Quality of Life After Definitive Linear Accelerator-based Stereotactic Radiotherapy for Prostate Cancer: a Longitudinal Study

Background: Prostate cancer is the second most common malignancy worldwide, and the majority of patients are diagnosed with localized disease. We examined patients’ quality of life after stereotactic body radiation therapy (SBRT) for prostate cancer. Method: We included patients who were treated between 2016 and 2020. Inclusion criteria were adenocarcinoma of the prostate; class risk of low, intermediate, and high; and a World Health Organization performance status of 0–2. Quality of life was measured using the Functional Assessment of Cancer Therapy-Prostate (FACT-P). Results: A total of 439 patients were treated with SBRT, with a median age of 73 years old. The median follow-up period was 34 months. FACT-P Trial Outcome Index (p < 0.0001), FACT-General (p = 0.0003), and FACT-P-Total (p < 0.0001) scores declined at 1 month post-SBRT, then recovered and returned to the same level as before treatment at 3–4 months post-SBRT. The decrease in quality of life in the first month was particularly remarkable in patients who received long-term hormone injections (36%). One month after the end of SBRT, about 22% of patients experienced "quite a bit” or more troubling side effects. Conclusions: This study showed longitudinal changes in quality of life by FACT-P after SBRT for prostate cancer. Overall, prostate SBRT was well tolerated.

Health-related quality of life (HRQoL) in patients (pts) with myelodysplastic syndromes (MDS) in the Connect Myeloid Disease Registry.

7040 Background: At diagnosis, disease risk and transfusion burden (TB) can impact HRQoL in pts with MDS. The impact of disease status and higher transfusion requirements on HRQoL has not been well studied. We used data from the Connect Myeloid Disease Registry, an ongoing, prospective, observational cohort study that includes adult pts with lower-risk (LR) and higher-risk (HR) MDS, to investigate factors influencing baseline (BL) and subsequent HRQoL. Methods: BL and Month 6 (M6) data from pts enrolled from Dec 12, 2013 to Mar 6, 2020 (data cutoff) were analyzed. Pts were stratified by International Prognostic Scoring System (IPSS) risk (LR, HR), treatment (Tx) within 45 days post-enrollment (no Tx, best supportive care [BSC], active Tx), and TB 16 weeks post-BL (non-transfusion dependent [NTD], low TB [LTB]; 1−3 transfusions, high TB [HTB]: ≥4 transfusions). Pts completed EQ-5D, FACT-An trial outcome index (TOI), and FACT-Fatigue (FACT-F) questionnaires at BL and quarterly thereafter. Clinically meaningful change, based on minimally important differences, was defined as a change of ±0.07 for EQ-5D, ±6 for FACT-An TOI, and ±3 for FACT-F. Results: At data cutoff, 830 (489 LR, 341 HR) pts were enrolled. Median age was 74 years. 278 pts received no initial Tx, 161 BSC, and 378 active Tx. At BL, 470 were NTD, 197 LTB, and 163 HTB. Of 670 pts still on-study at M6, 462 completed the questionnaires at both BL and M6. At BL , clinically meaningful differences were observed in FACT-An TOI and FACT-F scores, but not EQ-5D, between LR- and HR-MDS and the Tx subgroups . From BL to M6, no clinically meaningful changes were observed in mean scores for each questionnaire. For the TB subgroups, meaningful differences were observed at BL in FACT-An TOI and FACT-F scores, but not EQ-5D (Table). From BL to M6, meaningful decreases in scores were reported by 26%, 30%, and 35% of NTD, LTB, and HTB pts in EQ-5D, 41%, 43%, and 48% for FACT-An TOI, and 40%, 42%, and 48% for FACT-F; increases were reported by 19%, 19%, and 20% pts for EQ-5D, 31%, 32%, and 39% for FACT-An TOI, and 30%, 39%, and 40% for FACT-F. Conclusions: This preliminary analysis suggests that pts with HR-MDS, and transfusion-dependent pts, generally had worse HRQoL at BL, providing further support to initiating active Tx in pts with TB. Possible limitations of the analysis are lower completion rates in pts with more severe disease, and EQ-5D may not capture changes in these subgroups at M6. A longer follow-up may help delineate the impact of Tx on HRQoL assessments in pts with MDS. Clinical trial information: NCT01688011. [Table: see text]

Quality-of-life (QOL) analyses in patients with multiple myeloma: Results from the selinexor (KPT-330) treatment of refractory myeloma (STORM) phase IIb study.

