Prospective study of older adults (≥60 years) undergoing geriatric assessment (GA) at initial visit with a medical oncologist at UAB from 9/2017-07/2021 with available abdominal computed tomography (CT) within 60 days of GA. Using multi-slice CT images from T12 to L5 level, volumetric skeletal muscle (SMV), visceral (VATV) and subcutaneous (SATV) adipose tissues, and skeletal muscle density (SMD), were derived. Sex-specific z-scores for each measure were determined. A 44-item frailty index was obtained, using the deficit accumulation model. Overall survival (OS) was defined as time from GA to death or last follow-up (11/8/2021). Kaplan-Meier estimates of survival rates were compared using log-rank statistics. Multivariable cox regression models were used to predict OS in a random sub-sample (1:1 split of training:validation set), sequentially adding frailty and each body composition measure and assessing improvement with likelihood ratio tests and Harrel’s C statistic. Results: 815 patients were included (median age 68 years, 61% men, and 75% non-Hispanic Whites. 73% had gastrointestinal malignancies (stage III, 25%, stage, IV 48%). 32% were frail, 31% pre-frail. There was a weak negative correlation between height-adjusted SMV and frailty (r = -0.16), particularly among men (r -0.24). Over a median follow-up of 25.7 months (range 0.3-49.6 months), 268 patients (33%) died. The 2-year survival rate was 75.9%, 68.5% and 52.2% among robust, pre-frail and frail (log-rank p &lt;.001), respectively. In multivariable models adjusted for age, sex, race, cancer type and cancer stage, being frail (vs robust) (Hazards Ratio, HR = 2.32; 95%CI: 1.69-3.2; p &lt;.001) and higher skeletal muscle volume (HR = 0.85; 95%CI: 0.72-0.99; p= 0.04, per SD increment) were independently associated with OS. Adding body composition and frailty to clinical variables led to significant improvement in prediction (Harrel’s C increased from 0.69 to 0.74). In the validation set, discrimination was similar (Harrel’s C = 0.72) and plots suggested good model calibration. Conclusions: CT-based body composition metrics and frailty are independent predictors of OS among older adults with cancer and improve survival prediction compared to routine clinical risk factors.

Abstract OT1-06-01: A randomised trial comparing continuation or de-escalation of bone modifying agents (BMA) in patients treated for over 2 years for bone metastases from either breast or castration-resistant prostate cancer (REaCT-HOLD BMA)

Abstract Background: Current guidelines recommend bone modifying agents (BMAs), such as bisphosphonates and denosumab, every 4 to 12 weeks to reduce the incidence of and delay the onset of symptomatic skeletal events (SSEs) in patients with bone metastases from breast cancer and castration-resistant prostate cancer (CRPC). Given the absence of level one evidence, the optimal frequency and duration of BMAs after 2 years of treatment is unknown. This is an important clinical question as the risk of SSEs decreases with time, while the risk of treatment-related toxicities increases. Methods: Patients with bone metastases from breast cancer or CRPC who have received ≥ two years of BMA treatment will be approached for this pragmatic, multicenter, open-label RCT. Using the Rethinking Clinical Trials (REaCT) methodology that incorporates the integrated oral consent model, eligible and consented patients will be randomized to either continue standard schedule BMA (every 4 or 12 weeks) or de-escalated BMA (every 24 weeks). This is a non-inferiority study. The co-primary endpoints are the physical functioning subscale of EORTC-QLQ-C30 and functional interference subscale of EORTC-QLQ-BM22. Secondary endpoints include number of patients with ≥ 1 SSE, time to development of SSE, SSE-free survival, skeletal morbidity rate, EORTC-QLQ-C30 and BM22 scores, BMA-related toxicity, and treatment adherence. To achieve 80% power for both co-primary endpoints and assuming a 10% non-compliance and 20% death rate, the planned sample size is 240 patients (120 per arm). Randomization (1:1 ratio) will be stratified by cancer type (breast vs prostate) and treatment schedule prior to randomization (Q4weeks vs. Q12weeks). A subgroup analysis comparing patients with 2-3 years vs. &amp;gt; 3 years of prior BMA treatment will be conducted. Results: The study has been open for enrollment since Oct 2020. As of July 5, 2021, the study has opened at 2 sites, 48 patients have been randomized and 8 are in screening. The study needs 60 patients randomized by September 2021 to continue to receive funding. There is a plan to open the study at two other academic centers in Ontario, Canada. Conclusion: This will be the first RCT providing level one evidence regarding the optimal frequency of BMA treatment that accounts for health-related quality of life after ≥ two years of prior BMA in this patient population. Citation Format: Terry L. Ng, Gregory R. Pond, Marta Sienkiewicz, Kednapa Thavorn, Mark Clemons. A randomised trial comparing continuation or de-escalation of bone modifying agents (BMA) in patients treated for over 2 years for bone metastases from either breast or castration-resistant prostate cancer (REaCT-HOLD BMA) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-06-01.

