Utility of molecular markers in predicting local control specific to lung cancer spine metastases treated with stereotactic body radiotherapy.

BACKGROUND AND PURPOSE: We report outcomes following spine stereotactic body radiotherapy (SBRT) in metastatic non-small cell lung cancer (NSCLC) and the significance of programmed death-ligand 1 (PD-L1) status, epidermal growth factor receptor (EGFR) mutation and timing of immune check point inhibitors (ICI) on local failure (LF). MATERIALS AND METHODS: 165 patients and 389 spinal segments were retrospectively reviewed from 2009 to 2021. Baseline patient characteristics, treatment and outcomes were abstracted. Primary endpoint was LF and secondary, overall survival (OS) and vertebral compression fracture (VCF). Multivariable analysis (MVA) evaluated factors predictive of LF and VCF. RESULTS: The median follow-up and OS were: 13.0 months (range, 0.5-95.3 months) and 18.4 months (95% CI 11.4-24.6). 52.1% were male and 76.4% had adenocarcinoma. Of the 389 segments, 30.3% harboured an EGFR mutation and 17.0% were PD-L1 ≥ 50%. The 24 months LF rate in PD-L1 ≥ 50% vs PD-L1 < 50% was 10.7% vs. 38.0%, and in EGFR-positive vs. negative was 18.1% vs. 30.0%. On MVA, PD-L1 status of ≥ 50% (HR 0.32, 95% CI 0.15-0.69, p = 0.004) significantly predicted for lower LF compared to PD-L1 < 50%. Lower LF trend was seen with ICI administration peri and post SBRT (HR 0.41, 95% CI 0.16-1.05, p = 0.062). On MVA, polymetastatic disease (HR 3.28, 95% CI 1.84-5.85, p < 0.0001) and ECOG ≥ 2 (HR 1.87, 95% CI 1.16-3.02, p = 0.011) significantly predicted for worse OS and absence of baseline VCF predicted for lower VCF rate (HR 0.20, 95% CI 0.10-0.39, p < 0.0001). CONCLUSION: We report a significant association of PD-L1 ≥ 50% status on improved LC rates from spine SBRT in NSCLC patients.

Enhancing Nutrition Support for Esophageal Cancer Patients: Understanding Factors Influencing Feeding Tube Utilization.

Objective: We sought to identify factors that can predict esophageal cancer (EC) patients at high risk of requiring feeding tube insertion. Methods: A retrospective cohort review was conducted, including all patients diagnosed with EC at our cancer center from 2013 to 2018. Multivariate logistic regression was performed comparing the group that required a reactive feeding tube insertion to those who did not require any feeding tube insertion to identify risk factors. Results: A total of 350 patients were included in the study, and 132/350 (38%) patients received a feeding tube. 50 out of 132 (38%) patients had feeding tube inserted reactively. Severe dysphagia (OR 19.9, p < 0.001) at diagnosis and decision to undergo chemotherapy (OR 2.8, p = 0.008) appeared to be predictors for reactive feeding tube insertion. The reactive insertion group had a 7% higher rate of complications relating to feeding tube. Conclusion: Severe dysphagia at diagnosis and undergoing chemotherapy were identified as risk factors for requiring a feeding tube. Ultimately, the aim is to create a predictive tool that utilizes these risks factors to accurate identify high-risk patients who may benefit from prophylactic feeding tube insertion.

Bridging research gaps in geriatric oncology: unraveling the potential of pragmatic clinical trials.

PURPOSE OF REVIEW: This review examines the role of pragmatic clinical trials (PCTs) in addressing the underrepresentation of older adults with cancer (OAC) in clinical trials. Focusing on real-world evidence (RWE), it aims to provide a comprehensive overview of PCT utilization, emphasizing their potential to enhance treatment decisions and patient outcomes. Existing knowledge gaps in PCT implementation are also discussed. RECENT FINDINGS: PCTs are identified as effective tools to include OACs with comorbidities and complex conditions in research, bridging the representation gap. Despite their proven value in healthcare provision, their application in OAC contexts remains limited, hindering comprehensive understanding and inclusivity in clinical trials. SUMMARY: While randomized controlled trials (RCTs) are considered the gold standard in oncology research, OACs have historically been excluded, perpetuating underrepresentation. Furthermore, even in current oncology clinical development trials, this demographic continues to be underrepresented. PCTs offer a valuable avenue for the identification and evaluation of therapies within authentic RW contexts, encompassing various healthcare settings, such as hospitals, clinics, and physician practices. RCTs and PCTs complement one another, and the utilization of PCTs has the potential to inform clinical decision-making across the OACs entire treatment trajectory.