e20522 Background: Selinexor, a novel oral selective inhibitor of nuclear export, was recently approved for use in relapsed/refractory multiple myeloma (MM). The efficacy and safety of selinexor and dexamethasone was evaluated in a phase 2b, single-arm, open-label, multicenter trial in patients with penta-exposed, triple-class refractory MM. Patient-reported outcomes were measured using the Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) assessment. While minimal clinically important differences (MCID) have been established for other FACT scales, there is no known, validated definition of MCID for the FACT-MM. This study reports results of QoL analyses in patients with MM enrolled in the STORM phase 2b trial and examines two approaches to calculate MCID for the FACT-MM. Methods: FACT-MM data were collected at baseline, on day 1 of each 4-week cycle, and at end of treatment (EOT) during the STORM phase 2b trial. Change from baseline was analyzed for the FACT-MM total score, FACT-trial outcome index (TOI), FACT-General (FACT-G), and the MM-specific domain. Two approaches for evaluating MCID were explored: the first based on patient-reported assessment of meaningful change, defined as 10% of the instrument range (Ringash 2007), and the second based on mean baseline differences between ECOG groups (0 vs 1 to 2) based on patient level data. Additional analyses were performed to identify trends among treatment responders and non-responders, including a difference-in-difference (DID) analysis to compare changes between baseline and EOT. Results: Eighty patients had sufficient data to be included in longitudinal QOL analyses. MCID analyses demonstrated that most patients did not experience decline during the first six cycles of treatment; this pattern was consistent with MCID defined either as 10% of the instrument range (range 54% to 75% of patients), or as an ECOG-based anchor (range: 54% to 73% of patients). The DID analysis found that the mean change in QoL of non-responders decreased significantly between baseline and EOT, while responders had no significant change. This difference between responders and non-responders was significant for the FACT-G. Conclusions: Most patients did not experience QoL decline during the early cycles of selinexor treatment during the STORM 2b trial. The MCID decline, evaluated by two approaches, was greater among treatment non-responders than responders. A DID approach demonstrated greater decline between baseline and EOT for non-responders. Clinical trial information: NCT02336815.

Health-related quality of life (HRQoL) patient-reported outcomes (PROs) and survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts).

53 Background: HRQoL is a relevant endpoint in trials in advanced prostate cancer. An association between HRQoL and OS has been reported. The Functional Assessment of Cancer Therapy-Prostate (FACT-P) is a validated HRQoL PRO in mCRPC. Methods: We evaluated the association between FACT-P and OS in the COU-301 and COU-302 trials (abiraterone vs placebo in mCRPC pts). FACT-P scores, sub-scores (physical (PWB), emotional (EWB), functional (FWB), social (SWB) well-being, prostate cancer subscale (PCS) FACT-G and the Trial Outcome Index (TOI) were calculated. A decrease in 3 (PWB, EWB, SWB, FWB, PCS), 9 (FACT-G, TOI) or 10 (FACT-Total) points after 3 cycles was considered clinically relevant. The association between FACT-P and OS was evaluated with Kaplan-Meier, Cox-regression models and c-indices. Results: 2,177 pts (COU-301: 1,121 /COU-302: 1,056) had valid baseline (BL) FACT-P scores. Mean BL score was 106.6 (COU-301) and 122.3 (COU-302). BL total scores were associated with OS in both COU-AA-301 (p<0.001) and COU-302 (p<0.001), independent of treatment. All FACT-P sub-scores except SWB were associated with OS (Table). A decrease in FACTP scores was associated with decreased OS in COU-301 (19.6 vs 14.2m; HR: 1.8; p<0.001) and COU-302 (34.4 vs 27.7m; HR: 1.3; p=0.009) datasets. Conclusions: BL FACTP scores (except SWB subscale) are significantly associated with outcome. Early declines in HRQoL can be observed and are associated with worse outcome. Prospective evaluation of the significance of changes in HRQoL is needed. YODA Project 2018-3745.[Table: see text]

Actigraphy as an assessment of performance status in patients with advanced lung cancer

ObjectiveWearable devices such as a wrist actigraph may have a potential to objectively estimate patients’ functioning and may supplement performance status (PS). This proof-of-concept study aimed to evaluate whether actigraphy data are significantly associated with patients’ functioning and are predictive of their survival in patients with metastatic non-small cell lung cancer.MethodWe collected actigraphy data for a three-day period in ambulatory patients with stage IV non-small cell lung cancer. We computed correlations between actigraphy data (specifically, proportion of time spent immobile while awake) and clinician-rated PS, subjective report of physical activities, quality of life (the Functional Assessment of Cancer Therapy – Trial Outcome Index), and survival.ResultActigraphy data (the proportion of time awake spent immobile) were significantly correlated with Functional Assessment of Cancer Therapy – Trial Outcome Index (r = −0.53, p < 0.001) and with the Eastern Cooperative Oncology Group PS (ECOG PS) (r = 0.37, p < 0.001). The proportion of time awake spent immobile was significantly associated with worse survival. For each 10% increase in this measure, the hazard ratio (HR) was 1.48 (95% confidence interval [CI95%] = 1.06, 2.06) for overall mortality, and odds ratio was 2.99 (CI95% = 1.27, 7.05) for six-month mortality. ECOG PS was also associated with worse survival (HR = 2.80, CI95% = 1.34, 5.86). Among patients with ECOG PS 0-1, the percentage of time awake spent immobile was significantly associated with worse survival, HR = 1.93 (CI95% = 1.10, 3.42), whereas ECOG PS did not predict survival.Significance of ResultsActigraphy may have potential to predict important clinical outcomes, such as quality of life and survival, and may serve to supplement PS. Further validation study is warranted.