Dosimetric Comparisons between Proton Beam Therapy and Modern Photon Radiation Techniques for Stage I Non-Small Cell Lung Cancer According to Tumor Location.

Simple SummaryStereotactic ablative radiotherapy (SABR) is a well-established technique used to treat stage I non-small cell lung cancer (NSCLC). Proton beam therapy (PBT) offers dosimetric advantages over photon SABR techniques by reducing doses to normal organs. Hence, it is believed that PBT is helpful for patients with tumors located centrally in stage I NSCLC. However, the benefits of PBT for other locations, such as peripherally located tumors, have not been well-described. We investigated dosimetric benefits for PBT over modern photon radiation techniques for stage I NSCLC according to tumor locations. A total of 42 patients’ (including tumors that were central (11), peripheral (nine), and close to the chest wall (22)) PBT plans were compared with those of modern photon radiation techniques. In all locations, PBT significantly reduced radiation exposure to the lung and heart. To reduce potential lung and heart toxicities, PBT is ideal, even in the peripherally located stage I NSCLC.Herein, we investigated the dosimetric benefits for proton beam therapy (PBT) over modern photon radiation techniques according to tumor location (central, peripheral, and close to the chest wall) for stage I non-small cell lung cancer (NSCLC) patients. A total of 42 patients with stage I NSCLC were treated with PBT with a total dose of 50–70 Gy in four or 10 fractions considering the risk of treatment-related toxicities. Simulation plans for three-dimensional conformal radiation therapy (3D-CRT), static-field intensity-modulated radiotherapy (IMRT), and volumetric-modulated arc therapy (VMAT) were retrospectively generated using the same treatment volumes as implemented in the PBT plans for these patients. Dosimetric improvements were observed with PBT as compared with all the photon-based radiation techniques with regards to the mean lung dose, lung V5 and V10, mean heart dose, and heart V5 and V10 in all locations. Moreover, lower radiation exposure to the chest wall was observed within PBT for peripherally located and close to the chest wall tumors. All radiotherapy modalities achieved clinically satisfactory treatment plans in the current study. Notably, the usage of PBT resulted in significant dosimetric improvements in the lung and heart over photon-based techniques at all tumor locations, including the periphery, for stage I NSCLC.

Managing Multiple Myeloma in Older Adults Using Real World Evidence and Clinical Integration of a Geriatric Assessment Tool in Clinical Practice

