Quality of life with cemiplimab plus chemotherapy for first-line treatment of advanced non–small cell lung cancer: Patient-reported outcomes from phase 3 EMPOWER-Lung 3

Background

EMPOWER-Lung 3, a randomized 2:1 phase 3 trial, showed clinically meaningful and statistically significant overall survival improvement with cemiplimab plus platinum-doublet chemotherapy versus placebo plus chemotherapy for first-line treatment of advanced non–small cell lung cancer. This study evaluated patient-reported outcomes (PROs).

Methods

PROs were assessed at day 1 (baseline), the start of each treatment cycle (every 3 weeks) for the first six doses, and then at start of every three cycles, using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30) and Quality of Life-Lung Cancer Module (QLQ-LC13) questionnaires. Prespecified analyses included a longitudinal mixed-effect model comparing treatment arms and a time to definitive clinically meaningful deterioration (TTD) analysis performed for global health status/quality of life (GHS/QoL) and all scales from the questionnaires. Between-arm TTD comparisons were made using a stratified log-rank test and proportional hazards model.

Results

A total of 312 patients were assigned to receive cemiplimab plus platinum-doublet chemotherapy and 154 to receive placebo plus chemotherapy; 391 (83.9%) were male and the median age was 63.0 years (range, 25–84). For pain symptoms (EORTC QLQ-C30), a statistically significant overall improvement from baseline (−4.98, 95% confidence interval [CI] −8.36 to −1.60, p = .004) and a statistically significant delay in TTD (hazard ratio, 0.39; 95% CI, 0.26–0.60, p < .0001) favoring cemiplimab plus chemotherapy were observed. Statistically significant delays in TTD, all favoring cemiplimab plus chemotherapy, were also observed in functioning and symptom scales. A significant overall improvement from baseline in GHS/QoL was seen for cemiplimab plus chemotherapy compared with nonsignificant overall change from baseline for placebo plus chemotherapy (1.69, 95% CI, 0.20–3.19 vs. 1.08, 95% CI, –1.34 to 3.51; between arms, p = .673). No analyses yielded statistically significant PRO results favoring placebo plus chemotherapy for any QLQ-C30 or QLQ-LC13 scale.

Conclusion

Cemiplimab plus chemotherapy resulted in significant overall improvement in pain symptoms and delayed TTD in cancer-related and lung cancer–specific symptoms and functions.     

Efficacy of a global supportive skin care programme with hydrotherapy after non‐metastatic breast cancer treatment: A randomised,controlled study

This study investigated the efficacy of post‐treatment hydrotherapy as supportive care for management of persistent/long‐lasting dermatologic adverse events (dAEs) induced in breast cancer survivors by adjuvant therapy, and its impact on quality of life (QoL). Patients in complete remission after standardised (neo)adjuvant chemotherapy, surgery and radiotherapy combination treatment for infiltrating HR+/HER2‐breast carcinoma were enrolled in this randomised, multicentre controlled study 1–5 weeks after completing radiotherapy. The control group (CG, n = 33) received best supportive care and the treatment group (HG, n = 35) received 3‐weeks of specific hydrotherapy. The primary criterion was change in QoL (QLQ‐BR23) after hydrotherapy. Clinical grading of dAEs, cancer‐related QoL (QLQ‐C30), dermatologic QoL (DLQI) and general psychological well‐being (PGWBI) were assessed. Significant dAEs were found at inclusion in both groups (n = 261). Most items showed significantly greater improvement in the HG versus CG group: QLQ‐BR23 (breast [p = .0001] and arm symptoms [p = .0015], systemic therapy side effects [p = .0044], body image [p = .0139]), some dAE grading, DLQI (p = .0002) and PGWBI (p = .0028). Xerosis (88% of patients at inclusion) completely healed in all HG patients. Specific hydrotherapy is an effective supportive care for highly prevalent and long‐lasting dAEs occurring after early breast cancer treatment, including chemotherapy, and leads to improved QoL and dermatologic toxicities.     

The effect of cigarette smoking on cancer treatment-related side effects

Background.