Implementing geriatric assessment and management for older Canadians with cancer: Adherence to and satisfaction with the intervention, results of the 5C study.

INTRODUCTION: Geriatric assessment and management (GAM) is recommended by professional organizations and recently several randomized controlled trials (RCTs) demonstrated benefits in multiple health outcomes. GAM typically leads to one or more recommendations for the older adult on how to optimize their health. However, little is known about how well recommendations are adhered to. Understanding these issues is vital to designing GAM trials and clinical programs. Therefore, the aim of this study was to examine the number of GAM recommendations made and adherence to and satisfaction with the intervention in a multicentre RCT of GAM for older adults with cancer. MATERIALS AND METHODS: The 5C study was a two-group parallel RCT conducted in eight hospitals across Canada. Each centre kept a detailed recruitment and retention log. The intervention teams documented adherence to their recommendations. Medical records were also reviewed to assess which recommendations were adhered to. Twenty-three semi-structured interviews were conducted with 12 members of the intervention teams and 11 oncology team members to assess implementation of the study and the intervention. RESULTS: Of the 350 participants who were enrolled, 173 were randomized to the intervention arm. Median number of recommendations was seven. Mean adherence to recommendations based on the GAM was 69%, but it varied by type of recommendation, ranging from 98% for laboratory tests to 28% for psychosocial/psychiatry oncology referrals. There was no difference in the number of recommendations or non-adherence to recommendations by sex, level of frailty, or functional status. Oncologists and intervention team members were satisfied with the study implementation and intervention delivery. DISCUSSION: Adherence to recommendations was variable. Adherence to laboratory investigations and further imaging were generally high but much lower for recommendations regarding psychosocial support. Further collaborative work with older adults with cancer is needed to understand how to optimize the intervention to be consistent with patient goals, priorities, and values to ensure maximal impact on health outcomes.

Cost-effectiveness of second-line ipilimumab for metastatic melanoma: A real-world population-based cohort study of resource utilization.

BACKGROUND: The efficacy-effectiveness gap between randomized trial and real-world evidence regarding the clinical benefit of ipilimumab for metastatic melanoma (MM) has been well characterized by previous literature, consistent with initial concerns raised by health technology assessment agencies (HTAs). As these differences can significantly impact cost-effectiveness, it is critical to assess the real-world cost-effectiveness of second-line ipilimumab versus non-ipilimumab treatments for MM. METHODS: This was a population-based retrospective cohort study of patients who received second-line non-ipilimumab therapies between 2008 and 2012 versus ipilimumab treatment between 2012 and 2015 (after public reimbursement) for MM in Ontario. Using a 5-year time horizon, censor-adjusted and discounted (1.5%) costs (from the public payer's perspective in Canadian dollars) and effectiveness were used to calculate incremental cost-effectiveness ratios (ICERs) in life-years gained (LYGs) and quality-adjusted life years (QALYs), with bootstrapping to capture uncertainty. Varying the discount rate and reducing the price of ipilimumab were done as sensitivity analyses. RESULTS: In total, 329 MM were identified (Treated: 189; Controls: 140). Ipilimumab was associated with an incremental effectiveness of 0.59 LYG, incremental cost of $91,233, and ICER of $153,778/LYG. ICERs were not sensitive to discounting rate. Adjusting for quality of life using utility weights resulted in an ICER of $225,885/QALY, confirming the original HTA estimate prior to public reimbursement. Reducing the price of ipilimumab by 100% resulted in an ICER of $111,728/QALY. CONCLUSION: Despite its clinical benefit, ipilimumab as second-line monotherapy for MM patients is not cost-effective in the real world as projected by HTA under conventional willingness-to-pay thresholds.

Immunotherapy for older patients with cancer.

PURPOSE OF THE REVIEW: The aim of this review is to describe the clinical use and tolerability of immune checkpoint inhibitors in older adults with solid tumors, where there is an abundance of evidence with recent updates including subgroups of older patients. RECENT FINDINGS: Studies with updated analyses and subgroups of older patients show that in general older patients benefit as well as younger patients and tolerate immunotherapy very well. However, in some instances of combination therapies which may expose patients to more toxicity, the benefits are reduced, and careful selection of older patients, including adjunctive assessments such as geriatric assessment, can help to identify the appropriate treatment for an individual patient. SUMMARY: Older adults remain underrepresented in clinical trials, including those involving immunotherapy. Therefore, efforts must be made to include more older patients in trials and to assess real-world evidence to inform decision-making.