Background: Over two thirds of patients with Multiple Myeloma (MM) are ≥ 65 years old at the time of diagnosis. Older adults are at greater risk for treatment related toxicity and inferior survival; such risks are inadequately explained by chronologic age and performance status. In 2015, the International Myeloma Working Group (IMWG) proposed a geriatric assessment (GA) based frailty index to identify older adults with MM at greatest risk of toxicities. Yet, routine implementation of GA in busy oncology practice remains challenging. We have previously shown the feasibility of a tablet-based modified Geriatric Assessment (mGA), capturing the Charlson Comorbidity Index (CCI), Katz Activity of Daily Living (ADL) Score, and Lawton Instrumental Activity of Daily Living (IADL) score, and its impact on clinical decision-making and treatment outcomes (Nathwani, et al. JOP. 2020). In the prior study, physicians recommended integration of the mGA into the electronic medical record (EMR) to improve usefulness at the clinic.Methods: We conducted a single institution pilot study to test the feasibility of integrating an electronic care planning system within the EMR such that with a single sign on, the dashboard showing results of the mGA was visualized within the EMR. Eligible patients had symptomatic MM, > 60 years old, and seeing their oncology providers to make a decision about treatment. After completing informed consent, patients completed a tablet-based mGA in clinic just prior to seeing the physician. Survey results were compiled and were immediately available for evaluation on a dashboard within the EMR. Providers reviewed the mGA results before meeting with the patient and completed a short survey after the visit regarding their own subjective impression of frailty and how the mGA influenced their treatment decision making. Agreement between provider's subjective vs mGA based frailty categorization was measured using Cohen's Kappa statistic. We measured relevant toxicity outcomes at 3 months post treatment initiation.Results: 25 patients were enrolled, with a median age of 68 (range=61-82), 52% (n=13) female, and 68% (n= 17) white. One patient did not complete the mGA survey and was not included in the analysis. The remaining patients completed the mGA successfully without interrupting clinic flow and mGA was immediately available for providers to review during the clinic visit. The average time providers spent reviewing results was of 5 (range 1-10) minutes. Providers subjectively categorized patients as 42% (n=10) fit, 58% (n=14) intermediate fit, and 0% (n=0) frail. According to the mGA, patients were 50% (n=12) fit, 29% (n=7) intermediate fit, and 21% (n=5) frail. There was an overall 46% (n=11) concordance between physician and mGA result. The most agreement was in fit status (58%, n=7) and least was frail (0%, n=0). There was 33% (n=4) agreement on intermediate fit status. The unweighted Cohen's kappa statistic was 0.09 indicating only slight agreement between the two methods. Providers reported mGA influenced their treatment decision in 33% (n=8), with the decision being either chemotherapy modification (n=6) or reduced dose transplant (n=2). One patient, who was frail and received induction treatment, died during the 3-month study period. The remaining patients (n=23) received treatment as planned.Discussion: In this study, we report the feasibility of an EMR integrated mGA tool completed by the patient prior to meeting with the physician. Patients completed the survey with assistance and without disrupting the clinic workflow. The mGA results were reviewed by providers in real time and influenced treatment decisions one third of the time. Nearly all patients (96%, n=24) completed therapy as planned. Providers tended to view the patients as more fit than the mGA result, suggesting that the mGA uncovers additional information related to the patient's ability to tolerate therapy. Toxicity follow up is ongoing and will be updated at the time of presentation. DisclosuresGiri: CareVive: Honoraria, Research Funding; PackHealth: Research Funding. Costa: BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Karyopharm: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Speakers Bureau.

The Potential for Midtreatment Albumin-Bilirubin (ALBI) Score to Individualize Liver Stereotactic Body Radiation Therapy.