Quality of life and quality-adjusted time without toxicity in palliatively treated head-and-neck cancer patients

Background: Quality-adjusted time without toxicity (Q-TWiST) and quality of life (QOL) are indicators of benefit provided by different chemotherapy regimens. Methods: This was a prospective study, in which adult head-and-neck (H and N) cancer patients, treated with metronomic chemotherapy were enrolled. The Functional Assessment of Cancer Therapy-General H and N (FACT-G and H and N) version 4 pro formas were self-administered before the start of chemotherapy and then at 2, 4, and 6 months. FACT QOL and Q-TWiST analysis were then performed. Results: There was an improvement in the social well-being (P = 0.370), emotional well-being (P = 0.000), functional well-being (P = 0.000), H and N cancer subscale (P = 0.001), FACT H and N trial outcome index (P = 0.000), FACT G-total score (P = 0.000), and FACT H and N total score (P = 0.000) with palliative chemotherapy. The QTWiST value for a utility score of 0.25 for toxicity and relapse state was 145.93 days. Conclusion: Metronomic chemotherapy is associated with improvement in QOL and has a low duration of time spent in toxicity state.

Patient-Reported Toxicity During Pelvic Intensity-Modulated Radiation Therapy: NRG Oncology–RTOG 1203

Purpose NRG Oncology/RTOG 1203 was designed to compare patient-reported acute toxicity and health-related quality of life during treatment with standard pelvic radiation or intensity-modulated radiation therapy (IMRT) in women with cervical and endometrial cancer. Methods Patients were randomly assigned to standard four-field radiation therapy (RT) or IMRT radiation treatment. The primary end point was change in patient-reported acute GI toxicity from baseline to the end of RT, measured with the bowel domain of the Expanded Prostate Cancer Index Composite (EPIC). Secondary end points included change in patient-reported urinary toxicity, change in GI toxicity measured with the Patient-Reported Outcome Common Terminology Criteria for Adverse Events, and quality of life measured with the Trial Outcome Index. Results From 2012 to 2015, 289 patients were enrolled, of whom 278 were eligible. Between baseline and end of RT, the mean EPIC bowel score declined 23.6 points in the standard RT group and 18.6 points in the IMRT group ( P = .048), the mean EPIC urinary score declined 10.4 points in the standard RT group and 5.6 points in the IMRT group ( P = .03), and the mean Trial Outcome Index score declined 12.8 points in the standard RT group and 8.8 points in the IMRT group ( P = .06). At the end of RT, 51.9% of women who received standard RT and 33.7% who received IMRT reported frequent or almost constant diarrhea ( P = .01), and more patients who received standard RT were taking antidiarrheal medications four or more times daily (20.4% v 7.8%; P = .04). Conclusion Pelvic IMRT was associated with significantly less GI and urinary toxicity than standard RT from the patient’s perspective.

Five-year quality of life assessment after carbon ion radiotherapy for prostate cancer

The aim of this study was to prospectively assess 5-year health-related quality of life (HRQOL) of patients treated with carbon ion radiotherapy (C-ion RT) for clinically localized prostate cancer. A total of 417 patients received carbon ion radiotherapy at a total dose of 63–66 Gray-equivalents (GyE) in 20 fractions over 5 weeks, and neoadjuvant and adjuvant androgen deprivation therapy (ADT) were administered for intermediate and high-risk patients. A HRQOL assessment was performed at five time points (immediately before the initiation of C-ion RT, immediately after, and at 12, 36 and 60 months after completion of C-ion RT) using Functional Assessment of Cancer Therapy (FACT) questionnaires. FACT-G and FACT-P scores were significantly decreased; however, the absolute change after 60 months was minimal. The transient decreases in the Trial Outcome Index (TOI) score returned to their baseline levels. Use of ADT, presence of adverse events, and biochemical failure were related to lower scores. Scores of subdomains of FACT instruments indicated characteristic changes. The pattern of HRQOL change after C-ion RT was similar to that of other modalities. Further controlled studies focusing on a HRQOL in patients with prostate cancer are warranted.