Impact of Geriatric Assessment and Management on Quality of Life, Unplanned Hospitalizations, Toxicity, and Survival for Older Adults With Cancer: The Randomized 5C Trial.

PURPOSE: American Society of Clinical Oncology recommends that older adults with cancer being considered for chemotherapy receive geriatric assessment (GA) and management (GAM), but few randomized controlled trials have examined its impact on quality of life (QOL). PATIENTS AND METHODS: The 5C study was a two-group parallel 1:1 single-blind multicenter randomized controlled trial of GAM for 6 months versus usual oncologic care. Eligible patients were age 70+ years, diagnosed with a solid tumor, lymphoma, or myeloma, referred for first-/second-line chemotherapy or immunotherapy or targeted therapy, and had an Eastern Cooperative Oncology Group performance status of 0-2. The primary outcome QOL was measured with the global health scale of the European Organisation for the Research and Treatment of Cancer QOL questionnaire and analyzed with a pattern mixture model using an intent-to-treat approach (at 6 and 12 months). Secondary outcomes included functional status, grade 3-5 treatment toxicity; health care use; satisfaction; cancer treatment plan modification; and overall survival. RESULTS: From March 2018 to March 2020, 350 participants were enrolled. Mean age was 76 years and 40.3% were female. Fifty-four percent started treatment with palliative intent. Eighty-one (23.1%) patients died. GAM did not improve QOL (global QOL of 4.4 points [95% CI, 0.9 to 8.0] favoring the control arm). There was also no difference in survival, change in treatment plan, unplanned hospitalization/emergency department visits, and treatment toxicity between groups. CONCLUSION: GAM did not improve QOL. Most intervention group participants received GA on or after treatment initiation per patient request. Considering recent completed trials, GA may have benefit if completed before treatment selection. The COVID-19 pandemic may have affected our QOL outcome and intervention delivery for some participants.

The development of an electronic geriatric assessment tool: Comprehensive health assessment for my plan (CHAMP).

INTRODUCTION: Geriatric assessment (GA) provides information on key health domains of older adults and is recommended to help inform cancer treatment decisions and cancer care. However, GA is not feasible in many health institutions due to lack of geriatric staff and/or resources. To increase accessibility to GA and improve treatment decision making for older adults with cancer (≥65 years), we developed a self-reported, electronic geriatric assessment tool: Comprehensive Assessment for My Plan (CHAMP). MATERIALS AND METHODS: Older adults with cancer were invited to join user-centered design sessions to develop the layout and content of the tool. Subsequently, they participated in usability testing to test the usability of the tool (ease of use, acceptability, etc.). Design sessions were also conducted with oncology clinicians (oncologists and nurses) to develop the tool's clinician interface. GA assessment questions and GA recommendations were guided by a systematic review and Delphi expert panel. RESULTS: A total of seventeen older adults participated in the study. Participants were mainly males (82.4%) and 75% were aged 75 years and older. Nine oncology clinicians participated in design sessions. Older adults and clinicians agreed that the tool was user-friendly. Domains in the final CHAMP tool (with questions and recommendations) included functional status, falls risk, cognitive impairment, nutrition, medication review, social supports, depression, substance use disorder, and miscellaneous items. DISCUSSION: CHAMP was designed for use by older adults and oncologists and may enhance access to GA for older adults with cancer. The next phase of the CHAMP study will involve field validation in oncology clinics.

The effect of age on the opportunity to receive cancer treatment.

INTRODUCTION: Older adults with cancer may not receive the same opportunities for treatment as younger patients. In this retrospective population-based cohort study, we explored whether age was an independent predictor of receiving specialist consultation and treatment. METHODS: Patients age 45-99 were identified from the Ontario Cancer Registry having a primary solid tumor diagnosed between 01/Jan/2010 and 31/Dec/2019. We used logistic regression adjusted sociodemographic and clinical characteristics to compare the likelihood of consultation or receipt of treatment using linear splines at critical ages of 65, 80, and 90 years. RESULTS: A total 168,232 (42%), 165,205 (41%), 57,360 (14%), and 7810 (2%) patients were diagnosed age 45-64, 65-79, 80-89, and 90-99, respectively. The likelihood of surgical consultation decreased as patients reached 65 years [adjusted odds ratio (aOR) 0.86 (0.84-0.89)], which decreased further among octogenarians [aOR 0.63 (0.59-0.67)]. Similar results were observed for consultation with a medical oncologist and radiation oncologist. Receipt of surgery also decreased with age. Three-month post-operative mortality was higher among older patients [aRR 1.38 (1.26-1.50) per 10 years, p < 0.0001], an effect that remained similar as patients reached age 65 + years of age (p = 0.09 for change). For stage I patients, 3-month post-operative survival was high across all age groups, ranging from 99.8% in 45-64 year-olds, 99.4% in 65-79 year-olds, and 98.1% among octogenarians and nonagenarians (lung, colorectal, breast, cervical cancer patients). CONCLUSION: Older patients were less likely to have specialist consultations. More comprehensive data collection on clinical factors and referral patterns is needed to improve care for elderly cancer patients.