Cigarette smoking has long been implicated in cancer development and survival. However, few studies have investigated the impact of smoking on symptom burden in cancer survivors during treatment and at survivorship stage. This study examines the influence of cigarette smoking on side effects among 947 cancer patients during and 6 months following treatment.

Methods.

Patients diagnosed with cancer and scheduled to receive chemotherapy and/or radiation therapy reported on current smoking status (yes, no) and total symptom burden [the sum of 12 common symptoms (fatigue, hair loss, memory, nausea, depression, sleep, pain, concentration, hot flashes, weight loss, skin problems, and dyspnea) scored on an 11-point scale ranging from 0 = “not present” to 10 = “as bad as you can imagine”] during treatment and at 6-month follow-up. The adjusted mean total symptom burden by smoking status was determined by analysis of covariance controlling for age, gender, race, education, occupation, treatment, cancer site, and Karnofsky performance score.

Results.

During treatment, smokers (S) had a significantly higher total symptom burden than nonsmokers (NS) (S = 46.3 vs. NS = 41.2; p < 0.05). At 6-month follow-up, smokers continued to report a higher total symptom burden than nonsmokers (S = 27.7 vs. NS = 21.9; p < 0.05). Participants who quit smoking before treatment levels had a total symptom burden similar to nonsmokers.

Conclusion.

Smoking was associated with an increased symptom burden during and following treatments for cancer. Targeted cessation efforts for smokers to decrease symptom burden may limit the likelihood of treatment interruptions and increase quality of life following treatment.     

The effect of cognitive behavioural therapy integrated with activity pacing on cancer-related fatigue,depression and quality of life among patients with breast cancer undergoing chemotherapy in Ethiopia: A randomised clinical trial

Fatigue is a common symptom experienced by 80% of individuals who receive chemotherapy and is one of the major factors that affect quality of life (QoL) of patients with breast cancer. Our study aimed to assess the effect of cognitive behavioural therapy integrated with activity pacing (CBT-AP) on cancer-related fatigue among patients with breast cancer undergoing chemotherapy. A parallel-group, randomised controlled trial was conducted. Severely fatigued patients were randomly assigned to the CBT-AP or usual care (UC) groups using a computer-generated random sequence. The new intervention was designed for seven sessions: three 2-hour face-to-face and four 30-minute telephone sessions. The primary outcome (fatigue severity) and the secondary outcomes (depression and QoL) were assessed at the end of the intervention and after 3 months. The data were analysed by repeated measures analyses of covariance (RM-ANCOVA). CBT-AP had a significant time effect (P < .001, ηp² = 0.233) in reducing fatigue from baseline (adjusted mean = 7.48) to the end of the intervention (adjusted mean = 6.37) and the 3-month follow-up (adjusted mean = 6.54). Compared to the UC group, the CBT-AP group had lower fatigue and depression scores, and higher global health status scores. The group × time interaction revealed a significant reduction in fatigue and depression in the CBT-AP group compared to the UC group. Therefore, CBT-AP appears to be effective in reducing fatigue and depression and improving QoL in patients with breast cancer undergoing chemotherapy. It is highly recommended to integrate a CBT-AP intervention in routine cancer care.     

MassBuilt: effectiveness of an apprenticeship site-based smoking cessation intervention for unionized building trades workers

Objective  Blue-collar workers are difficult to reach and less likely to successfully quit smoking. The objective of this study was to test a training site-based smoking cessation intervention. Methods  This study is a randomized-controlled trial of a smoking cessation intervention that integrated occupational health concerns and was delivered in collaboration with unions to apprentices at 10 sites (n = 1,213). We evaluated smoking cessation at 1 and 6 months post-intervention. Results  The baseline prevalence of smoking was 41%. We observed significantly higher quit rates in the intervention versus control group (26% vs. 16.8%; p = 0.014) 1 month after the intervention. However, the effects diminished over time so that the difference in quit rate was not significant at 6 month post-intervention (9% vs. 7.2%; p = 0.48). Intervention group members nevertheless reported a significant decrease in smoking intensity (OR = 3.13; 95% CI: 1.55–6.31) at 6 months post-intervention, compared to controls. Conclusion  The study demonstrates the feasibility of delivering an intervention through union apprentice programs. Furthermore, the notably better 1-month quit rate results among intervention members and the greater decrease in smoking intensity among intervention members who continued to smoke underscore the need to develop strategies to help reduce relapse among blue-collar workers who quit smoking.     