Our individualized functional response adaptive approach to liver stereotactic body radiation therapy (SBRT) with assessment of indocyanine green (ICG) retention at baseline and midtreatment to detect subclinical changes in liver function, permitting dose adjustment, has decreased toxicity while preserving efficacy. We hypothesized that assessment of the albumin-bilirubin (ALBI) score at baseline and midtreatment would allow for more practical identification of patients at risk for treatment-related toxicity (TRT). Patients with hepatocellular carcinoma were treated on 3 prospective institutional review board-approved trials using baseline and midtreatment ICG to deliver individualized functional response adaptive liver SBRT. Patients received 3 or 5 fractions, with fraction 3 followed by a 1-month treatment break. TRT was a ≥2-point rise in Child-Pugh score within 6 months of SBRT. Logistic regression was used to estimate odds ratios (ORs) and confidence intervals (CIs) for assessment of TRT. Area under the receiver operating curve was used to compare predictive ability across models. In total, 151 patients underwent 166 treatments. Baseline Child-Pugh class and ALBI grade were A (66.9%), B (31.3%), or C (1.8%) and 1 (25.9%), 2 (65.7%), or 3 (8.4%), respectively. Thirty-five patients (20.3%) experienced TRT. On univariate analysis, baseline ALBI (OR, 1.8; 95% CI, 1.24-2.62; P=.02), baseline ICG (OR, 1.66; 95% CI, 1.17-2.35; P=.04), and change in ALBI (OR, 3.07; 95% CI, 1.29-7.32; P=.003) were associated with increased odds of TRT. ALBI-centric models performed similarly to ICG-centric models on multivariate analyses predicting toxicity (area under the receiver operating curve of 0.79 for both). In a model incorporating baseline and midtreatment change in ALBI and ICG, both ALBI values were statistically significantly associated with toxicity, whereas ICG values were not. Incorporation of midtreatment change in ALBI in addition to baseline ALBI improves the ability to predict TRT in patients with hepatocellular carcinoma receiving SBRT. Our findings suggest that functional response adaptive treatment could be implemented in a practical manner because the ALBI score is easily obtained from standard laboratory values.

Tobacco use, knowledge of harms, and cessation support among patients with non-tobacco related cancers.

e24029 Background: Continued cigarette smoking among patients with cancer leads to numerous adverse health outcomes, even among patients with non-tobacco-related cancers such as breast, colon, and prostate cancer. Continued smoking is associated with poorer response to cancer treatment, increased risk for treatment-related toxicities, and shorter overall survival. While some patients with a smoking-related cancer make efforts to quit smoking at the time of diagnosis, patients with other forms of cancer might not understand the negative effects of continued smoking. In this study, we assessed patient knowledge of the harms of continued smoking, previous cessation attempts, and cessation support. Methods: We surveyed 102 adults with breast, colon, and prostate cancer at three locations: an NCI-designated cancer center, an urban safety-net medical center, and a rural cancer center. Patients were asked about current smoking behaviors, beliefs about the harms of continued smoking, quit attempts and resources used, and cessation support. We also surveyed seven oncologists to assess beliefs about harms of continued smoking, cessation support provided to patients, training and confidence in cessation counseling, and barriers to providing cessation support. Results: Most patients (82%) agreed or strongly agreed that continued smoking may shorten life expectancy, and 70% agreed or strongly agreed that continued smoking increased the risk of getting a different type of cancer. Only 41% of patients agreed or strongly agreed that continued smoking may cause more side effects from cancer treatment, and only 40% agreed or strongly agreed that ongoing smoking may affect treatment response. The majority of patients (86%) had tried to quit smoking for good, with an average 4.1 quit attempts per patient. Patients reported that physicians advised them to quit the majority of the time (92%), prescribed medication 33% of the time, and followed up on cessation attempts 43% of the time. Overall, oncologists had higher knowledge of the harms of continued smoking on treatment outcomes and survival. Those in practice for 20 years or more had higher confidence in cessation counseling than those in practice less than 4 years. Oncologists described lack of time and lack of confidence in cessation counseling as barriers to providing more cessation support. Conclusions: Among 102 patients with breast, colon, and prostate cancer who currently smoke, there was incomplete knowledge of the harms of continued smoking. Oncologists believe that tobacco cessation is important and frequently advise patients to quit, however they less frequently prescribe medication or follow up on cessation efforts. Interventions are needed to educate patients with cancer about the harms of continued smoking and to provide further cessation support.