Impact of body mass index on survival in women receiving chemotherapy for early breast cancer.

PURPOSE: The impact of elevated body mass index (BMI) on overall survival (OS) in patients receiving modern anthracycline-taxane chemotherapy for early breast cancer (EBC) has not yet been well established. The purpose of our study was to examine overall survival (OS) by BMI category in women with EBC receiving either doxorubicin (A), cyclophosphamide (C) + paclitaxel (P) or fluorouracil (F), epirubicin (E), cyclophosphamide (C) + docetaxel (D). METHODS: This was a retrospective cohort study in patients ≥ 18 years with resected stage I-III BC diagnosed between 2007 and 2017 in Ontario, identified through linkage of administrative databases. Patients were classified according to baseline BMI into underweight (< 18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (≥ 30 kg/m2) World Health Organization (WHO) categories. The primary outcome was OS. Univariable and multivariable analyses were used to examine the association between clinico-pathologic characteristics and OS among BMI categories. RESULTS: Our cohort included 11,601 women, of whom 3890 (33.5%) were normal weight, 3696 (31.9%) overweight, and 3847 (33.1%) obese. Median OS was 7.9 years. There were no statistically significant differences in OS according to BMI (p = 0.66) in the overall study cohort or among the BMI categories after adjusting for age, nodal status, stage, grade, ER and HER2 status for either AC-P or FEC-D- treated patients (p = 0.45 and p = 0.97, respectively). CONCLUSIONS: Our large population-based retrospective cohort analysis of EBC patients receiving adjuvant anthracycline-taxane chemotherapy found no significant impact of BMI on OS. Further investigation is warranted to confirm these findings in prospective patient cohorts.

Retrospective analysis of VES-13 questionnaires in the Senior Women's Breast Cancer Clinic at Sunnybrook Health Sciences, Toronto, Ontario, Canada.

PURPOSE: Vulnerable Elder Survey (VES-13) is a screening tool used in assessing older vulnerable patients at risk of functional decline. We sought to evaluate how VES-13 tool would impact oncologist referral pattern to geriatricians as our primary outcome. We also sought to better understand how VES-13 scores impacted referral to additional services (allied healthcare), and modification to oncological treatment. METHODS: A retrospective review of VES-13 questionnaires completed by older women (age 70 or older) with breast cancer referred to the Senior Women's Breast Cancer Clinic (SWBCC) was undertaken. Patients with a VES-13 score of three or greater, who were at significantly higher risk of functional decline, had further retrospective chart review for risk factors that would contribute to functional decline such as Eastern Cooperative Oncology Group (ECOG) score, social supports, and current living situation. The primary and secondary endpoints described above were analyzed through bivariate comparisons and multivariable logistical regression to determine if there was any statistical significance (p < 0.05). RESULTS: 701 patients completed VES-13 form, of which 235 (33.5%) had a VES-13 score of three or greater. Less than 5% of oncologists documented VES-13 scores in their notes, with less than 5% of patients being referred for geriatric services. Neither VES-13 (p= 0.900) nor ECOG (p= 0.424) were associated with referral for geriatrics assessment. Referral to allied healthcare services was significantly associated with (ECOG) score (OR 2.24 [1.49-3.37], p < 0.0001), while not significantly associated with VES-13 score (OR 0.89 [0.78-1.02], p= 0.102). VES-13 (OR 1.23 [1.04-1.45], p=0.014) and ECOG (OR 2.37 [1.29-4.37), p=0.005) were both associated with modification in oncology treatment (chemotherapy or radiation). CONCLUSION: Approximately one third of our population was at risk of functional decline. VES-13 scores were infrequently mentioned in oncologists notes from their clinical assessments, with very few patients being referred for geriatric assessment. By not collecting and analyzing VES-13 scores, and relying on performance status alone, there is a missed opportunity in assessing for functional decline and reducing potential complications from treatment for our patients.

Evaluation of a Multidisciplinary Immunotherapy Toxicity Monitoring Program for Patients Receiving Ipilimumab for Metastatic Melanoma.

PURPOSE: Ipilimumab is an effective treatment for melanoma; however, toxicity rates remain high. The objective of this study was to describe the rates of adverse events (AEs), emergency room (ER) visits, hospitalizations, and nursing resource utilization for patients enrolled in a nurse-led telephone toxicity monitoring program. METHODS: Patients received weekly telephone calls from nursing to review a toxicity checklist during ipilimumab treatment and for 8 weeks after completion. To evaluate this program, a single-center retrospective review was performed for patients treated between July 2012 and September 2017 with single agent ipilimumab for advanced melanoma. Data were collected up to 3 months post-ipilimumab. RESULTS: A total of 67 patients were included, with a mean (standard deviation) age of 61 (14.6) years. Thirty-three (49%) patients received four doses of ipilimumab, and 17 (25%) had one dose delay. The median (IQR) of any AEs reported per patient was 11 (8-17). There were 44 (66%) patients with AEs deemed to be definitely or probably related to ipilimumab, and of those, 3 (4%) experienced a grade 3 AE, whereas 4 (6%) experienced grade 4 AEs. Twenty patients (30%) had ER visits, and 31 (46%) were hospitalized during follow-up (9% ER visits and 6% hospitalizations were related to drug toxicity). CONCLUSION: Ipilimumab is associated with high rates of toxicity; however, a proactive nurse-led monitoring program was feasible and patients had low rates of grade 3-4 toxicity. Hospitalization rates and ER visits remained high; however, the minority of those were related to drug toxicity.

Predicting treatment toxicity in older adults with cancer.

PURPOSE OF REVIEW: To provide an overview of the recent advancements in predicting toxicity associated with cancer treatment in older patients. RECENT FINDINGS: Various screening tools and validated risk calculators have been shown to help predict toxicity from surgery and chemotherapy. Radiation therapy has been more challenging to select the appropriate tool to reliably predict patients at risk for toxicity and noncompliance. Ongoing work on electronic geriatric assessment tools is showing promise in making comprehensive assessment more feasible. SUMMARY: Selecting appropriate cancer therapy is particularly important in older patients, and validated tools have been developed to guide clinicians for surgery and chemotherapy; however, radiotherapy toxicity remains an area for further development, as does the uptake of existing tools into routine oncology practice.

Real-world, population-based cohort study of toxicity and resource utilization of second-line ipilimumab for metastatic melanoma in Ontario, Canada.

Second-line ipilimumab has been publicly funded in Ontario for metastatic melanoma (MM) since September 2012. We examined real-world toxicity of second-line ipilimumab compared to standard second-line treatments prior to funding. MM patients who received systemic treatment from April 2005 to March 2015 were included. Patients receiving second-line ipilimumab after September 2012 were considered as cases, and those who received second-line treatment prior to the funding date were included as historical controls. Outcomes assessed include treatment-related mortality, any-cause hospital visits, ipilimumab-related hospital visits and specialist visits (eg, endocrinologists, ophthalmologists, gastroenterologists, rheumatologists and respirologists), which were captured from up to 30 and/or 90 days after end of second-line treatment. Inverse probability of treatment weighting was used to adjust for baseline differences between groups. Odds ratios (ORs) from logistic regressions and rate ratios (RRs) from rate regressions were used to assess differences between groups. We identified 329 MM patients who received second-line treatments (ipilimumab: 189; controls: 140). Ipilimumab was associated greater any-cause (60.1% vs 45.7%; OR = 1.81; P value = .019) and ipilimumab-related (47.2% vs 31.9%; OR = 1.91; P value = .011) hospital visits. Adjusting for different follow-up days, ipilimumab was associated with higher rates of all-cause (RR = 1.56 [95%CI: 1.12-2.16]), and ipilimumab-related (RR = 2.18 [95% CI: 1.45-3.27]) hospital visits. Patients receiving ipilimumab were more likely to visit specialist involved in immunotherapy toxicity management (23.5% vs 13.7%; P value = .04). Compared to historical second-line treatments, second-line ipilimumab was associated with more health service utilization (specifically hospital visits and specialist visits), suggestive of potentially increased toxicity in the real world.