Circulating tumor DNA-based molecular residual disease detection for treatment monitoring in advanced melanoma patients

Background

Immune checkpoint inhibitors (ICIs) have substantially improved overall survival in patients with advanced melanoma; however, the lack of biomarkers to monitor treatment response and relapse remains an important clinical challenge. Thus, a reliable biomarker is needed that can risk-stratify patients for disease recurrence and predict response to treatment.

Methods

A retrospective analysis using a personalized, tumor-informed circulating tumor DNA (ctDNA) assay on prospectively collected plasma samples (n = 555) from 69 patients with advanced melanoma was performed. Patients were divided into three cohorts: cohort A (N = 30), stage III patients receiving adjuvant ICI/observation; cohort B (N = 29), unresectable stage III/IV patients receiving ICI therapy; and cohort C (N = 10), stage III/IV patients on surveillance after planned completion of ICI therapy for metastatic disease.

Results

In cohort A, compared to molecular residual disease (MRD)-negative patients, MRD-positivity was associated with significantly shorter distant metastasis-free survival (DMFS; hazard ratio [HR], 10.77; p = .01). Increasing ctDNA levels from the post-surgical or pre-treatment time point to after 6 weeks of ICI were predictive of shorter DMFS in cohort A (HR, 34.54; p < .0001) and shorter progression-free survival (PFS) in cohort B (HR, 22; p = .006). In cohort C, all ctDNA-negative patients remained progression-free for a median follow-up of 14.67 months, whereas ctDNA-positive patients experienced disease progression.

Conclusion

Personalized and tumor-informed longitudinal ctDNA monitoring is a valuable prognostic and predictive tool that may be used throughout the clinical course of patients with advanced melanoma.     

Effects and moderators of psychosocial interventions on quality of life,and emotional and social function in patients with cancer: An individual patient data meta‐analysis of 22 RCTs

Objective

This individual patient data (IPD) meta‐analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention‐related characteristics.

Methods

Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed‐effect model analyses were used to study intervention effects on the post‐intervention values of QoL, EF, and SF (z‐scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention‐related characteristics, and conducted subsequent stratified analyses for significant moderator variables.Results: PSI significantly improved QoL (β = 0.14,95%CI = 0.06;0.21), EF (β = 0.13,95%CI = 0.05;0.20), and SF (β = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types.

Conclusions

PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention‐related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients.

     

Epigenetic aging in older breast cancer survivors and noncancer controls: preliminary findings from the Thinking and Living with Cancer Study

Background

Cancer and its treatments may accelerate aging in survivors; however, research has not examined epigenetic markers of aging in longer term breast cancer survivors. This study examined whether older breast cancer survivors showed greater epigenetic aging than noncancer controls and whether epigenetic aging related to functional outcomes.

Methods

Nonmetastatic breast cancer survivors (n = 89) enrolled prior to systemic therapy and frequency-matched controls (n = 101) ages 62 to 84 years provided two blood samples to derive epigenetic aging measures (Horvath, Extrinsic Epigenetic Age [EEA], PhenoAge, GrimAge, Dunedin Pace of Aging) and completed cognitive (Functional Assessment of Cancer Therapy-Cognitive Function) and physical (Medical Outcomes Study Short Form-12) function assessments at approximately 24 to 36 and 60 months after enrollment. Mixed-effects models tested survivor-control differences in epigenetic aging, adjusting for age and comorbidities; models for functional outcomes also adjusted for racial group, site, and cognitive reserve.

Results

Survivors were 1.04 to 2.22 years biologically older than controls on Horvath, EEA, GrimAge, and DunedinPACE measures (p = .001–.04) at approximately 24 to 36 months after enrollment. Survivors exposed to chemotherapy were 1.97 to 2.71 years older (p = .001–.04), and among this group, an older EEA related to worse self-reported cognition (p = .047) relative to controls. An older epigenetic age related to worse physical function in all women (p < .001–.01). Survivors and controls showed similar epigenetic aging over time, but Black survivors showed accelerated aging over time relative to non-Hispanic White survivors.