Current Status of Biologics in Perioperative Treatment for Resectable or Borderline Resectable Liver Metastases

This review provides an overview of the current role of biologics, anti-vascular endothelial growth factor (VEGF) inhibitors and anti-epidermal growth factor receptor (EGFR) inhibitors, in the perioperative treatment of colorectal liver metastases as well as a discussion of their future trends. Over the past decade, a number of clinical trials have suggested that the use of biologics with cytotoxic agents may increase median overall survival in certain subsets of patients with colorectal liver metastases. The benefit of these agents is limited to borderline resectable and unresectable hepatic metastases and is not seen in upfront resectable disease. In the RAS wild-type population, the difference in efficacy of VEGF and EGFR inhibitors in combination with chemotherapy is minimal. These agents perform differently depending on primary tumor location; bevacizumab has greater efficacy in right-sided tumors, whereas cetuximab has greater efficacy in left-sided tumors. While biologics benefit patients in the neoadjuvant setting, studies have not shown similar results in the adjuvant setting. Given the variability of patient presentations as well as the risk of treatment-related toxicity, the addition of biologics requires careful consideration of patient’s medical fitness, surgical risk, and tumor profile.

High Dose Flamsa, CLAG or FLAG-Based Sequential Conditioning Regimen Followed By Allogeneic Hematopoietic Transplantation Results in Favorable Outcome for High Risk Acute Myeloid Leukemia, Myelodysplastic Syndrome, Myeloproliferative Neoplasia Patients : A Multicenter Study in Singapore

Introduction: Allogeneic hematopoietic cell transplant (allo-HCT) is an effective consolidative treatment for patients with certain hematological malignancies and gives the best outcome when done in remission. However, patients with refractory acute myeloid leukemia (AML), certain forms of myeloproliferative neoplasia (MPN), and myelodysplastic syndrome (MDS) deemed unable to achieve remission with standard induction are often excluded from allo-HCT with conventional conditioning regimen as pre-transplant remission could not be achieved. Recently, a sequential transplant approach, as developed by the Munich group, comprising of intensive cytoreductive chemotherapy FLAMSA (fludarabine/amsacrine/cytarabine) to decrease leukemia cell burden shortly prior to conditioning regimen, had been successfully used for high-risk (HR) AML/MDS with promising results. Methods: We studied 56 patients (median age, 52 years; range 17-68) with HR AML (n=45), as defined by refractory, relapsed disease, secondary leukemia, complete remission with adverse-risk cytogenetics according to ELN criteria, or high/very high risk refined Disease Risk Index (DRI), MPN (n=2), and HR MDS (n=9) according to IPSS-R, undergoing allo-HCT using the sequential transplant approach in 2 transplant centers in Singapore between January 2009 and June 2020. The sequential transplant approach combined a cytoreductive chemotherapy, which consisted of either FLAMSA (n=17), FLAG +/- Ida [fludarabine/cytarabine/granulocyte colony stimulating factor (GCSF) +/- idarubicin] (n=23), or CLAG (clofarabine +/- cytarabine +/- GCSF) (n=15), followed by reduced intensity (RIC) (N=48) or myeloablative (MAC) (N=8) conditioning regimen. All patients received peripheral blood stem cell from matched related donors (N=30), mismatched related donors (N=3), matched unrelated donors (N=16), or mismatched unrelated donors (N=7). Post-grafting immunosuppression consisted of calcineurin inhibitor and mycophenolate mofetil in all patients. Thymoglobuline or post-transplant cyclophosphamide were added for GVHD prophylaxis in unrelated donor transplant and mismatched related donors, respectively. Results: The median time to neutrophil &amp;gt; 1000/μL was 11 days (range, 8-19). With a median follow-up of 44 months (range, 1-123), the Kaplan-Meier estimate of overall (OS) and leukemia-free (LFS) survivals at 5 years were 49% (95% CI, 35-62) and 37% (95% CI, 23-52), respectively. The 2-years cumulative incidence of relapse and non-relapse mortality (NRM) were 47% (95% CI, 32-60) and 13% (95% CI, 6-24), respectively. Patients receiving FLAG or CLAG-based sequential regimen showed lower cumulative incidence of NRM (2-year cumulative incidence for NRM: 5% vs 29%; p=0.018), and similar relapse (2-year cumulative incidence for relapse: 49% vs 53%; p=0.64), as compared to patients given FLAMSA-based sequential regimen, resulting in a trend towards more favourable OS (5-year OS: 53% vs 41%; p=0.29) and LFS (5-year LFS: 46% vs 20%; p=0.08). In multivariable analysis, only refined DRI showed significant impact on OS (p=0.04), but has no significant impact on LFS, NRM, and relapse. The 5-year OS for patients with intermediate/high risk and very high risk DRI were 59% and 27%, respectively (p=0.017), and the corresponding 5-year LFS were 46%, and 20% (p=0.06), respectively (Figure 1 &amp; Figure 2). The intensity of conditioning regimen did not significantly impact on OS, LFS, relapse, and NRM. Conclusions: Sequential transplant conditioning with FLAMSA, FLAG or CLAG followed by allo-HCT is an effective strategy in overcoming the dismal prognosis of HR AML, MDS and MPN, and enabling favourable long-term disease-free survival. More studies on effective strategies such as post-transplant maintenance therapy with prophylactic donor lymphocyte infusion, are needed to further eliminate the risk of relapse, without increasing risk of treatment related toxicity. Disclosures No relevant conflicts of interest to declare.

Three Drug Combinations in the Treatment of Fit Elderly Multiple Myeloma Patients.

The multiple myeloma (MM) non transplant eligible (NTE) population is growing in line with the aging of the population in Western countries. Historically, this population has been known for having a greater risk of treatment related toxicity, and therefore drug development was slow and rather oriented towards the improvement of safety profile than the optimization of disease control. However, NTE MM patients, at least for the fit/non frail patients in recent years, seemed to have benefited more from a less palliative care to improve the depth of response and then prolong survival. NTE MM being a quite heterogeneous population, there are still a number of groups of patients that are in need of more efficient therapy, avoiding unnecessary toxicity, particularly for the frail patients. The use of triplet regimen with a melphalan-prednisone (MP) backbone has long been the standard of care for NTE MM, often dedicated to non-frail patients. New standards of care, triplet, and even quadruplet combinations, are emerging on the basis of the MP backbone but also on the more recently approved lenalidomide-dexamethasone (Rd) backbone. These developments were largely possible in line with the development of antibody-based immunotherapies (IT) in MM. The objective to improve outcomes with an acceptable safety profile will see other key therapeutic developments such as the dropping of dexamethasone early in the disease course or various attempts to allow permanent treatment discontinuation with a prolonged disease control. In that context, it is possible that immunomonitoring, minimal residual disease (MRD), and genomic risk-adaptation will become key elements of the treatment decisions on triplet-based regimens.

Cabotegravir and rilpivirine for the treatment of HIV

ABSTRACTIntroduction: Antiretroviral treatment (ART) has led to improved control of HIV infection, giving the opportunity of exploring therapeutic alternatives as new long-acting (LA) regimens, that might improve the quality of life of people living with HIV (PLWH).Areas covered: This article overviews the pharmacokinetic and pharmacodynamic properties of LA cabotegravir and rilpivirine (CR), two nanoformulated drugs of intramuscular administration and focuses on assessing its role on the treatment of HIV infection.Expert opinion: In addition to the advantage of treatment simplification, which could be especially beneficial for population subgroups with significant HIV-related stigma, it also reduces the number of drugs, and probably, the risk of treatment-related toxicity. The similar efficacy when compared to oral triple therapies in clinical trials and the high satisfaction rates among both professionals and patients make LA CR a suitable alternative for the control of HIV infection in the modern era.