Patient-reported Quality Of Life Outcomes Research Articles

Quality of Life and Depression Symptoms After Therapy De-Escalation in HPV+ Oropharyngeal Squamous Cell Carcinoma

Despite interest in therapy de-escalation for survivors of human papillomavirus-mediated oropharyngeal squamous cell carcinoma (HPV-positive OPSCC), the association of de-escalated therapy with patient-reported quality of life (QoL) outcomes and burden of depressive symptoms remains unclear. To identify associations between clinicopathologic and therapeutic variables with patient-reported QoL outcomes and depression symptom burden in patients with HPV-positive OPSCC, who were enrolled in a therapy de-escalation trial. In this nonrandomized controlled, open-label, curative-intent therapy de-escalation clinical trial in adults with stage I, II, and III HPV-positive OPSCC, patients were recruited from a high-volume head and neck oncology practice. The main outcomes of this study included quantitative, patient-reported QoL and depression symptoms per well-validated inventories. Patient-reported QoL was based on Functional Assessment of Cancer Therapy-Head & Neck (FACT-HN) scores (range, 0-148; lower score indicates inferior QoL). Patient-reported depression-related symptom burden was based on Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) scores (range, 0-27; a higher score indicates a higher burden of depression symptoms). Baseline clinicopathologic and treatment variables were paired with FACT-HN and QIDS-SR scores at baseline, 3, 6, 12, 24, and 36 months. Linear mixed-effect models with a random intercept were used for each participant and fixed effects for other measures. Regression coefficients are reported with 95% CIs. A total of 95 patients were followed up for a median (IQR) of 2.2 (1.6-3.2) years. Of these, 93 patients (98%) were male with a mean (SD) age of 60.5 (8.2) years. Overall, 54 participants (57%) had a history of current or former smoking, 47 (50%) underwent curative-intent surgery (with or without adjuvant therapy), and 48 (50%) underwent primary radiotherapy (with or without chemotherapy). The median (IQR) radiotherapy dose was 60 (60-70) Gy. Five deaths and 2 recurrence events were observed (mean [SD] recurrence interval, 1.4 [1.5] years). A higher radiotherapy dose was the only modifiable factor associated with inferior patient-reported QoL (lower FACT-HN) (coefficient, -0.66 [95% CI, -1.09 to -0.23]) and greater burden of depression-related symptoms (higher QIDS-SR) (coefficient, 0.11 [95% CI, 0.04-0.19]). With the 70-Gy dose as reference, improvements in FACT-HN and QIDS-SR scores were identified when patients received 51 to 60 Gy (coefficient, 12.75 [95% CI, 4.58-20.92] and -2.17 [-3.49 to -0.85], respectively) and 50 Gy or lower (coefficient, 15.03 [4.36-25.69] and -2.80 [-4.55 to -1.04]). In this nonrandomized controlled, open-label, curative-intent therapy de-escalation trial, a higher radiotherapy dose was associated with inferior patient-reported QoL and a greater burden of depression-related symptoms. This suggests opportunities for improved QoL outcomes and reduced depression symptom burden with a reduction in radiotherapy dose. ClinicalTrials.gov Identifier: NCT04638465.

Long-term quality of life outcomes in patients undergoing microsurgical resection of vestibular schwannoma

BackgroundWhile previous studies have assessed patient reported quality of life (QOL) of various vestibular schwannoma (VS) treatment modalities, few studies have assessed QOL as related to the amount of residual tumor and need for retreatment in a large series of patients. Objective: To assess patient reported QOL outcomes following VS resection with a focus on extent of resection and retreatment. MethodsA retrospective chart review was performed using single-center institutional data of adult patients who underwent VS resection by the senior authors between 1989-2018 at Loyola University Medical Center. The Penn Acoustic Neuroma Quality of Life (PANQOL) survey was sent to all patients via postal mail. ResultsFifty-five percent of 367 total patients were female with a mean age of 61.6 years (SD 12.63). The mean period between surgery and PANQOL response was 11.4 years (IQR: 4.74-7.37). The median tumor size was 2 cm (IQR: 1.5-2.8). The mean total PANQOL score was 70 (SD 19). Patients who required retreatment reported lower overall scores (μdiff = -10.11, 95% CI: -19.48 to -0.74; p = 0.03) and face domain scores (μdiff = -20.34, 95% CI: -29.78 to -10.91; p < .001). There was no association between extent of resection and PANQOL scores in any domain. ConclusionIn an analysis of 367 patients who underwent microsurgical resection of VS, extent of resection did not affect PANQOL scores in contrast to previous reports in the literature, while the need for retreatment and facial function had a significant impact on patient-reported outcomes.

Mature results of a phase 2 pilot study of radium-223 and radiotherapy in untreated hormone-naïve men with oligometastatic prostate cancer to bone.

160 Background: We hypothesized that treatment with Radium-223 (Ra223) and to ≤5 sites of bony metastases could safely delay the time to start androgen deprivation therapy (ADT) and maintain quality of life (QoL). Methods: 20 men previously treated with surgery, radiation, or both for M0 PCa later developed ≤5 bone-only mets were eligible for this prospective trial. Inclusion: testosterone ≥ 100 ng/dL and mets on conventional bone scan, validated by a CT, MRI, or PET/CT. Exclusion: LHRH therapies after initial treatment or N1 disease at diagnosis of bone mets. Therapy was 6 cycles of Ra223 and SBRT (30 Gy in 5 fractions between cycles 1-2). Bone scan was performed at baseline and q3 months. PSA was evaluated monthly during the Ra223 course and q3 months after. Therapeutic effectiveness was defined as ≥20% of patients meeting the primary endpoint of freedom from ADT (FFAdt) use at 15 months. Discontinuation of study therapy occurred if: PSA rise &gt; 10% if baseline PSA &gt;20ng/ml, PSA&gt;20 if baseline PSA &lt;20 ng/ml, radiographic progression or a skeletal-related event (SRE). All endpoints were timed from the Cycle 1 radium date. Patients were followed for 2 years. Clinically significant changes in patient-reported outcome (PRO) measures were defined as &gt;1/2 standard deviation from the mean baseline value and were censored after the time of ADT use. Continuous and categorical covariates were compared using the Wilcoxon rank sum and Pearson’s Chi2 tests and univariate Cox regression. Statistical significance was considered at P&lt;0.05. Results: The median number of Ra223 cycles was 6. 6 patients had &lt;6 cycles (range 2-5) due to progression. FFAdt at 15 and 24 months was 50.0% and 40.0%, respectively (p&lt;0.001). Median time to ADT was 15 months. 11 (55%) and 5 (25%) patients had a PSA decline exceeding 50% and 90%, respectively. Two patients had undetectable (PSA&lt;0.01) at 2 years. There were no significant changes from baseline in any PRO QoL domain (physical functioning, anxiety, depression, fatigue, satisfaction with participation in social roles, sleep disturbance, and pain interference). There were 2 patients with Grade 3 SREs (bone fracture, pain). Grade 2+ events attributed as possible or likely to Ra-223 were seen in 4 patients (bone pain, fatigue, fracture, decreased WBC count, and other). Grade 2+ events attributed as possible or likely to EBRT were seen in 2 patients, including fatigue and other pain. No differences were noted for age, baseline PSA, days from primary treatment, NCCN risk group, TNM stage, ISUP grade group, BMI, or # of lesions in those who met or failed the primary endpoint (all p&gt;0.05). Conclusions: In this prospective pilot study, the first-line use of Ra223 and SBRT to conventionally imaged oligomets in hormone-naïve men resulted in a significant delay in ADT use compared to historical control. The therapy is well tolerated, maintains QoL, and may result in undetectable PSA. Clinical trial information: NCT03304418 .

Population-based patient-reported quality of life outcomes following low-dose-rate versus high-dose-rate brachytherapy monotherapy for low-intermediate risk prostate cancer.

To evaluate patient reported quality of life outcomes (QoL) following low-dose-rate brachytherapy (LDR-BT) and high-dose-rate brachytherapy (HDR-BT) monotherapy for prostate cancer at a population-based setting. The study comprised men with low-intermediate risk prostate cancer in the Prostate Cancer Outcomes Registry Victoria (PCOR-Vic), who were treated with LDR-BT or HDR-BT monotherapy between 2015 and 2020 and completed the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire 12-month post-treatment. Men who had ADT were excluded (n = 12). Differences in substantial symptoms (i.e. 'moderate' or 'big' problem on a 5-point Likert scale) between LDR-BT and HDR-BT arms were evaluated using Pearson's chi-squared test. Multivariable linear regressions were used to estimate differences in EPIC-26 urinary, bowel and sexual functional domain scores between LDR-BT and HDR-BT arms. Overall, 198 men were included in this study, of which 167 (84%) had LDR-BT and 31 (16%) had HDR-BT. 9 (4.6%), 10 (5.1%) and 56 (28%) reported substantial symptoms for overall urinary, bowel and sexual function at 12-month post-treatment, with no significant difference between LDR-BT and HDR-BT arms. The adjusted mean differences in urinary incontinence, urinary obstructive, bowel and sexual function domain scores between LDR-BT and HDT-BT were: -3.53 (-8.21 to 1.14), -1.27 (-6.88 to 4.35), -0.01 (-5.63 to 5.63) and -8.68 (-21.44 to 4.07) respectively - these were not statistically significant and did not meet the minimal clinically important difference. This is the first Australian population-based study comparing QoL in men who had LDR-BT and HDR-BT, with no statistically or clinically significant differences in QoL observed at 12-month post-treatment.

Potential Dosimetric Predictors of Patient-Reported Quality of Life for Head and Neck Cancer Following Chemoradiation IMRT

This study aims to identify both acute and late patient patient-reported salivary quality of life outcomes in patients with head and neck cancer treated with chemoradiation therapy on a prospective trial. A cohort of 40 patients with head and neck cancers were included in the study. All patients underwent concurrent chemoradiation therapy using IMRT delivery (1 patient on one Linac, 24 patients on a different Linac, and 15 on a helical delivery machine). All patients were asked to complete the University of Washington Quality of Life (UOW-QOL) questionnaire at baseline, immediately after treatment, as well as at 1 month, 3 months, 6 months, 12 month and 18 months post-treatment. For the salivary quality of life (QOL) outcome scores, the possible responses were scored on a discreet scale of 100, 70, 30, and 0, with 100 as normal and 0 as dysfunctional. Dosimetric endpoints achieved based on the treatment plan, such as maximum/mean/minimum doses, V30 (percent volume receiving 30 Gy dose), and Dy (dose received to y percent volume) were collected for the bilateral salivary glands, bilateral temporomandibular joint and bilateral submandibular glands. The associations between these dosimetric parameters and the corresponding salivary QOL scores at each time point were analyzed. A Wilcoxon test was performed to identify any differences in the dosimetry and salivary QOL scores among the four different responses. At short-term follow-up including 1- and 6-month, the distribution of the mean dose received by the right parotid was significantly different between the patients that reported a salivary QOL score of 30 and those that reported 100, with p-values of 0.007 for the 1-month comparison and 0.006 for the 6-month comparison. This was also seen for the V30, with p-values of 0.027 for the 1-month comparison and 0.013 for the 6-month comparison. At 3 months, the maximum dose received by the left temporomandibular joint was significantly different between the patients that reported 30 and those that reported 70, with a p-value of 0.038. At 6 months, the average dose distribution of the right submandibular gland received between the patients that reported a score of 30 and 100 was also significantly different, with a p-value of 0.006. At the long-term follow-up time points of 12 and 18 months, no significant differences were found. The significant differences seen in the data suggest that the dosimetry may have effects on patient reported salivary QOL at short-term follow-up but not long-term. This provides a new perspective into how a patient's QOL over a period of time could be affected by the amount of dose to critical organs. These results also serve as the basis for further investigation into the actual delivered dose, which could differ from the planned dose due to daily anatomic changes over the course of head and neck radiotherapy delivery. These daily volumetric and dosimetric changes may guide early adaptive treatment to improve patient-reported QOL outcomes.

Long Term Patient Reported Quality of Life Outcomes and Patient Satisfaction of 1-Week Hypofractionated Whole Breast Radiation Therapy Using IMRT for Early-Stage Breast Cancer

Novel whole breast radiation therapy (WBRT) regimens have been recently reported with the aim of improving patient convenience while preserving local control and breast cosmesis. The UK FAST Forward trial showed that 26 Gy in 5 fx using 3D conformal WBRT was equivalent to the standard 3-week regimen. However, the use of inverse planned intensity modulated radiation therapy (IMRT) for this novel ultra-hypofractionated regimen has not been previously studied. We aim to study the patient reported quality of life (QOL) outcomes and patient satisfaction of WBRT using IMRT delivering 26 Gy in 5 fractions. Patients receiving WBRT with 26 Gy in 5 fractions using IMRT at our institution from 2020 to 2022 were included. Patients were treated with 26 Gy in 5 daily fx with or without a single fx boost of 4-5.2 Gy. IMRT plans were generated using inverse planning with 2 to 3 volumetric modulated arcs (VMAT). To assess patient-reported QOL outcomes, a questionnaire was prospectively administered at 1 month post treatment and yearly thereafter including the EORTC QLQ-BR23 breast cancer module and other patient satisfaction questions. Patient assessment involved a four-point scale (not at all, a little, quite a bit, and very much; very satisfied, moderately satisfied, moderately dissatisfied, and very dissatisfied). Here, we report the 1-year patient reported acute toxicity QOL outcomes and patient satisfaction for those undergoing IMRT based WBRT. Cross-sectional analyses were used to determine the prevalence of "quite a bit" or "very much" effects versus "not at all" or "a little" effects. A total of 96 patients were included. The median age at diagnosis was 65 years. The most common histology was invasive ductal carcinoma (53.1%). ER-positivity was found in 75.5% patients. Oncoplastic reconstruction was used in 51.0% patients. The median tumor size was 1.5 cm. There were 4/98 (4.3%) node positive patients and 22.5% received adjuvant chemotherapy. Endocrine therapy was used in 74.5% patients. A boost fraction was delivered in 95.9% patients. At the 1-year assessment, only 1/35 (2.9%), 2/35 (5.7%), and 4/35 (11.4%) patients reported "quite a bit" or "very much" breast pain, skin problems, and changes in breast appearance respectively. Additionally, 32/35 (91.4%) patients were either "very satisfied" or "moderately satisfied" with their treatment, while 32/35 (91.4%) patients reported "excellent" (n = 12) or "good" (n = 20) physical appearance of the breast. WBRT using inverse planned IMRT with 26 Gy in 5 fx shows excellent patient reported QOL and patient satisfaction at 1-year post RT. Longer follow up is needed to assess the long-term toxicity, normal tissue effects, and cosmetic outcomes of IMRT based delivery of this ultra-hypofractionated regimen.

P06.09.B TRIAL IN PROGRESS: PHASE 1 DOSE-FINDING STUDY TO EVALUATE SAFETY AND TOLERABILITY OF CVGBM IN PATIENTS WITH NEWLY DIAGNOSED AND SURGICALLY RESECTED MGMT-UNMETHYLATED GLIOBLASTOMA

Abstract BACKGROUND Glioblastoma (GBM) is characterized by a low mutational burden limiting the number of neoantigen targets for cancer vaccines. Vaccination against tumor-associated antigens over-presented via MHC class I and II in GBM is an alternative that has shown promise in previous trials. One cancer vaccine containing peptides presented by HLA-A*02-01 (class I) and some DR alleles (class II), showed evidence of peripheral vaccine-induced immune response against these peptides in patients with GBM. Our study will assess the safety and immunogenicity of the messenger ribonucleic acid (mRNA)-based multiepitope vaccine CV-GBM, an investigational therapeutic mRNA vaccine, encoding eight of these peptides that have demonstrated immunogenicity as peptide vaccines. CV-GBM consists of a mRNA with unmodified nucleotides formulated with lipid nanoparticles. MATERIAL AND METHODS CV-GBLM-001 is a first-in-human, open-label, international, dose-escalation phase 1 trial. HLA-A*02:01-positive patients with newly diagnosed MGMT-unmethylated GBM (CNS WHO Grade 4), including IDH-wildtype astrocytoma with a molecular signature of unmethylated MGMT-GBM who have had a gross total or partial resection and who completed post-surgery radiotherapy with or without chemotherapy, are eligible to receive CVGBM. The trial comprises a dose-escalation part (Part A) followed by a dose-expansion part (Part B). In Part A, the starting dose is 12 µg mRNA, which may be escalated to 25 µg, 50 µg and 100 µg, with 3 to 6 patients per dose level. Dose escalation will be guided by a Bayesian logistic regression model. Patients will receive 7 doses of CVGBM by intramuscular injection on Days 1, 8, 15, 29, 43, 57, and 71, followed by 6 optional doses at 6-week intervals, up to 1 year after the first dose or until disease progression or intolerable toxicity. An independent Data and Safety Monitoring Board will recommend the dose for expansion in Part B in which about 20 patients will be enrolled. Biomarkers and vaccine-induced innate and adaptive immunogenicity, including, but not limited to, systemically induced cytokines and chemokines and antigen-specific CD4+ and CD8+ T cells, will be monitored in the blood, and optionally in vaccine-draining lymph nodes and relapsed tumor. In addition to the primary safety objectives, secondary objectives of efficacy (progression-free survival, overall survival) and patient-reported quality of life outcomes will be assessed. Trial sponsor: CureVac SE, Germany.

PP02 Presentation Time: 9:29 AM: Long Term Rectal Patient-Reported Quality of Life Outcomes Among Patients Treated with Pd-103 LDR Prostate Brachytherapy

PP02 Presentation Time: 9:29 AM: Long Term Rectal Patient-Reported Quality of Life Outcomes Among Patients Treated with Pd-103 LDR Prostate Brachytherapy

Engagement, Retention, and Acceptability in a Digital Health Program for Atopic Dermatitis: Prospective Interventional Study.

Patients with atopic dermatitis can experience chronic eczema with pruritus, skin pain, sleep problems, anxiety, and other problems that reduce their quality of life (QoL). Current treatments aim to improve these symptoms and reduce inflammation, but poor treatment adherence and disease understanding are key concerns in the long-term management of atopic dermatitis. Digital therapeutics can help with these and support patients toward a healthier lifestyle to improve their overall QoL. The aim of the study is to test the feasibility of a digital health program tailored for atopic dermatitis through program engagement, retention, and acceptability. Adults with atopic dermatitis were recruited in Iceland for a 6-week digital health program delivered through a smartphone app. Key components of the digital program were disease and trigger education; medication reminders; patient-reported outcomes (PROs) on energy levels, stress levels, and quality of sleep (referred to as QoL PROs); atopic dermatitis symptom PROs; guided meditation; and healthy lifestyle coaching. The primary outcome was program feasibility, as assessed by in-app retention and engagement. User satisfaction was assessed by the mHealth (ie, mobile health) App Usability Questionnaire (MAUQ). A total of 21 patients were recruited (17 female, mean age 31 years), 20 (95%) completed the program. On average, users were active in the app 6.5 days per week and completed 8.2 missions per day. The education content, medication reminders, and PROs had high user engagement and retention; all users who were exposed to the QoL PROs (n=17) interacted with these, and 20/21 (95%) users were continuously engaged with the education missions, medication missions, and symptom PROs. Continued engagement with the step counter and mind missions among exposed users was lower (17/21 and 13/20 participants, respectively). Medication reminder and education task completion remained high over time (at least 18/20, 90%), but weekly interactions declined. All assigned users completed atopic dermatitis symptom PROs on weeks 1-5 and only one did not do so on week 6; the reported number and total severity of atopic dermatitis symptoms reduced during the program. Regarding the QoL PROs, 16/17 (94%) and 14/17 (82%) users interacted with these at least 3 times in the first and last week of the program, respectively, and all reported improvements over time. User satisfaction was high with a total score of 6.2/7. We found high overall engagement and retention in a targeted digital health program among patients with atopic dermatitis, as well as high compliance with missions relating to medication reminders, patient education, and PROs. Symptom number and severity were reduced, and QoL PROs improved over time. We conclude that a digital health program is feasible and may provide added benefits for patients with atopic dermatitis, including the tracking and improvement of atopic dermatitis symptoms.

Prostate Stereotactic Body Radiation Therapy With a Focal Simultaneous Integrated Boost: 5-Year Toxicity and Biochemical Recurrence Results From a Prospective Trial

Stereotactic body radiation therapy (SBRT) is increasingly used as a definitive treatment option for patients with prostate adenocarcinoma. The aim of this study was to assess the late toxicity, patient-reported quality of life outcomes, and biochemical recurrence rates after prostate SBRT with simultaneous integrated boost (SIB) targeting lesions defined by magnetic resonance imaging (MRI). Patients were eligible if they had biopsy-proven low- or intermediate-risk prostate adenocarcinoma, one or more focal lesions on MRI, and an MRI-defined total prostate volume of <120 mL. All patients received SBRT delivered to the entire prostate to a dose of 36.25 Gy in 5 fractions with an SIB to the lesions seen on MRI to 40 Gy in 5 fractions. Late toxicity was defined as any possible treatment-related adverse event occurring after 3 months from the completion of SBRT. Patient-reported quality of life was ascertained using standardized patient surveys. A total of 26 patients were enrolled. Six patients (23.1%) had low-risk disease and 20 patients had intermediate-risk disease (76.9%). Seven patients (26.9%) received androgen deprivation therapy. Median follow-up was 59.5 months. No biochemical failures were observed. Three patients (11.5%) experienced late grade 2 genitourinary (GU) toxicity requiring cystoscopy, and 7 patients (26.9%) had late grade 2 GU toxicity requiring oral medications. Three patients (11.5%) had late grade 2 gastrointestinal toxicity characterized by hematochezia requiring colonoscopy and steroids per rectum. There were no grade 3 or higher toxicity events observed. The patient-reported quality-of-life metrics at the time of last follow-up were not significantly different than the pre-treatment baseline. The results of this study support that SBRT to the entire prostate to a dose of 36.25 Gy in 5 fractions with focal SIB to 40 Gy in 5 fractions has excellent biochemical control and is not associated with undue late gastrointestinal or GU toxicity or long-term quality of life decrement. Focal dose escalation with an SIB planning approach may be an opportunity to improve biochemical control while limiting dose to nearby organs at risk.

TRIAL IN PROGRESS: ODRONEXTAMAB, A CD20×CD3 BISPECIFIC ANTIBODY, FOR THE TREATMENT OF RELAPSED/REFRACTORY MARGINAL ZONE LYMPHOMA (R/R MZL)—A COHORT FROM THE ELM‐2 STUDY