Conclusion

Older breast cancer survivors, particularly those exposed to chemotherapy, showed greater epigenetic aging than controls that may relate to worse outcomes. If replicated, measurement of biological aging could complement geriatric assessments to guide cancer care for older women.     

Immune-Related Adverse Events as Clinical Biomarkers in Patients with Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors

Background

Immune checkpoint inhibitors (ICIs) are an important treatment for metastatic renal cell carcinoma (mRCC). These agents may cause immune-related adverse events (irAEs), and the relationship between irAEs and outcomes is poorly understood. We investigated the association between irAEs and clinical outcomes in patients with mRCC treated with ICIs.

Methods

We performed a retrospective study of 200 patients with mRCC treated with ICIs at Winship Cancer Institute from 2015 to 2020. Data on irAEs were collected from clinic notes and laboratory values and grades were determined using Common Terminology Criteria in Adverse Events version 5.0. The association with overall survival (OS) and progression-free survival (PFS) was modeled by Cox proportional hazards model. Logistic regression models were used to define odds ratios (ORs) for clinical benefit (CB). Landmark analysis and extended Cox models were used to mitigate lead-time bias by treating irAEs as a time-varying covariate.

Results

Most patients (71.0%) were male, and one-third of patients (33.0%) experienced at least one irAE, most commonly involving the endocrine glands (13.0%), gastrointestinal tract (10.5%), or skin (10.0%). Patients who experienced irAEs had significantly longer OS (hazard ratio [HR], 0.52; p = .013), higher chance of CB (OR, 2.10; p = .023) and showed a trend toward longer PFS (HR, 0.71; p = .065) in multivariate analysis. Patients who had endocrine irAEs, particularly thyroid irAEs, had significantly longer OS and PFS and higher chance of CB. In a 14-week landmark analysis, irAEs were significantly associated with prolonged OS (p = .045). Patients who experienced irAEs had significantly longer median OS (44.5 vs. 18.2 months, p = .005) and PFS (7.5 vs. 3.6 months, p = .003) without landmark compared with patients who did not.

Conclusion

We found that patients with mRCC treated with ICIs who experienced irAEs, particularly thyroid irAEs, had significantly improved clinical outcomes compared with patients who did not have irAEs. This suggests that irAEs may be effective clinical biomarkers in patients with mRCC treated with ICIs. Future prospective studies are warranted to validate these findings.

Implications for Practice

This study found that early onset immune-related adverse events (irAEs) are associated with significantly improved clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICIs). In this site-specific irAE analysis, endocrine irAEs, particularly thyroid irAEs, were significantly associated with improved clinical outcomes. These results have implications for practicing medical oncologists given the increasing use of ICIs for the treatment of mRCC. Importantly, these results suggest that early irAEs and thyroid irAEs at any time on treatment with ICIs may be clinical biomarkers of clinical outcomes in patients with mRCC treated with ICIs.

     

Discordance between clinical and pathologic staging and the timeliness of care of non-small cell lung cancer patients diagnosed with operable tumors

Aim

This study was performed to evaluate concordance between clinical and pathologic staging of non-small cell lung cancer (NSCLC) in our hospital network.

Methods

We retrospectively reviewed records of 417 patients with NSCLC who received curative surgery and whose pathology was evaluated in our hospital between 2016 and 2021. Cytology, tissue pathology, and associated clinical, surgical, and imaging information were retrieved from hospital digital records.

Results

The cohort included 214 female and 203 male patients aged 20.6–85.8 years. Median times among staging computed tomography and surgery (105 days [interquartile range (IQR) 77.0–143.0]), positron emission tomography and surgery (78.5 days [IQR 56.0–109.0]), and endobronchial ultrasound-guided transbronchial needle aspiration and surgery (59 days [IQR 42–94]) indicated that Australian guidelines of <42 days between original referral and commencement of treatment were not being met in the majority of cases. Discordance between clinical TNM (cTNM) and pathologic TNM staging was 25.9%, including 18.4% cases that were clinically understaged and two patients with undetected stage IVA disease. cTNM understaging was significantly associated with time between the final staging investigation and surgery (p = .023), pleural (p < .05) and vessel (p < .05) invasion, and diagnosis of high-grade adenocarcinoma (p = .001).

