Bendamustine

The health states were designed to describe the functional and patient-centred impacts of CLL and it treatment, rather than clinical descriptions of the disease, in line with published guidelines for health state development [15 (link)]. Development was an iterative process that involved incorporating input from the literature, patient web-based discussion forums, physicians with expertise in CLL, and patients with CLL.
The following domains were described, enabling balanced descriptions across the health states: cancer description, "cancer of the blood"; treatment response category; swollen glands in neck, armpits, or groin; limitations in performing daily activities; level of fatigue; appetite; and trouble sleeping because of night sweats. These domains are those that previous researchers have identified as important in CLL. In a review of the burden and outcomes associated with leukaemia, for example, Redaelli et al [16 (link)] reported that physical functioning, role-functioning, and fatigue/energy levels were among the most important domains related to CLL. With regard to symptoms, Kermani et al [17 (link)] found that, in CLL patients, fatigue was the most common (present in 54% of patients), followed by dyspnoea (32%), abdominal pain (29%), and weight loss (22%). In addition, lymphadenopathy (enlarged lymph nodes in the groin, spleen, or neck) was observed in 89% of patients. Other researchers [18 (link),19 (link)] also have reported that, compared to population norms, CLL patients have more complaints about fatigue, appetite loss, and sleep disturbances. Based on patient posts on the web-based CLL forums, frequent and bothersome impacts of CLL were related to fatigue/energy levels, ability to perform daily activities, appetite disturbances, sleep disturbances, and noticeably enlarged lymph nodes.
In all, four CLL treatment-related response states, six toxicity-related health states, and two health states reflecting the impact of undergoing a second or third course of treatment were developed (health states located in Additional File 1). The domains describing clinical response status were based on the National Cancer Institute Working Group (NCIWG)'s treatment response definitions for CLL [20 (link)]. The complete response state was based on the complete absence of symptoms; partial response represented a ≥ 50% reduction in symptoms; no change meant that the disease was stable (i.e., symptoms not worsening or improving); and progressive disease indicated that symptoms were worsening.
With respect to the toxicity states, these were identified based on common toxicities experienced with bendamustine and chlorambucil, and draft descriptions were developed using the Cancer Therapy Evaluation program's Common Terminology Criteria version 3.0 [21 ]. Because it would be too cumbersome for respondents to value all possible combinations of clinical response status with the various possible toxicities, the toxicity health states described each toxicity in association with the base health state of no change (NC) health state. NC was selected to pair with the toxicities as opposed to PR given that this is a more conservative approach; if the toxicities were coupled with PR, for example, it is possible that respondents would not rate them as poorly as they would if they were coupled with NC because they may be more accepting of an aggressive therapy if they know that the treatment is working.
The draft health states were refined after iterative review by four independent clinicians. Draft health states were tested in five Scottish CLL patients recruited through the CLL Support Association, a web-based support group based in the UK, and final revisions were made based on their feedback. The states were developed to be easily comprehensible from the general public's perspective and gender-neutral. During the interview, the health states were labelled using symbols, as opposed to numerical identifiers, to avoid imposing any hierarchical order among them.

In total, 113 patients diagnosed with naïve CLL at Seoul St. Mary’s Hospital, Catholic University of Korea, from March 2018 to December 2021 were included in the study. Patients were diagnosed according to the World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues on the basis of their clinical features, laboratory findings (PB and/or BM morphology, and flow cytometric immunophenotyping), cytogenetics, and molecular genetics [1 (link)]. Morphologic characteristics of CLL were reviewed on PB smears and/or BM aspiration smears and hematoxylin and eosin-stained tissue sections and confirmed independently by two experienced hematopathologists to exclude other small B-cell lymphomas. CLL with atypical immunophenotype was regarded when either CD5 or CD23 were negative or dim positive (−/dim+), or when FMC7 is positive [60 ]. Extramedullary involvement and localization were assessed using positron emission tomography/computed tomography. Initial staging was performed according to the Rai and Binet systems [61 (link),62 (link)]. This study was approved by the institutional review board of Seoul St. Mary’s Hospital (KC21RISI0569).
Decision-making for treatment initiation was performed following the international workshop on CLL 2018 (iwCLL 2018) [63 (link)]. Most patients were monitored every 4–6 months without intervention because they did not exhibit any symptoms and signs of advanced disease or evidence of progressive disease (n = 73). The combination of fludarabine, cyclophosphamide, and rituximab (FCR) was the most commonly used treatment regimen (n = 22), followed by rituximab plus bendamustine (n = 6) and obinutuzumab plus chlorambucil (n = 5). Other regimens included acalabrutinib monotherapy (n = 4), acalabrutinib, venetoclax plus obinutuzumab (n = 1), venetoclax plus obinutuzumab (n = 1), and venetoclax plus acalabrutinib (n = 1).

The study population was retrospectively selected from a database of patients with FL, referred to our Institute between January 2011 and May 2019, with a post-treatment follow-up of at least 30 months. The sample included 79 patients with newly diagnosed FL grades 1–3A according to the 2016 WHO classification, treated with first-line chemotherapy regimens R-CHOP-like or R-B. Patients who relapsed within 30 months were also included in the analysis.
Patient inclusion criteria included an age range of 60–80 years, a baseline 18FDG PET/CT scan suitable for radiomic analysis performed at the Department of Diagnostic Imaging Radiology of the Policlinico Tor Vergata, first-line treatment with six cycles R-CHOP: Rituximab 375 mg/m², Cyclophosphamide 750 mg/m², Doxorubicin 50 mg/m² (liposomal Doxorubicin 50 mg/m² in R-COMP), Vincristine 1.4 mg/m²(for a maximum of 2 mg total dose) on day 1 and Prednisone 100 mg for 5 days every 21 days) or six cycles of R-B: Rituximab 375 mg/m² on day 1 and Bendamustine 90 mg/m² on days 1 and 2 of the cycle every 28 days.
In order to ensure the population was homogeneous, patients diagnosed with FL grade 3B, patients who had not undergone baseline or reassessment 18FDG PET/CT after immunochemotherapy at our Institute, and patients for whom it was impossible to access the images or examine the radiomic parameters considered were excluded. Table 1 summarizes the characteristics of the evaluated patients.
The database included 150 patients with FL in the 60–80 age range, and 71 were excluded because they did not fulfil the inclusion criteria. Early-stage patients who had performed only locoregional radiotherapy or for whom treatment criteria were not matched were excluded from our study. Patients who had performed immunochemotherapy treatments other than the R-CHOP or R-B regimen were also excluded.
For each patient, PET/CT was performed at the beginning of immunochemotherapy treatment and one month after its completion. For each patient, we considered descriptive parameters such as age and sex and clinical criteria such as the date of diagnosis, histology, Ann Arbor stage, performance status according to the ECOG scale, weight, and height; from these we calculated FLIPI, response to the end of therapy, the date of progression (if present), and the date of last contact or death. Finally, from the radiomic parameters we calculated and measured BMD, SMI, VAT, SAT, SMD, and SMA at onset and after chemoimmunotherapy treatment.