Introduction: MZL is a heterogeneous disease comprising 3 subtypes, extra-nodal MZL of mucosa-associated lymphoid tissue, nodal MZL, and splenic MZL. Treatment of R/R MZL is similar to other indolent B-cell non-Hodgkin lymphoma (B-NHL) subtypes (e.g., follicular lymphoma [FL]), comprising rituximab-based immunochemotherapy regimens that achieve an objective response rate (ORR) of ∼45%–80%. Options after progression on rituximab-based regimens include the BTK inhibitor ibrutinib, which demonstrated an ORR of 46%, but a compete response (CR) rate of only 3%, in its pivotal trial in R/R MZL. Overall, limited options are available after progression on current therapies, and a need remains for more effective treatments for R/R MZL. Odronextamab is a bispecific antibody that binds CD20-expressing B-NHL cells and CD3 on T cells. In the Phase 1 ELM-1 study, odronextamab monotherapy showed antitumor activity and a manageable safety profile in a range of R/R B-NHL subtypes, including MZL (n = 6; ORR 67%) (Bannerji et al. Lancet Haematol, 2022). In the Phase 2 ELM-2 study, odronextamab elicited an ORR of 82% and CR rate of 75% in patients with heavily pretreated R/R FL (Kim, et al. ASH, 2022). These positive data in an indolent B-NHL subtype support evaluation of odronextamab in R/R MZL. Methods: ELM-2 (NCT03888105) is an open-label study of odronextamab in patients with R/R B-NHL comprising 5 disease-specific cohorts: FL, diffuse large B-cell lymphoma, mantle cell lymphoma, MZL, and other B-NHLs. Each cohort will be evaluated separately, and patients recruited from sites across North America, Europe, and Asia-Pacific regions. The MZL cohort is planned to include 78 patients, who will receive IV odronextamab monotherapy until disease progression or other protocol-defined reason for treatment discontinuation. Odronextamab is administered according to a step-up regimen during the first 21-day cycle (C), consisting of 0.7 mg split over C1 Day (D) 1 (0.2 mg) and C1D2 (0.5 mg), 4 mg split over C1D8 and C1D9, and 20 mg split over C1D15 and C1D16. The full 80 mg dose is given QW during C2 to C4, then 160 mg Q2W from C5 onwards. If a patient achieves a CR and has a durable response for ≥9 months after initial determination of the CR, then dosing interval will be decreased from Q2W to Q4W. Patients eligible for the MZL cohort will be ≥18 years of age; relapsed/refractory to ≥2 prior lines of systemic therapy; ECOG performance status ≤1; and have adequate bone marrow and hepatic functions. Patients with prior allogeneic stem cell transplant or CAR T treatment will be excluded. Primary endpoint is ORR (Lugano classification; assessed by independent central review). Key secondary endpoints include ORR (investigator evaluation); CR rate; progression-free survival; overall survival; duration of response; safety; pharmacokinetics; and patient-reported quality of life outcomes. As of January 2023, 19 patients with MZL had enrolled. Encore Abstract—previously submitted to ASCO 2023 and EHA 2023 The research was funded by: Regeneron Pharmaceuticals, Inc. Keywords: indolent non-Hodgkin lymphoma, immunotherapy, ongoing trials Conflicts of interests pertinent to the abstract. T. M. Kim Consultant or advisory role Boryung, AstraZeneca/MedImmune, Takeda, Novartis, Janssen, Hanmi, and Regeneron Pharmaceuticals, Inc Honoraria: Takeda, Janssen, Regeneron Pharmaceuticals, Inc, Samsung Bioepis, and AstraZeneca Research funding: Celgene, Boryung, Boehringer-Ingelheim, BMS, Bayer, AstraZeneca/MedImmune, Takeda, Roche/Genentech, Novartis, Janssen, Hanmi, Genmab, Merck Serono, Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc, and Sanofi M. Taszner Consultant or advisory role Roche and Takeda Honoraria: Roche, Takeda, Novartis, and Servier Educational grants: Roche A. Chaudhry Employment or leadership position: Regeneron Pharmaceuticals, Inc Stock ownership: Regeneron Pharmaceuticals, Inc M. Ufkin Employment or leadership position: Regeneron Pharmaceuticals, Inc Stock ownership: Regeneron Pharmaceuticals, Inc A. Uppala Employment or leadership position: Regeneron Pharmaceuticals, Inc Stock ownership: Regeneron Pharmaceuticals, Inc A. Sabir Employment or leadership position: Regeneron Pharmaceuticals, Inc Stock ownership: Regeneron Pharmaceuticals, Inc H. Mohamed Employment or leadership position: Regeneron Pharmaceuticals, Inc Stock ownership: Regeneron Pharmaceuticals, Inc S. Ambati Employment or leadership position: Regeneron Pharmaceuticals, Inc Stock ownership: Regeneron Pharmaceuticals, Inc E. Bachy Consultant or advisory role Roche, Gilead, ADC Therapeutics, Takeda, Novartis, and Incyte Honoraria: Kite, Gilead, Novartis, Roche, Incyte, Miltenyi Biotech, Takeda, and Sanofi Research funding: Amgen and BMS

Towards Response ADAptive Radiotherapy for organ preservation for intermediate-risk rectal cancer (preRADAR): protocol of a phase I dose-escalation trial

IntroductionOrgan preservation is associated with superior functional outcome and quality of life (QoL) compared with total mesorectal excision (TME) for rectal cancer. Only 10% of patients are eligible for organ...

Glossectomy for the treatment of oral cavity carcinoma: Quantitative, functional and patient-reported quality of life outcomes differ by four glossectomy defects

ObjectiveThe goal was to characterize four clinically distinct glossectomy defects to establish significant quantitative cut points using functional metrics, the MD Anderson Dysphagia Index (MDADI) and speech intelligibility. MethodsPopulation included 101 patients treated with surgery, adjuvant radiation per NCCN guidelines, and ≥ 12 months follow-up. ResultsDefect groups: subtotal hemiglossectomy (1), hemiglossectomy (2), extended hemiglossectomy (3) and oral glossectomy (4) were compared: All outcomes supported a four defect model. Intergroup comparison of outcomes with subtotal hemiglossectomy as reference (p value): Tongue Protrusion <0.001,<0.001,<0.001; Elevation <0.001,<0.001,<0.001; Open Mouth Premaxillary Contact Elevation <0.001,<0.001,<0.001; Obliteration 0.6,<0.001,<0.001; Normalcy of Diet, <0.3,<0.001,<0.001; Nutritional Mode, <0.9,<0.8,<0.001; Range of Liquids, <0.4,<0.016,<0.02; Range of Solids, <0.5,<0.004,<0.001; Eating in Public, <0.2,<0.002,<0.03; Understandability of Speech, <0.9,<0.001,<0.001; Speaking in Public, <0.4,<0.03,<0.001; MDADI, <0.4,<0.005,<0.01; Single Word Intelligibility, <0.4,<0.1,<0.001; Sentence Intelligibility, <0.5,<0.08,<0.001; Words Per Minute Intelligibility, <0.6,<0.04,<0.001; Sentence Efficiency Ratio, <0.4,<0.03,<0.002. Proportion of patients by 4 defect groups who underwent: tissue transplantation, 51%,93.9%,100%,100%.Radiation,24%,67%,88%,80%.Between hemiglossectomy and extended hemiglossectomy, the defect extends into the contralateral floor of the mouth and/or the anterior tonsillar pillar; resection of these subunits limits tongue mobility with an impact on functional outcome and MDADI. Between extended hemiglossectomy and oral glossectomy, the defect extends to include the tip of the tongue and appears to impact functional outcome and MDADI. ConclusionsSubtotal hemiglossectomy, hemiglossectomy, extended glossectomy and oral glossectomy are associated with quantitative (elevation, protrusion, open mouth premaxillary contact and obliteration), qualitative (speech and swallowing) and MDADI differences, suggesting that these 4 ordinal defect groups are distinct.

Patient-reported Quality of Life After Breast-conserving Surgery With Radiotherapy Versus Mastectomy and Reconstruction.

To compare long-term quality of life (QOL) outcomes in breast cancer survivors who received breast-conserving surgery with radiotherapy (BCS+RT) with those who received a mastectomy and reconstructive surgery (Mast+Recon) without radiotherapy and identify other important factors. The long-term differences in patient-reported QOL outcomes following BCS+RT and Mast+Recon are not well understood. We identified patients from the Texas Cancer Registry with stage 0-II breast cancer diagnosed in 2009-2014 after BCS+RT or Mast+Recon without radiotherapy. Sampling was stratified by age and race and ethnicity. A paper survey was sent to 4800 patients which included validated BREAST-Q and PROMIS modules. Multivariable linear regression models were implemented for each outcome. Minimal clinically important difference for BREAST-Q and PROMIS modules, respectively, was 4 points and 2 points. Of 1215 respondents (25.3% response rate), 631 received BCS+RT and 584 received Mast+Recon. The median interval from diagnosis to survey completion was 9 years. In adjusted analysis, Mast+Recon was associated with worse BREAST-Q psychosocial well-being (effect size: -3.80, P =0.04) and sexual well-being (effect size: -5.41, P =0.02), but better PROMIS physical function (effect size: 0.54, P =0.03) and similar BREAST-Q satisfaction with breasts, physical well-being, and PROMIS upper extremity function ( P >0.05) compared with BCS+RT. Only the difference in sexual well-being reached clinical significance. Older (≥65) patients receiving BCS+RT and younger (<50) patients receiving autologous Mast+Recon typically reported higher QOL scores. Receipt of chemotherapy was associated with detriments to multiple QOL domains. Patients who underwent Mast+Recon reported worse long-term sexual well-being compared with BCS+RT. Older patients derived a greater benefit from BCS+RT, while younger patients derived a greater benefit from Mast+Recon. These data inform preference-sensitive decision-making for women with early-stage breast cancer.

Genitourinary Quality-of-Life Comparison Between Urethral Sparing Prostate Stereotactic Body Radiation Therapy Monotherapy and Virtual High-Dose-Rate Brachytherapy Boost

Although radiation dose escalation improves prostate cancer disease control, it can cause increased toxicity. Genitourinary (GU) symptoms after prostate radiation therapy affect patient health-related quality of life (QoL). We compared patient-reported GU QoL outcomes following 2 alternative urethral sparing stereotactic body radiation therapy regimens. Expanded Prostate Cancer Index Composite (EPIC)-26 GU scores were compared between 2 urethral sparing stereotactic body radiation therapy trials. The SPARK trial prescribed a "Monotherapy" dose of 36.25 Gy in 5 fractions to the prostate. The PROMETHEUS trial prescribed 2 phases: a 19- to 21-Gy in 2 fractions "Boost" to the prostate, followed by 46 Gy in 23 fractions or 36 Gy in 12 fractions. The biological effective dose (BED) for urethral toxicity was 123.9 Gy for Monotherapy and 155.8 to 171.2 Gy for Boost. Mixed effects logistic regression models were utilized to estimate the difference in the odds of a minimal clinically important change from baseline EPIC-26 GU score between regimens at each follow-up. 46 Monotherapy and 149 Boost patients completed baseline EPIC-26 scoring. Mean EPIC-26 GU scores revealed statistically superior urinary incontinence outcomes for Monotherapy at 12 months (mean difference, 6.9; 95% confidence interval [CI], 1.6-12.1; P=.01) and 36 months (mean difference, 9.6; 95% CI, 4.1-15.1; P < .01). Monotherapy also revealed superior mean urinary irritative/obstructive outcomes at 12 months (mean difference, 6.9; 95% CI, 2.0-12.9; P < .01) and 36 months (mean difference, 6.3; 95% CI, 1.9-10.8; P < .01). For both domains and at all time points, the absolute differences were <10%. There were no significant differences in the odds of reporting a minimal clinically important change between regimens at any time point. Even in the presence of urethral sparing, the higher BED delivered in the Boost schedule may have a small adverse effect on GU QoL compared with Monotherapy. However, this did not translate to statistically significant differences in minimal clinically important changes. Whether the higher BED of the boost arm offers an efficacy advantage is being investigated in the Trans Tasman Radiation Oncology Group 18.01 NINJA randomized trial.

Initial results of a phase 2 pilot study of radium-223 and radiotherapy in untreated hormone-naïve men with oligometastatic prostate cancer to bone.

156 Background: We hypothesized that treatment with Radium-223 (Ra223) and to ≤5 sites of bony metastases (mets) could safely delay the time to start androgen deprivation therapy (ADT) and maintain quality of life (QoL). Methods: 20 men previously treated with surgery, radiation, or both for M0 PCa later developed ≤5 bone-only mets were eligible for this prospective trial. Inclusion: testosterone ≥ 100 ng/dL and mets on conventional bone scan, validated by a CT, MRI, or PET/CT. Exclusion: LHRH therapies after initial treatment, or N1 disease at diagnosis of bone mets. Therapy was 6 cycles of Ra223 and SBRT (30 Gy in 5 fractions between cycles 1-2). Bone scan was performed at baseline and q3 months. PSA was evaluated monthly during the Ra223 course, and q3 months after. Therapeutic effectiveness was defined as ≥20% of patients meeting the primary endpoint of freedom from ADT (FFAdt) use at 15 months. Discontinuation of study therapy occurred if: PSA rise &gt; 10% if baseline PSA &gt;20ng/ml, PSA&gt;20 if baseline PSA &lt;20 ng/ml, radiographic progression or a skeletal-related event (SRE). All endpoints were timed from the Cycle 1 radium date. Patients were followed for 2 years. Clinically significant changes in patient-reported outcome (PRO) measures were defined as &gt;1/2 standard deviation from the mean baseline value and were censored after the time of ADT use. Continuous and categorical covariates were compared using the Wilcoxon rank sum and Pearson’s Chi2 tests, respectively, and univariate Cox regression. Statistical significance was considered at P&lt;0.05. Results: The median number of Ra223 cycles was 6. 6 patients had &lt;6 cycles (range 2-5) due to progression. FFAdt at 15 and 24 Months was 49.5% and 38.5%, respectively (p&lt;0.001). The median time to ADT was 14.8 months. There were no significant changes from baseline in any PRO QoL domain (physical functioning, anxiety, depression, fatigue, satisfaction with participation in social roles, sleep disturbance, and pain interference). There were 2 patients with Grade 3 SREs (bone fracture, pain). Grade 2+ events attributed as possible or likely to Ra-223 were seen in 4 patients (bone pain, fatigue, fracture, decreased WBC count, and other). Grade 2+ events attributed as possible or likely to EBRT were seen in 2 patients and included fatigue and other pain. were noted for age, baseline PSA, days from primary treatment, NCCN risk group, TNM stage, ISUP grade group, BMI, or # of lesions in those who met or failed the primary endpoint (all p&gt;0.05). Conclusions: First-line use of Ra223 and SBRT to oligomets in hormone-naïve men in this prospective pilot study resulted in a significant delay in ADT use compared to historical control, is well tolerated, and maintains QoL. Clinical trial information: NCT03304418 .

Sickle Cell Trevor Thompson Transition Project (ST3P-UP) protocol for managing care transitions: Methods and rationale

BackgroundEmerging adults with sickle cell disease (EASCD) experience significant challenges transitioning from pediatric to adult care. Acute care utilization increases, quality of life (QOL) declines, with an increased risk of mortality. Currently, there are no practice standards to guide emerging adults through the transition process. We are creating a structured transition education (STE) based program for EASCD by customizing the Six Core Elements (6 CE) of Health Care Transition model and are evaluating the effectiveness of adding peer mentoring (PM). MethodsThe Sickle Cell Trevor Thompson Transition Project (ST3P-UP) is an ongoing multi-site, cluster randomized clinical trial with a target enrollment of 537 EASCD aged 16 to 25 years in pediatric care. Each site (n = 14) comprises a pediatric clinic, adult clinic, and a sickle cell disease (SCD) community-based organization (CBO). Sites are randomized 1:1 to either STE or STE + PM. EASCDs are followed prospectively for 24 months. Rapid cycle plan-do-study-act quality improvement (QI) methods are used to implement the STE. The primary objective is to compare the effectiveness of STE + PM versus STE only at decreasing the number of acute care visits per year over 24 months. The secondary objectives are to compare overall healthcare utilization and patient-reported QOL outcomes at 24 months. ConclusionWe aim to demonstrate the feasibility of using a QI approach to implement 6 CE-based practice standards at 14 disparate SCD clinical programs to guide EASCD through the transition process. We hypothesize that adding PM to the STE program will improve acute care reliance, QOL, and satisfaction with transition outcomes.

Multi-Center Quality of Life Outcomes for Patients with Acoustic Neuromas Treated with a Non-Invasive Stereotactic Radiosurgery Instrument and Linear Accelerator-Based Radiosurgery

<h3>Purpose/Objective(s)</h3> Prior studies have reported favorable local control for patients treated with Gamma Knife (GK) or linear accelerator (LINAC)-based radiosurgery (SRS); however, direct comparison of detailed patient-reported quality of life (QOL) outcomes are lacking. This multi-center retrospective review assessed for differences in QOL outcomes and toxicity profiles after radiotherapy for acoustic neuromas in patients treated with GK and LINAC-based radiosurgery. <h3>Materials/Methods</h3> In this multi-center single institution analysis, we retrospectively reviewed acoustic neuroma cases treated with either GK or LINAC-based SRS between 2008-2017. We compared pre- and post- treatment clinical outcomes including new development of tinnitus, vertigo, gait disturbance, facial palsy, hydrocephalus and audiometric data. We also collected radiographic and dosimetric information including tumor size and dose to cochlea. Descriptive statistics were performed and χ² was utilized to assess for intergroup differences in clinicoradiographic or dosimetric differences. Univariate and multivariate multinomial logistic regression analyses were performed with backward selection at alpha of 0.2 to assess for statistically significant associations with the development of the clinical endpoints described above. <h3>Results</h3> A total of 85 patients were included in our review, 36 in the GK group and 49 in the LINAC-SRS group. 39 patients were male (45.9%) and 46 female (54.1%), 45 were left-sided tumors (52.9%) and 40 right-sided tumors (47.1%). All patients were treated with single-fraction SRS, with a prescription of 12.5 Gy for GK and 12 Gy for LINAC-based SRS. Median follow up was 25 months (median 21 months in GK group, 26 months in LINAC group). On multivariate analysis, there was no significant difference in the development of post-treatment tinnitus, vertigo, gait disturbance, facial palsy, hydrocephalus, change in Gardner Robertson Grade, or change in hearing between the GK and LINAC treatment groups (p> 0.05). Similarly, multivariate analysis did not show tumor size or cochlear dose to be associated with development of specific toxicities between treatment modalities (p>0.05). <h3>Conclusion</h3> This multi-center retrospective review found no significant differences in patient-reported QOL outcomes for patients treated with either Gamma Knife or LINAC-based radiosurgery for acoustic neuromas. This study adds to the body of evidence that both modalities are feasible approaches with similar toxicity profiles for the treatment of acoustic neuromas, and patients can be counselled as such.

Dynamic Change in Patient Reported Quality of Life is a Predictor for Survival in Localized Prostate Cancer: Exploratory Analysis from a Phase III Randomized Controlled Trial

<h3>Purpose/Objective(s)</h3> Patient reported quality of life (QOL) outcomes are pivotal endpoints to determine treatment efficacy and safety. However, it remains unknown if treatment induced change in patient reported QOL outcomes correlate with survival in localized prostate cancer (LPCa). We performed an exploratory analysis of a phase III randomized controlled study to determine the association of treatment induced dynamic change in patient reported global QOL with long-term overall survival (OS) and disease-free survival (DFS) in LPCa treated with radiotherapy (RT) and androgen deprivation therapy (ADT). <h3>Materials/Methods</h3> LPCa patients with Gleason score ≤7, clinical stage T1b-T3a, and PSA <30 ng/mL were randomized to neoadjuvant and concurrent ADT for 6 mos starting 4 mos before prostate RT or concomitant and adjuvant ADT for 6 mos starting concurrently with RT. Patient reported QOL outcomes were collected using EORTC QOL questionnaires. We used the global QOL (G-QOL) score from C30 questionnaire. Increase in G-QOL score indicated improvement in global QOL. To capture the association between the dynamic change in the G-QOL of each patient and the hazard of outcome, we utilized the framework of multivariate joint modeling for longitudinal and survival outcomes. For the time-to-event submodel, a Cox proportional hazard regression model was built with covariables including treatment arm, baseline PSA, tumor stage, Gleason score, and age. For the longitudinal submodel, a linear mixed effect model was built with an interaction term for treatment arm and time of evaluation in addition to fixed covariables - treatment arm, time of evaluation, baseline G-QOL score and age. Time of assessment was included as a random slope while patients were included as random intercepts in the mixed models. The two submodels were linked through a random effect. Baseline hazard was modeled using penalized splines. A two-sided p-value <0.025 was chosen to be the threshold for statistical significance. <h3>Results</h3> A total of 388 patients were eligible for this study – 191 belonged to the neoadjuvant arm while 197 to the adjuvant arm. At a median follow-up of 148 mos, a total of 133 deaths were recorded. On joint modelling, an increase in G-QOL score by 10 units (the threshold for clinically meaningful change) was associated with a 11.2% decrease in the hazard of death (hazard ratio [HR] per 1 unit increase G-QOL: 0.988, 95% CI: 0.980-0.996; p=0.007). An increase in G-QOL score by 10 units was associated with 10% decrease in the hazard of progression or death (HR per 1 unit increase in G-QOL: 0.990; 95% CI: 0.984-0.999; p=0.023). <h3>Conclusion</h3> Treatment induced improvement in global QOL is a predictor for improved DFS and OS in LPCa. This suggests a significant interplay of patient-reported quality of life and quantity of life in LPCa which could mainly be driven by the non-cancer specific mortality in this patient population. Judicious use of these QOL metrics could guide risk stratification and potentially inform treatment decision in these patients

Early Clinical Effectiveness, Toxicity and Quality of Life Outcomes of Magnetic Resonance Imaging-Guided Stereotactic Ablative Radiotherapy: A Systematic Review

<h3>Purpose/Objective(s)</h3> Magnetic resonance imaging-guided stereotactic ablative radiotherapy (MRgSABR) is postulated to further improve the therapeutic ratio of stereotactic radiotherapy by increasing the certainty of dose delivery. As early phase data on MRgSABR have rapidly accumulated, we systematically reviewed the existing literature to summarize the clinical outcomes, toxicity and patient-reported outcomes following MRgSABR. <h3>Materials/Methods</h3> This systematic review was conducted in accordance with consensus guidelines (PROSPERO: CRD42021277584). The PubMed, Embase, and Cochrane Library databases were queried from January 2014 to August 2021. Studies in the English language that evaluated the local control (LC), overall survival (OS), clinician-reported toxicity or patient-reported quality of life outcomes of MRgSABR were included. Reviews or guidelines that did not contribute new results, studies with <=3 total patients, and studies where MRgSABR results could not be disaggregated from radiotherapy using non-MR platforms were excluded. Results were summarized using medians and ranges. <h3>Results</h3> We reviewed 849 studies, with 34 (1148 patients) meeting all inclusion criteria. Most studies (56%) were retrospective in nature, with the remaining being prospective single-arm studies. Median follow-up ranged from 4 to 25 months. Liver, prostate, and pancreas were the most common sites for MRgSABR studies. LC was 57-96% (median: 88%) at 1 year and 59-100% (median: 80%) at 2 years after liver MRgSABR (11 studies, 199 patients). OS post-liver MRgSABR was 69-93% (median: 80%) at 1 year and 46-60% (median: 51%) at 2 years. Grade 3 toxicity was 0-8% and no grade 4+ toxicity was reported for the liver. For prostate MRgSABR (6 studies, 282 patients), biochemical control was 75-100% (median: 97%) at a median follow-up of 6 to 12 months. Grade 3+ toxicity was 0-2% and patients reported temporarily increased urinary symptoms during prostate MRgSABR that resolved after treatment. For pancreatic MRgSABR (6 studies, 304 patients), LC was 57-95% (median: 86%) at 1 year and 59-83% (median: 77%) at 2 years. OS was 59-82% (median: 69%) at 1 year and 38-52% (median: 45%) at 2 years after pancreatic MRgSABR. The risk of acute grade 3+ toxicity was 0-4% and the risk of late grade 3+ toxicity was 3-13% following pancreatic MRgSABR. Remaining studies that reported on a variety of treatment sites showed good LC of 72-96% at 1 year (median: 92%). Grade 3+ toxicity was <=5% except for lung (8-20%) and head and neck MRgSABR (43%). <h3>Conclusion</h3> Early data on MRgSABR indicate good LC and tolerability across multiple clinical scenarios, though noticeable toxicity was observed in certain treatment sites. Prospective comparative clinical trials are needed to quantify the improvement in clinical outcomes with MRgSABR relative to non-MR-guided radiotherapy technologies.