Conclusion

Discordance between clinical and pathologic staging of NSCLC is associated with tumor histopathologic characteristics and treatment delays. Although tumor factors that lead to discordant staging cannot be controlled, reduced time to surgery may have resulted in better outcomes for some patients in this potentially curable lung cancer cohort.     

Is a cancer diagnosis a teachable moment for the patient’s relative who smokes?

Purpose

This study examined a cancer diagnosis, versus orthopedic surgery, as a teachable moment for recruiting smokers and treating nicotine dependence among patients’ relatives.

Methods

Cancer patients and, for comparison, orthopedic patients at the University of Pennsylvania Health System were approached for referrals of relatives for a smoking cessation program, which involved behavioral counseling and nicotine patches. Primary outcomes were rate of program enrollment and rate of smoking abstinence. Potential mediators of smoking cessation were explored (e.g., treatment adherence, depression, anxiety). Two hundred and thirty-four relatives (113 cancer, 121 orthopedic) were considered eligible for the cessation program and comprised the study sample.

Results

Relatives of oncology patients were significantly more likely to enroll in the smoking cessation program, vs. orthopedic relatives (75 % vs. 60 %; OR = 1.96, 95 % CI 1.07–3.61, p = .03), but they were not significantly more likely to remain in the program (61 % vs. 52 %) or quit smoking (19 % vs. 26 %; p’s > .05). Compared to orthopedic relatives, oncology relatives showed significantly lower nicotine patch adherence and significantly greater levels of negative affect and depression and anxiety symptoms during treatment (p’s < .05). Further, orthopedic relatives, compared to oncology relatives, showed a greater reduction in the perceived benefits of smoking (p = .06), which was significantly associated with abstinence (p = .02).

Conclusions

While a family member’s cancer diagnosis may serve as a teachable moment for a smoker to enroll in a smoking cessation treatment program, high levels of psychological distress and perceptions of the benefits of smoking and low levels of treatment adherence may undermine successful abstinence among this population.     

Maximizing the extent of resection and survival benefit of patients in glioblastoma surgery: High-field iMRI versus conventional and 5-ALA-assisted surgery

Aims

A safe total resection followed by adjuvant chemoradiotherapy should be the primary goal in the treatment of glioblastomas (GBMs) to enable patients the longest survival possible. 5-aminolevulinic acid (5-ALA)- and intraoperative MRI (iMRI)-assisted surgery, have been shown in prospective randomized trials to significantly improve the extent of resection (EOR) and subsequently survival of patients with GBMs. No direct comparison of surgical results between both techniques has been published to date. We analyzed the additional value of iMRI in glioblastoma surgery compared to conventional surgery with and without 5-ALA.

Methods

Residual tumor volumes, clinical parameters and 6-month progression-free survival (6M-PFS) rates after GBM resection were analyzed retrospectively for 117 patients after conventional, 5-ALA and iMRI-assisted surgery.

Results

Mean residual tumor volume (range) after iMRI-assisted surgery [0.5 (0.0–4.7) cm³] was significantly smaller compared to the residual tumor volume after 5-ALA-guided surgery [1.9 (0.0–13.2) cm³; p = .022], which again was significantly smaller than in conventional white-light surgery [4.7 (0.0–30.6) cm³; p = .007]. Total resections were significantly more common in iMRI- (74%) than in 5-ALA-assisted (46%, p = .05) or white-light surgery (13%, p = .03). Improvement of the EOR by using iMRI was safely achievable as peri- and postoperative morbidities were comparable between cohorts. Total resections increased 6M-PFS from 32% to 45%.

Conclusions

Analysis of residual tumor volumes, total resections and neurological outcomes demonstrate that iMRI may be significantly superior to 5-ALA and white-light surgery for glioblastomas at comparable peri- and postoperative morbidities. Longer 6M-PFS was observed in patients with total resections.     

Health‐related quality of life associated with different cancer treatments in Chinese breast cancer survivors in Taiwan

We assessed the quality of life (QoL) associated with patient's characteristics and different cancer treatments among Chinese breast cancer survivors in Taiwan. A cross‐sectional survey was conducted in 2017 where 193 patients with hormone receptor‐positive/human epidermal growth factor receptor‐2‐negative metastatic breast cancer were recruited. Three QoL questionnaires were administered: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ‐C30), its breast cancer supplementary measure (QLQ‐BR23) and EQ‐5D‐5L. Multiple linear regression was performed to assess the association between QoL and cancer treatments, with adjustment for patient's characteristics. The mean age of study participants was 55.52 years. Simple linear regression showed that cancer stage and receiving chemotherapy were significantly associated with QoL scores (p < 0.05). Significant adverse effects of chemotherapy on QoL were found among early‐stage cancer women (i.e., I or II), including poor cognitive and sexual functioning, and a higher symptom burden (i.e., dyspnoea, constipation, systematic therapy side effects). Multiple linear regression also revealed that receiving chemotherapy was significantly associated with poor QoL (e.g., lower functional health and higher symptom burden measured by the QLQ‐BR23), compared to none chemotherapy (p < 0.05). Receiving chemotherapy was associated with poor QoL, especially among early‐stage breast cancer patients.     

Perceived importance of emotional support provided by health care professionals and social networks: Should we broaden our focus for the delivery of supportive care?

Introduction

Emotional support provided by health care professionals (HCPs) for people diagnosed with cancer is associated with improved outcomes. Support via social networks may also be important.

Aims

To report among a sample of distressed patients and caregivers, (1) the importance attributed to different sources of emotional support (HCPs and social networks) by distressed cancer patients and caregivers; (2) the proportion who indicate they did not receive sufficient levels of emotional support; and (3) potential associations between respondents’ demographic and clinical characteristics and reported lack of emotional support.

Methods

This study utilised cross-sectional data from telephone interviews collected during the usual-care phase of the Structured Triage and Referral by Telephone (START) trial. Participants completed a telephone interview 6 months after their initial call to the Cancer Council Information and Support service and included recall of importance and sufficiency of emotional support.

Results

More than two-thirds of patients (n = 234) and caregivers (n = 152) reported that family and friends were very important sources of emotional support. Nurses (69% and 42%) and doctors (68% and 47%) were reported very important, while a lower proportion reported that psychologists and psychiatrists were very important (39%, and 43%). Insufficient levels of support were reported by 36% of participants. Perceptions of insufficient support were significantly associated with distress levels (p < .0001) and not having a partner (p = .0115).

Conclusion

Social networks, particularly family, are an important source of emotional support. Higher levels of distress, those without partners, and caregivers may require targeted interventions to increase their access to emotional support.     

Quality of life after bone sarcoma surgery around the knee: A long‐term follow‐up study

It remains unclear if quality of life (QoL) improvements could be expected in young patients after malignant bone tumour surgery after 2 years. To assess the course of QoL over time during a long‐term follow‐up, malignant bone tumour survivors of a previous short‐term study were included. Assessments were done at least 5 years after surgery. QoL was measured with Short‐form (SF)‐36, TNO‐AZL Questionnaire for Adult's Quality of Life (TAAQOL) and Bone tumour (Bt)‐DUX. QoL throughout the follow‐up was analysed by linear mixed model analysis. From the original cohort of 44 patients; 20 patients were included for this study, 10 males; mean age at surgery 15.1 years and mean follow‐up 7.2 years. Twenty‐one patients of the initial cohort (47%) deceased. Fifteen patients (75%) underwent limb‐salvage and five (25%) ablative surgery. QoL improved significantly during follow‐up at Physical Component Summary Scale scale of the SF‐36 and TAAQOL and all subscales of the Bt‐DUX (p < .01). No significant differences were found between current evaluations and previous evaluations at 2 years after surgery (p = .41–.98). Significant advantages after limb‐salvage were seen at the PCS scale of the SF‐36 (MD 13.7, p = .05) and the cosmetic scale of the Bt‐DUX (MD 17.7, p = .04).     

Early intervention in myelofibrosis and impact on outcomes: A pooled analysis of the COMFORT-I and COMFORT-II studies

Background

In a pooled analysis of the phase 3 Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment I (COMFORT-I) and COMFORT-II clinical trials, adult patients with intermediate-2 or high-risk myelofibrosis who received oral ruxolitinib at randomization or after crossover from placebo or best available therapy (BAT) had improved overall survival (OS).

Methods

This post hoc analysis of pooled COMFORT data examined relevant disease outcomes based on the disease duration (≤12 or >12 months from diagnosis) before ruxolitinib initiation.

Results

The analysis included 525 patients (ruxolitinib: ≤12 months, n = 84; >12 months, n = 216; placebo/BAT: ≤12 months, n = 66; >12 months, n = 159); the median age was 65.0–70.0 years. Fewer thrombocytopenia and anemia events were observed among patients who initiated ruxolitinib treatment earlier. At Weeks 24 and 48, the spleen volume response (SVR) was higher for patients who initiated ruxolitinib earlier (47.6% vs. 32.9% at Week 24, p = .0610; 44.0% vs. 26.9% at Week 48, p = .0149). In a multivariable analysis of factors associated with spleen volume reduction, a logistic regression model that controlled for confounding factors found that a significantly greater binary reduction was observed among patients with shorter versus longer disease duration (p = .022). At Week 240, OS was significantly improved among patients who initiated ruxolitinib earlier (63% [95% CI, 51%‒73%] vs. 57% [95% CI, 49%‒64%]; hazard ratio, 1.53; 95% CI, 1.01‒2.31; p = .0430). Regardless of disease duration, a longer OS was observed for patients who received ruxolitinib versus those who received placebo/BAT.

Conclusions

These findings suggest that earlier ruxolitinib initiation for adult patients with intermediate-2 and high-risk myelofibrosis may improve clinical outcomes, including fewer cytopenia events, durable SVR, and prolonged OS.

Plain Language Summary

• Patients with myelofibrosis, a bone marrow cancer, often do not live as long as the general population. These patients may also have an enlarged spleen and difficult symptoms such as fatigue.
• Two large clinical trials showed that patients treated with the drug ruxolitinib lived longer and had improved symptoms compared to those treated with placebo or other standard treatments.
• Here it was examined whether starting treatment with ruxolitinib earlier (i.e., within a year of diagnosis) provided benefits versus delaying treatment.
• Patients who received ruxolitinib within a year of diagnosis lived longer and experienced fewer disease symptoms than those whose treatment was delayed.

     

Proton beam radiotherapy versus transarterial chemoembolization for hepatocellular carcinoma: Results of a randomized clinical trial

Background

This study compares survival rates, recurrence patterns, toxicity, and treatment cost in patients with hepatocellular carcinoma (HCC) treated with either transarterial chemoembolization (TACE) or proton beam radiotherapy (PBT).

Methods

Subjects with untreated HCC meeting Milan or San Francisco transplant criteria were recruited. Subjects were randomized to receive PBT (n = 36) or TACE (n = 40). Proton therapy was administered in 15 fractions over 3 weeks to a total dose of 70.2 Gy. TACE was repeated until complete or maximal response. The primary outcome measure was overall survival (OS). Secondary end points were progression-free survival (PFS), local control (LC), toxicity, and cost.

Results

Of the 76 randomized patients, 74 were assessed for outcome measures. The 2-year OS for PBT versus TACE was similar at 68%, 95% confidence interval (CI), 0.54–0.86, and 65%, 95% CI, 0.52–0.83 (p = .80), however, median PFS was improved for PBT versus TACE (not reached vs. 12 months, p = .002). LC was improved with PBT versus TACE (hazard ratio, 5.64; 95% CI, 1.78–17.9, p = .003). Days of posttreatment hospitalization were 24 for PBT and 166 for TACE (p < .001). Total mean cost per patient for treatment and posttreatment care revealed a 28% cost savings for PBT.

Conclusions

PBT and TACE yielded similar OS for treatment of HCC, but PFS and LC were improved with PBT compared to TACE. Patients treated with PBT required fewer courses of treatment, fewer posttreatment hospitalization days, and reduced cost of treatment compared to TACE. These data support the use of PBT as a viable treatment alternative to TACE for patients with HCC within transplant criteria.     

Parents’ and adolescents’ perspectives and understanding of information about childhood cancer precision medicine

Background

Precision medicine is projected to become integral to childhood cancer care. As such, it is essential to support families to understand what precision medicine entails.

Methods

A total of 182 parents and 23 adolescent patients participating in Precision Medicine for Children with Cancer (PRISM), an Australian precision medicine clinical trial for high-risk childhood cancer, completed questionnaires after study enrollment (time 0 [T0]). Of the parents, 108 completed a questionnaire and 45 completed an interview following return of precision medicine results (time 1 [T1]). We analyzed the mixed-methods data comprising measures exploring families’ perceptions and understanding of PRISM’s participant information sheet and consent form (PISCF), and factors associated with understanding.

Results

Most parents were satisfied with the PISCF, rating it as at least “somewhat” clearly presented (n = 160/175; 91%) and informative (n = 158/175; 90%). Many suggested improvements including the use of clearer language and a more visually engaging format. Parents’ actual understanding of precision medicine was low on average, but scores improved between T0 and T1 (55.8/100-60.0/100; p = .012). Parents from culturally and/or linguistically diverse backgrounds (n = 42/177; 25%) had lower actual understanding scores than those from a Western/European background whose first language was English (p = .010). There was little correlation between parents’ perceived and actual understanding scores (p = .794; Pearson correlation –0.020; 95% CI, –0.169 to 0.116). Most adolescent patients read the PISCF either “briefly” or “not at all” (70%) and had a perceived understanding score of 63.6/100 on average.

Conclusions

Our study revealed gaps in families’ understanding of childhood cancer precision medicine. We highlighted areas for potential intervention such as through targeted information resources.

Plain Language Summary

• Precision medicine is projected to become part of the standard of care for children with cancer. Precision medicine aims to give the right treatment to the right patient and involves several complex techniques, many of which may be challenging to understand.
• Our study analyzed questionnaire and interview data from parents and adolescent patients enrolled in an Australian precision medicine trial.
• Findings revealed gaps in families’ understanding of childhood cancer precision medicine. Drawing on parents’ suggestions and the literature, we make brief recommendations about improving information provision to families, such as through targeted information resources.

     

Dramatic dietary fat reduction is feasible for breast cancer patients: Results of the randomised study, WINS (UK) – Stage 1

Introduction

The influence of dietary fat on breast tumour growth¹ and, more recently, on treatment outcomes, ^{[2] and [3]} suggests an important role for dietary advice in the future health of breast cancer patients. The Women’s Intervention Nutrition Study (UK) – Stage 1 assessed the feasibility of achieving and maintaining a ≥50% reduction in reported fat intake in postmenopausal, early stage breast cancer patients in the UK.

Method

This study recruited patients in South-east England between 2000 and 2005. They were randomly allocated into two groups. Group 1 (n = 54), received specific dietary counselling to halve their reported fat intake and maintain this low fat intake. Group 2 (n = 53) received healthy eating advice only. Dietitian-led group sessions provided support for women in both groups over 2 years.⁴ Validated four-day diaries were used to measure intake. Data analysis used Generalised Linear Model (GLM) for repeated measures and logistic regression.

Results

A significantly greater proportion of women in Group 1 reported a fat intake reduction of ≥50% at 3 months (p < .001) and 24 months (p < .001) than in Group 2. The size of the effect of active dietary counselling was 37% at 3 months (95%CI: 21–54%) and 35% at 24 months (95%CI: 17–53%). Mean fat intake was halved at 3 months and 24 months in Group 1 only.

Conclusion

Demonstrating such feasibility is a key step towards defining diet’s role in the secondary prevention of breast cancer.     

The Impact of Baseline Edmonton Symptom Assessment Scale Scores on Treatment and Survival in Patients With Advanced Non–small-cell Lung Cancer

Background

Palliative systemic therapy is frequently underutilized in patients with advanced non–small-cell lung cancer (NSCLC), for many reasons. The aim of this study was to identify patient-reported factors that may predict for treatment decisions and survival in advanced NSCLC, using the Edmonton Symptom Assessment Scale (ESAS), which is a self-reported questionnaire that quantifies symptom burden by asking patients to rate the severity of 9 common symptoms.