Primary Results of the Health-Related Quality of Life Assessment from the Phase III Gadolin Study of Obinutuzumab Plus Bendamustine Compared with Bendamustine Alone in Patients with Rituximab-Refractory, Indolent Non-Hodgkin Lymphoma

Background Meaningful improvement in, or maintenance of, pre-treatment health-related quality of life (HRQoL) is important for rituximab-refractory (R-ref), indolent non-Hodgkin lymphoma patients. GADOLIN (NCT01059630) is an open-label, phase III study of bendamustine (B) with or without obinutuzumab (GA101; Gazyva/Gazyvaro; G) in patients with CD20+ R-ref, indolent non-Hodgkin lymphoma. In GADOLIN, independent review facility (IRF)-assessed median progression-free survival (PFS) was 14.9 months (mo) in the B arm and not reached in the G-B arm (HR=0.55; 95% CI, 0.40, 0.74; p=0.0001), with an acceptable safety profile. Here, we present patient-reported HRQoL data from GADOLIN. Methods The Functional Assessment of Cancer Treatment-Lymphoma (FACT-Lym) questionnaire (Webster K, et al. Qual Life Res 2005;14:2103) was used to assess overall HRQoL, physical and functional well-being, and disease- and treatment-related symptoms. It was administered on day 1 of cycles 1, 3 and 5 during treatment, at the end of induction (EOI) treatment and every other month for 2-years (where non-progressing G-B patients received G maintenance and B patients were observed), and during follow-up. Time to ³6 point worsening from baseline in the FACT-Lym Trial Outcome Index (TOI) was estimated for each treatment group using a Kaplan-Meier curve. Minimally important differences at the individual subscale and total score levels were used to define the proportion of patients reporting improvement on the FACT-Lym lymphoma subscale (³3 points), TOI (³6 points), and lymphoma total score (³7 points). Results The primary study analysis was undertaken when 396 patients had been randomized (194 to G-B and 202 to B [198 treated]); median observation time was 21 mo. Baseline characteristics were balanced between arms. Median age was 63 years and patients had a median of two prior therapies. Questionnaire completion rates were generally good and balanced in the G-B vs B arms (91.2% vs 89.1% at baseline, 74.2% vs 69.8% at EOI, and 33.0% vs 31.2% at final follow up, respectively). Time to ³6 point worsening from baseline on the FACT-Lym TOI was 8.0 mo (95% CI, 5.8, 15.1) in the G-B arm and 4.6 mo (95% CI, 3.8, 6.4) in the B arm (HR, 0.74; 95% CI, 0.56, 0.98; Figure 1). In addition, a greater proportion of patients reported meaningful improvement on the lymphoma subscale, lymphoma TOI, and total score in the G-B arm than in the B arm throughout the study (Table 1). Conclusions G combined with B, followed by G maintenance, resulted in a greater proportion of patients reporting a meaningful improvement in HRQoL throughout the course of the study. This improvement occurred even during induction, despite similar clinical response rates. A longer time to clinically meaningful deterioration of lymphoma-related HRQoL compared with patients who received B alone was also observed. These results are consistent with the improvement in PFS and suggest that the improvement in PFS is not at the expense of an increase in treatment-related toxicity that could lead to a reduction in a patient's HRQoL. Figure 1. Kaplan-Meier Plot of FACT-Lym Trial Outcome Index ³ 6 point worsening from Baseline (ITT population) Figure 1. Kaplan-Meier Plot of FACT-Lym Trial Outcome Index ³ 6 point worsening from Baseline (ITT population) Figure 2. Summary of Definitive Improvement in FACT-Lym (ITT population) Figure 2. Summary of Definitive Improvement in FACT-Lym (ITT population) Disclosures Cheson: Celgene: Consultancy, Research Funding; AstraZeneca: Consultancy; Gilead: Consultancy, Research Funding; Spectrum: Consultancy; MedImmune: Research Funding; Teva: Research Funding; Pharmacyclics: Consultancy, Research Funding; Ascenta: Research Funding; Roche/Genentech: Consultancy, Research Funding; Astellas: Consultancy. Off Label Use: Obinutuzumab (GA101; Gazyva/Gazyvaro) is a CD20-directed cytolytic antibody and is indicated, in combination with chlorambucil, for the treatment of patients with previously untreated chronic lymphocytic leukemia). This abstract reports on bendamustine with or without obinutuzumab in patients with CD20+ R-ref, indolent non-Hodgkin lymphoma.. Trask:Genentech: Employment. Gribben:Janssen: Honoraria; Pharmacyclics: Honoraria; Celgene: Consultancy, Honoraria; Gilead: Honoraria; Roche/Genentech: Honoraria. Dimier:Roche: Employment. Kimby:Pfizer: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Jansen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lugtenburg:Mundipharma: Consultancy; Servier: Consultancy; Janssen-Cilag: Consultancy; Celgene: Consultancy; Roche: Consultancy. Thieblemont:St. Louis Hospital, Paris, France: Employment. Wassner Fritsch:Roche: Employment. Sehn:Roche/Genentech: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria.