Decline In Performance Status Research Articles

Combination anlotinib and toripalimab for an advanced biliary tract cancer patient with high Eastern Cooperative Oncology Group performance status: a case report.

Up to 80% of biliary tract cancer (BTC) patients relapse within 3 years after surgery and the efficacy of second-line treatment remains dismal for patients who progressed on gemcitabine and cisplatin chemotherapy. Median overall survival of patients with palliative chemotherapy is less than 1 year. The feasibility and safety of targeted therapies plus immunotherapies remain scanty currently, and patients with recurrent or advanced BTCs often experience a rapid decline in Eastern Cooperative Oncology Group (ECOG) performance status. This case report is the first report suggesting a 17-month progression-free survival (PFS), partial response, and another 11-month PFS after progressive disease of anlotinib plus toripalimab in advanced BTC with high ECOG performance status. We report a 67-year-old Chinese male with BTC. He was observed with progressive disease after surgical resection, adjuvant chemotherapy, palliative chemotherapy, and diagnosed with American Joint Committee on Cancer clinical stage IV (cT3N0M1) extrahepatic BTC. The patient experienced a rapid decline in performance status, and he received oral anlotinib and toripalimab with informed consent. MRI scans showed partial response on 22 June 2022. PET-CT showed that tumor activity has been inhibited on 8 March 2023. He achieved 17 months of PFS. Although the patient developed solitary lung metastasis, he had a continuous survival benefit from treatment of anlotinib plus toripalimab after lung radiotherapy. Until the writing of the case draft, he had achieved another 11 months of PFS. The present case suggests that anlotinib plus toripalimab might be a potential effective treatment for advanced BTCs patients with high ECOG performance status.

Neoadjuvant chemotherapy vs upfront resection: A challenging choice in resectable pancreatic ductal adenocarcinoma.

620 Background: Pancreatic ductal adenocarcinoma (PDAC) remains an immense challenge within oncology, with only 15-20% of cases initially qualifying as resectable. Based on National Cancer Database analyses there is an increase in neoadjuvant chemotherapy (NACT) use, with potential downstaging effects. Yet, a subset of neoadjuvant-treated patients fail to proceed with curative-intent surgery, leading to worse outcomes. This retrospective analysis aims to uncover factors that predict NACT use and the impact on survival outcomes. Methods: A cohort of 543 consecutive non-metastatic PDAC patients treated at an NCCN-designated comprehensive cancer center between 2015 and 2022 were prospectively enrolled into a REDCap database. Based on NCCN resectability criteria, initial CT staging placed 96 patients as upfront resectable. Survival outcomes were compared using univariate and multivariate cox regression analyses. Results: Within 96 resectable patients, 45 (47%) underwent upfront surgery, 36 (37%) received NACT followed by surgery and 15 (16%) only received chemotherapy. The majority were CA19-9 secretors (94%) with 54% lower values during chemotherapy. While 60% of patients experienced up to 35% tumor size reductions on NACT, 20% had stable disease, and 20% showed progressive disease. The patients who received NACT were significantly younger (p = 0.01), with higher baseline CA19-9 (p < 0.01) and more frequently underwent stent placement (p = 0.01), table 1. Median overall survival for the upfront surgery, NACT+surgery and chemotherapy groups were 32.8, 23.7 and 20.2 months (log-rank test p<0.01) subsequently. On univariate analysis initial presentation with weight loss (p = 0.02, HR = 2.08) and high baseline CA19-9 (log2-scaled, p = 0.01, HR = 1.13) were predictive of worse overall survival. After adjusting for potential confounding variables, patients in chemotherapy group had significantly worse survival compared to the upfront surgery group (P < 0.01, HR = 3.14). These 15 patients failed to undergo surgery due to diverse reasons, including distant progression (7), local progression (3), performance status decline or death during chemotherapy (2), refusal due to chemotherapy side effects (2), and indecision and loss to follow-up (1). Conclusions: These findings underscore the need for more robust selection criteria in resectable PDAC patients to undergo NACT. Leveraging real-world data helps identify predictive factors of treatment decision making and their impact on patient survival outcomes. [Table: see text]

Abstract C050: Comprehensive analysis of causes for unsuccessful genomic profiling in a Phase 1 setting

Abstract Purpose: Genomic profiling (GP) has revolutionized personalized cancer therapy, enabling tailored treatment strategies based on individual tumor characteristics. However, despite its widespread use, there are instances where GP fails. Understanding the causes of such failures is important for improving the success rate of GP. Here, we present a comprehensive analysis of unsuccessful GP within a phase 1 clinical setting. Materials and Methods: A prospective, single-center, single-arm open label study (NCT02290522) was conducted, enrolling patients with advanced cancer referred to a phase I unit. Fresh tumor tissue was obtained by core needle biopsy for whole genome- or whole exome sequencing and RNA sequencing. In cases where fresh tumor tissue was unavailable, archival, formalin-fixed, paraffin-embedded tumor tissue or circulating tumor DNA extracted from plasma were obtained. Results: Between March 2013 and December 2021, a total of 2151 patients with advanced cancers and exhausted or almost exhausted treatments options were enrolled in the study. GP was unsuccessful in 281 patients (13%). The reasons for failure were; abstaining from biopsy due to performance decline from the time of consent (115/281= 41%), inadequate tissue quality due to normal tissue or necrosis (52/281= 19%), absence of lesions for tissue biopsy at the time of biopsy (41/281= 15%), patient withdrawal of consent (23/281= 8%), pre-analytical factors preventing tissue or liquid biopsy analysis (14/281= 5%), unsuccessful analyses (13/281= 4%), other treatment initiated at time of planned biopsy (10/281= 4%), unknown reasons (9/281= 3%) or biopsy contraindicated (4/281= 1%). Conclusion: The main cause of unsuccessful GP in this study was pre-analytical factors, primarily linked to performance status decline. Performing the biopsy and GP in earlier treatment lines, may reduce failure rates. Furthermore, considering the risk of rapid performance status decline, prior to biopsy referral, along with reduced lag time from obtaining consent to biopsy, may enhance GP success rates. Citation Format: Cecilie Iden, Laila Belcaid, Ida Jacobsen, Martin Hoejgaard, Iben Spanggaard, Morten Mau-Soerensen, Ulrik Lassen, Christina Westmose Yde, Kristoffer Staal Rohrberg. Comprehensive analysis of causes for unsuccessful genomic profiling in a Phase 1 setting [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C050.

Bortezomib Induced Peripheral and Severe Autonomic Neuropathy Characterized By Dizziness, Orthostatic Hypotension and Weight Loss

Background It is well known that Bortezomib (B), a proteasome inhibitor used in the treatment of Multiple Myeloma (MM) causes peripheral neuropathy in an estimated 75% of patients and compromises their quality of life. There are reports of dizziness, muscle weakness and other unusual neurologic complications caused by B. Among patients that received B based induction, we observed peripheral neuropathy as expected. In addition, in a small subset we observed profound weight loss, dizziness, orthostatic hypotension (OH) and diarrhea. Some patients with weight loss required appetite stimulants and patients with OH/dizziness required medication for symptom control. The conglomeration of symptoms frequently impairs patients' performance status requiring interruption of therapy. B was given in combination with lenalidomide and dexamethasone (VRD) but we feel the neuropathic symptoms are more due to B since the combination of just lenalidomide and dexamethasone is not known to cause such complications. There are few publications on autonomic neuropathy (AN) caused by B but we believe it is under recognized and under diagnosed. Herein we report a series of patients managed at our center that presented with significant weight loss and dizziness suggestive of AN, prompting us to explore further and bring awareness to this problem. Methods From January 2018 to July 2023, patients with MM treated in our own practice and patients induced by our referring practices and sent to our center for transplant were evaluated. We identified patients who complained of significant weight loss and dizziness and reviewed medical records, looked at the characteristics they exhibited, and identified a pattern of symptoms and clinical course. Statistics are descriptive and this retrospective study was approved by our Institutional review board. Results Sixteen patients were noted to have symptoms suggestive of AN. 13 of 16 received VRD and 3 received Daratumumab, B and dexamethasone-based induction. B was administered subcutaneously and given twice weekly. The median age was 62.5 years (range 51-76). Ten were African American and 6 White; 6 female, 4 had diabetes but no neuropathy, 10 had bone disease, 5 renal failure at presentation. The interval between initiation of therapy and AN symptoms was a median of 117 days (range 50-219) and the median B dose was 20.8 mg/M 2 (range 11.7-40.3 mg/M 2). All 16 patients had weight loss and was the most recognizable symptom. The median weight loss and percentage weight loss (compared to baseline weight) were 18.2 Kgs (range 6.7-39.14 Kgs) and 19% (range 6-41%) respectively. 10 of 16 patients had loss of appetite and 9 had diarrhea. Further treatment was held due to decline in performance status in 14 patients. Nine patients received appetite stimulants; 2 megestrol and 7 dronabinol. OH and an increase in heart rate in the standing position was seen in all 16 patients. 11 of the 16 patients had dizziness; 3 patients received fludrocortisone and one received midodrine. 14 of 16 patients also had peripheral neuropathy of whom 13 required medications for neuropathic pain and 14 required narcotic analgesics. Conclusion 14 of 16 patients received a transplant and 2 declined. Transplant was delayed by 6 months (range 2-11) to enable recovery and the end-point was weight gain, resolution of OH and clinical improvement. Post-transplant 4 patients had persistent diarrhea and 1 had persistent dizziness. One patient developed severe mucositis, dysphagia, poor appetite and required hyperalimentation, nasogastric feeding and a feeding gastrostomy tube. 9 of 14 patients had persistent peripheral neuropathy and are using medications. Two of the 16 patients progressed and received salvage treatment one of the two is now deceased. With a median follow up of 26.35 (range 8.47-53.6) months, the median survival since diagnosis is 28.72 months. Severe AN characterized by weight loss, dizziness, OH in association with loss of appetite, diarrhea and painful neuropathy is an under recognized complication of Bortezomib. This generally results in interruption of disease directed therapy and delays autologous transplantation. Transplantation without resolution of symptoms could possibly worsen the morbidity and delay post-transplant recovery. To the best of our knowledge, we are the first group to report a series of patients with this symptom complex and strongly feel it requires further study in a larger cohort.

Preventing Future Harm: Identifying the Drivers of an Unsafe Discharge to Improve Safety on an Inpatient Oncology Service.

Cancer Morbidity, Mortality, and Improvement Rounds is a series of articles intended to explore the unique safety risks experienced by oncology patients through the lens of quality improvement, systems and human factors engineering, and cognitive psychology. For purposes of clarity, each case focuses on a single theme, although, as is true for all medical incidents, there are almost always multiple, overlapping, contributing factors. The quality improvement paradigm used here, which focuses on root cause analyses and opportunities to improve care delivery systems, was previously outlined in this journal.This article describes the care of a young patient with aggressive breast cancer, declining performance status, and multiple hospital admissions who died shortly after being discharged home without essential medications or an adequate plan for follow-up. The patient's death due to her malignancy was unavoidable, but she had inadequate resources before her death, leading to avoidable suffering. This outcome resulted from a series of minor errors attributable to inadequate handoffs, challenges establishing realistic goals of care, and hierarchy within and between medical teams that resulted in major lapses at the time of discharge. We explore these issues and discuss how this case led to the establishment of programs designed to empower health care providers and increase engagement of outpatient oncologists at critical points of patients' disease courses.

Presenting Symptoms in Newly Diagnosed Myeloma, Relation to Organ Damage, and Implications for Symptom-Directed Screening: A Secondary Analysis from the Tackling Early Morbidity and Mortality in Myeloma (TEAMM) Trial.

Multiple myeloma (MM) patients risk diagnostic delays and irreversible organ damage. In those with newly diagnosed myeloma, we explored the presenting symptoms to identify early signals of MM and their relationships to organ damage. The symptoms were recorded in patients' own words at diagnosis and included diagnostic time intervals. Those seen by a haematologist >6 months prior to MM diagnosis were classified as precursor disease (PD). Most (962/977) patients provided data. Back pain (38%), other pain (31%) and systemic symptoms (28%) predominated. Patients rarely complain of 'bone pain', simply 'pain'. Vertebral fractures are under-recognised as pathological and are the predominant irreversible organ damage (27% of patients), impacting the performance status (PS) and associated with back pain (odds ratio (OR) 6.14 [CI 4.47-8.44]), bone disease (OR 3.71 [CI 1.88-7.32]) and age >65 years (OR 1.58 [CI 1.15-2.17]). Renal failure is less frequent and associated with gastrointestinal symptoms (OR 2.23 [CI1.28-3.91]), age >65 years (OR 2.14 [CI1.28-3.91]) and absence of back pain (OR 0.44 [CI 0.29-0.67]). Patients with known PD (n = 149) had fewer vertebral fractures (p = 0.001), fewer adverse features (p = 0.001), less decline in PS (p = 0.001) and a lower stage (p = 0.04) than 813 with de novo MM. Our data suggest subgroups suitable for trials of 'symptom-directed' screening: those with back pain, unexplained pain, a general decline in health or low-impact vertebral compression fractures.

Towards improvement of oncology care through digital technology: A snapshot of Resilience remote patient monitoring (RPM) system implementation across 19 hospitals in Europe.

1518 Background: In clinical trials, RPM based on patient reported outcomes (PROs) has been shown to reduce symptom burden, increase dose intensity, improve quality of life and overall survival, and is recommended by international guidelines in routine oncology practice during systemic treatment (Di Maio et al., Ann Oncol 2022). Resilience developed a digital RPM system for oncology (CE marked, class IIa medical device) which prompts patients weekly with a notification to complete a survey including common symptoms from the NCI’s PRO-CTCAE questionnaire. Severe or worsening symptoms trigger an alert notification to the patient’s cancer care team, as well as personalized self-management advice, empowerment and educational material to patients. In this study we report the real-world implementation of Resilience RPM system in France and Belgium. Methods: Aggregated system-level metrics were collected covering all participating hospitals between Nov 2021 - Dec 2022. Qualitative and quantitative assessments focused on patient and provider utilization of Resilience RPM system was done. The implementation included a continued interaction between Resilience and hospital personnel for training, coordination and technical support. Results: 19 hospitals deployed Resilience in France and Belgium, including two Organization of European Cancer Institutes (OECI)-designated cancer centers and community oncology hospitals. Three integrated RPM with their electronic medical record. Overall, 1262 pts were registered (age range, 20-94), 40% with breast, 20% gastrointestinal and 8% genitourinary cancers. In the last 6 months, the main RPM interface was the mobile app (70%). Patient adherence with weekly RPM surveys was 85%, with a median time from prompt receipt to survey completion of 5h20min. RPM retention for 3 months, regardless of disease status, was 80%. Irrespective of severity, the most commonly reported PROs were performance status decline (94%), pain (89%) and anorexia (82%). The most common severe alert notifications were for nausea (33%), pain (31%) and anorexia (23%). The median time to alert management by the care team was 12h (70% within 24h), with 70% of alerts managed by a nurse navigator follow-up call, 5% by a referral for internal/external appointments, 0.5% with an emergency room referral and 0.4% with a hospitalization referral. 87% (32/38) of providers were satisfied with integrating the solution into their organization and 80% (30/38) felt patients were better managed through use of Resilience RPM. Conclusions: Implementation of the Resilience RPM system was feasible across a diverse group of 19 cancer centers in France and Belgium, with high levels of patient and provider participation and engagement. Resilience RPM offers an evidence-based approach to improve the quality and patient-centeredness of cancer care.

Metastasectomy of spinal lesions from thyroid carcinomas

Patients with differentiated thyroid carcinomas (DTCs) have a favourable long-term survival. Spinal metastases (SMs) cause a decline in performance status (PS), directly affecting mortality and indirectly preventing the use of systemic therapies. Metastasectomy is indicated, if feasible, as it yields the best local tumour control. Our study aimed to examine the long-term clinical outcomes of metastasectomy for SMs of thyroid carcinomas. We collected data on 22 patients with DTC (16 follicular and six papillary carcinomas) and one patient with medullary carcinoma who underwent complete surgical resection of SMs at our institution between July 1992 and July 2017, with a minimum postoperative follow-up of five years. The cancer-specific survival (CSS) from the first spinal metastasectomy to death or the last follow-up was determined using Kaplan-Meier analysis. Potential factors associated with survival were evaluated using the log-rank test. We analyzed the clinical parameters and outcome data, including pre- and postoperative disability (Eastern Cooperative Oncology Group PS 3), lung and non-spinal bone metastases, and history of radioiodine and kinase inhibitor therapies. Lung and other bone metastases at the time of surgery were observed in ten and eight patients, respectively. Three patients experienced local tumour recurrences at the operated site. The five- and ten-year CSS rates in the 22 patients with DTC were 77% and 52%, respectively. Pre- and postoperative disability and operative site tumour recurrence were identified as risk factors for short postoperative survival. Metastasectomy for resectable SM from DTC yielded favourable results and has the potential to improve survival.

Investigating documented reasons for withdrawal from clinical trials for patients with advanced prostate cancer (PCa).

105 Background: In clinical trials, treatment efficacy rates are based on participants who can tolerate treatment through study endpoints. Attrition from clinical trials can potentially lead to biased results (PMID: 30379822). Many oncology clinical trials censor the subject data of participants because of early trial intervention discontinuation due to adverse events (AEs), withdrawal of consent, or loss to follow-up. Despite high attrition rates reported across various oncology clinical trials (10-38%), there is inconsistency regarding investigating the reasons for withdrawal (PMID: 23132290). We aim to identify the causes of the withdrawal of participants with advanced PCa from clinical trials. Methods: In this IRB-approved single-center retrospective study (Sept 2014 to Sept 2022), the OnCore Research Database was used to capture data on the participants with advanced PCa enrolled in clinical trials. The included trials were specific to prostate cancer, and mixed solid tumor trials were excluded. Endpoint reports from all included trials were assessed. Participants who discontinued treatment for any reason were included. The primary objective was to obtain reasons for clinical trial withdrawal before primary endpoints, identify potential clinical intervention areas, and determine potential areas of adjustment to future study designs to improve retention rates. Eligibility criteria: diagnosis of metastatic prostate cancer, receipt of protocol treatment until discontinuation, and documentation of a reason for discontinuation of the protocol treatment. Results: 272 pts from the 18 clinical trials met eligibility criteria and were included in the study. The most common reasons documented for discontinuation were: the progression of disease (46.69%), other reasons (15.44%), adverse events (5.15%), personal preference (15.81%), and completion of protocol treatment (11.76%) of the total number of enrolled participants. We noted a statistically significant difference between participants who withdrew for other reasons in the castration-resistant versus castration-sensitive setting (6.08% vs. 32.38%, p value=0.03). Notably, declining performance status and symptom progression were listed under the “other reasons” category. The documentation of patient withdrawal due to clinical symptoms was reported across multiple withdrawal categories. Conclusions: In approximately one-third of participants, the reason for protocol treatment discontinuation was not apparent (documented as patient preference and other reasons with no further specifications). Further exploration of the exact reasons contributing to therapy discontinuation in these patients will be critical to improving patient retention in clinical trials.

A Real-World Data Retrospective Cohort Study of HER2-positive, Early-Stage Breast Cancer in Patients 70 Years of Age or Older: Natural History, Treatment Patterns, and Outcomes

PurposeEarly-stage human epidermal growth factor receptor 2-positive (HER2-positive) breast cancers (BCs) are routinely treated with intense perioperative chemotherapy combined with HER2-targeted agents. There is thus an unmet need for knowledge about treatment patterns and outcomes among patients 70 years of age or older, as this is an under-represented subset of patients in large clinical trials. MethodsWe used a deidentified cohort derived from a nationwide electronic health record database to conduct a retrospective cohort study of patients with HER2-positive BCs. Descriptive statistics were used to evaluate tumor characteristics, treatment patterns across age groups, and pathologic complete response rates. We used Kaplan–Meier survival curves to estimate recurrence-free and overall survivals; Cox proportional methods were used for adjustments with covariates of interest, including age as a categorical variable. ResultsWe included 395 patients with HER2-positive stage I to III BCs who were 70 years of age or older. Most patients had tumors with high nuclear-grade T2 tumors, and received surgical treatment first. Most patients (61.7%) who received HER2 therapies underwent treatment in the adjuvant setting; paclitaxel and trastuzumab combination was the most commonly used adjuvant regimen. Older age was associated with increased hazard of recurrence or death. We did not detect significant evidence of decline in performance status, but there was modest weight drop after perioperative HER2 treatments. ConclusionFindings suggest that patients in this older-age cohort were treated with de-escalated perioperative strategies and had poorer outcomes; our findings should be validated in future studies.

A phase II randomized therapeutic optimization trial for patients with refractory metastatic colorectal cancer using circulating tumor DNA (ctDNA): Rapid 1 trial.

TPS280 Background: Patients with advanced colorectal cancer after progressing through first line therapy, have several FDA-approved systemic therapies that are associated with clinical benefit for a substantive minority of patients. Current clinical practice is to trial these various treatments in a step-wise fashion using CT scans every 3 months to evaluate effectiveness. This process requires 3-4 months between therapeutic interventions from which the patient may ultimately derive no clinical benefit, may have a performance status decline; limiting the number of possible interventions and increases risk for physical and financial toxicity. An alternative to the traditional CT-scan guided approach for disease assessment is a circulating tumor DNA (ctDNA) intervention. The Signatera ctDNA assay which utilizes 16 truncal mutations derived from a patient’s tumor, can be assessed every 2 weeks for a rapid determination of the effectiveness of a systemic therapy. This may allow patients to be exposed to many treatments during a short time, limiting toxicity, allowing for a quicker determination of clinical benefit and personalization of treatment. The aim of this study will be to compare the traditional scan-driven approach vs an intervention guided by ctDNA assessments, both arms using a pre-specified order of chemotherapy treatments. Methods: This is a phase 2 randomized study of patients with refractory metastatic adenocarcinoma of the colon or rectum. Participants are eligible after progression or intolerance to first line chemotherapy or recurrence within 6 months of adjuvant oxaliplatin based chemotherapy. They must have RECIST measurable metastatic disease that is not eligible for definitive management. Tissue from the primary and/or metastatic deposit is required for Signatera NGS analysis and subjects must have measurable ctDNA at sampling. Participants must be ≥18 years old without major organ dysfunction and have an ECOG performance status of 0 to 2. Subjects with Microsatellite High, deficient in DNA mismatch repair genes, or BRAF V600E mutations are excluded. Subjects will be randomized 1:1 to Arm A (ctDNA guided intervention) or Arm B (scan-guided control group). Patients in both arms will undergo systemic treatments in a standardized pre-specified order. Arm A will have ctDNA assessments every 2 weeks until an intervention shows a significant decrease, then every 4 weeks until Progressive Disease (PD) by scan or significant ctDNA increase. CT imaging will be performed every 12 weeks. Those in Arm B, will have CT imaging every 12 weeks and blood collected for post-hoc analysis every 4 weeks until PD by scan. The primary endpoint is overall survival. Secondary endpoints include progression free survival and overall response. Exploratory analysis with be performed of the microbiome. Enrollment continues to a maximum of 78 patients. Clinical trial information: NCT04786600 .

Bortezomib Induced Peripheral and Severe Autonomic Neuropathy Characterized By Dizziness, Orthostatic Hypotension, and Weight Loss

INTRODUCTION: It is well known that Bortezomib (B), a proteasome inhibitor used in the treatment of Multiple Myeloma (MM) causes peripheral neuropathy in an estimated 75% of patients and compromises their quality of life. There are reports of dizziness, muscle weakness and other unusual neurologic complications caused by B. Among patients that received B based induction, we observed peripheral neuropathy as expected. In addition, in a small subset we observed profound weight loss, dizziness, orthostatic hypotension (OH) and diarrhea. Some patients with weight loss required appetite stimulants and patients with OH/dizziness required medication for symptom control. The conglomeration of symptoms frequently impairs patients' performance status requiring interruption of therapy. B was given in combination with lenalidomide and dexamethasone (VRD) but we feel the neuropathic symptoms are more due to B since the combination of just lenalidomide and dexamethasone is not known to cause such complications. There are few publications on autonomic neuropathy (AN) caused by B but we believe it is under recognized and under diagnosed. Herein we report a series of patients managed at our center that presented with significant weight loss and dizziness suggestive of AN, prompting us to explore further and bring awareness to this problem. METHODS: From January 2018 to July 2022, patients with MM treated in our own practice and patients induced by our referring practices and sent to our center for transplant were evaluated. We identified patients who complained of significant weight loss and dizziness and reviewed medical records, looked at the characteristics they exhibited, and identified a pattern of symptoms and clinical course. Statistics are descriptive and this retrospective study was approved by our Institutional Review Board. RESULTS: Twelve patients were noted to have symptoms suggestive of AN. 11 of 12 received VRD and one received Daratumumab, B and dexamethasone based induction. B was administered subcutaneously and given twice weekly. The median age was 62.5 years (range 51-76). Eight were African American and 4 White; 8 female, 3 had diabetes but no neuropathy, 8 had bone disease, 2 renal failure at presentation. The interval between initiation of therapy and AN symptoms was a median of 107 days (range 50-219) and the median B dose was 20.8 mg/m2 (range 9-31 mg/m2). All 12 patients had weight loss and was the most recognizable symptom. The median weight loss and percentage weight loss (compared to baseline weight) were 19.5 Kgs (range 7-37 Kgs) and 21% (range 7-41) respectively. 7 of 12 patients had loss of appetite and 8 had diarrhea. Further treatment was held due to decline in performance status in all 12 patients. Six patients received appetite stimulants; 2 megestrol and 4 dronabinol. OH and an increase in heart rate in the standing position was seen in all 12 patients. 10 of the 12 patients had dizziness; 3 patients received fludrocortisone and one received midodrine. 11 of 12 patients also had peripheral neuropathy of whom 10 required medications for neuropathic pain and 10 required narcotic analgesics. 10 of 12 patients received a transplant and 2 declined. Transplant was delayed by 6 months (range 2-11) to enable recovery and the end-point was weight gain, resolution of OH and clinical improvement. Post-transplant 4 patients had persistent diarrhea and 1 had persistent dizziness. One patient developed severe mucositis, dysphagia, poor appetite and required hyperalimentation, nasogastric feeding and a feeding gastrostomy tube. 10 of 12 patients had persistent peripheral neuropathy and are using medications. Two of the 12 patients progressed and are receiving salvage treatment but there are no deaths. With a median follow up of 23 months (range 8-42), the median survival since diagnosis is 27 months. CONCLUSIONS: Severe AN characterized by weight loss, dizziness, OH in association with loss of appetite, diarrhea and painful neuropathy is an under recognized complication of Bortezomib. This generally results in interruption of disease directed therapy and delays autologous transplantation. Transplantation without resolution of symptoms could possibly worsen the morbidity and delay post-transplant recovery. To the best of our knowledge, we are the first group to report a series of patients with this symptom complex and strongly feel it requires to be studied further in a larger cohort of patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Bombarding Oligoprogression: Oncologic Outcomes Following Localized Radiotherapy in Oligoprogressive Non-Small Cell Lung Cancer Patients on Maintenance Systemic Therapy

<h3>Purpose/Objective(s)</h3> The purpose of this study is to evaluate the efficacy and toxicity of focal radiotherapy (RT) to all oligoprogressive sites to prolong the durability of current systemic therapy or meaningful clinical benefit (MCB) in patients with metastatic non-small cell lung cancer (NSCLC) and one to five sites of progressive disease. The primary endpoints include progression-free survival (PFS) and MCB. Secondary endpoints include overall survival (OS), local control (LC), event free survival (EFS), and toxicities of RT. <h3>Materials/Methods</h3> Treatment records at our institution were reviewed (2018 to 2021) and included if they had metastatic NSCLC, started maintenance systemic therapy, developed oligoprogression (1-5 sites), and all oligoprogressive sites amenable to and treated with RT with the intent for MCB. Prior RT was allowed. Kaplan-Meier survival analysis and log-rank testing were performed using R-Studio software. PD-L1 status and actionable mutations were also documented. Toxicities were documented using the CTCAE v5.0. <h3>Results</h3> From our records, 23 patients were identified and met inclusion criteria. Thirteen (57%) were female and 10 were male. Twenty-one (91%) of patients had adenocarcinoma, 10 (43%) had actionable mutations, and 13 (57%) had PD-L1 expression > 1%. 13 patients (56%) were on PD1/PD-L1 checkpoint inhibition, 7 (30%) patients were on EGFR-targeted therapy, and 3 (13%) patients were receiving chemotherapy alone. A total of 41 targets were irradiated with a median of 2 per patient (range 1 to 4), with 28 (68%) targets receiving stereotactic body radiotherapy or radiosurgery, 12 (29%) receiving intensity-modulated radiotherapy, and 1 (2%) receiving 3D conformal RT. At a median follow-up of 12.6 months, there were 17 progression events; 6 patients started next-line therapy and 6 were recommended no further therapy based on declining performance status or no suitable next line systemic therapy. Four patients received additional targeted radiotherapy for oligoprogression and did not switch therapies. Median PFS, OS, and EFS were 8.4 months (IQR 4.1 – 17.5), 17.2 months (IQR 12.6 – 31.4), and 8.3 months (IQR 2.7 – 12.0), respectively. At 12 months follow-up, 6 (43%) of 14 living patients maintained their systemic therapy without initiating next-line therapy. Median time to start of next line therapy (MCB) was not reached in this analysis due to few events. There was one local failure of an irradiated site yielding an in-field failure rate of 4%. Two patients (9%) had grade 3 chronic toxicity related to RT and were medically managed. <h3>Conclusion</h3> We identified that in oligoprogressive metastatic NSCLC patients, targeted RT to all progressive sites yielded high rates of LC and favorable rates of PFS and MCB. Future prospective trials with well-selected oligoprogressive patients are warranted to further evaluate the role of focal RT to oligoprogressive sites in this patient population.

Palliative Carboplatin Chemotherapy in Previously Treated High-Grade Glioma: Real-World Efficacy and Safety

Abstract AIMS Effective third-line chemotherapy options for patients after temozolomide (TMZ) and nitrosourea-based chemotherapy for high-grade glioma (HGG) are not well defined. The use of carboplatin is limited due to uncertainly around its effectiveness and tolerability. METHOD Patients with HGG treated with single-agent carboplatin chemotherapy between 2005-2021 were identified from our institutional database. Patient and treatment-related details were acquired from electronic hospital records. SPSS Statistics for Windows, (Version 23.0, IBM Corp.) was used for data analysis. RESULTS A total of 16 HGG patients were identified. This included 9 glioblastoma (GBM) and 3 anaplastic astrocytomas (AA). These 12 patients were used for further analysis. The median age was 48 (22-73) years. All patients initially received a flat dose of 450 mg intravenous carboplatin every 3-4 weeks. All had previously received high dose RT (54-60 Gy), and temozolomide and lomustine-based chemotherapy. Carboplatin was used as 3rd or 4th line treatment. The median number of cycles given was 3 (range: 1-12). Five had rapid decline in performance status after 1-3 cycles. Five patients required dose/ cycle length adjustment due to grade 1 or 2 haematological toxicity. Other than cumulative fatigue, no other &amp;gt;/= grade 2 toxicities were reported. None required inpatient management for treatment toxicities. Median progression-free survival on carboplatin was 3 months (range 1-11 months) and overall survival was 8 months (range 1–26 months). CONCLUSION Carboplatin is a viable treatment option for HGG with acceptable toxicity rates. However, careful patient selection remains key to attaining maximum benefit.

EP06.01-005 COVID-19 and Post-COVID Outcomes in Lung Cancer Patients: Experience from an Indian Cancer Center

EP06.01-005 COVID-19 and Post-COVID Outcomes in Lung Cancer Patients: Experience from an Indian Cancer Center

SPIN-01 RADIATION THERAPY ALONE VERSUS RADIATION THERAPY PLUS RADIOFREQUENCY ABLATION/VERTEBRAL AUGMENTATION FOR SPINE METASTASIS: TRIAL IN PROGRESS

BACKGROUNDSpine metastases are a common occurrence in cancer patients and result in pain, neurologic deficits, decline in performance status, disability, inferior quality of life (QOL), and reduction in ability to receive cancer-directed therapies. Conventional external beam radiation therapy (EBRT) is associated with modest rates of pain relief, high rates of disease recurrence, low response rates for those with radioresistant histologies, and limited improvement in neurologic deficits. The addition of radiofrequency ablation/percutaneous vertebral augmentation (RFA/PVA) to index sites together with EBRT may improve pain response rates and corresponding quality of life. METHODS/DESIGNThis is a single-center, prospective, randomized, controlled trial in patients with spine metastases from T5-L5, stratified according to tumor type (radioresistant vs. radiosensitive) in which patients in each stratum are randomized in a 2:1 ratio to either RFA/PVA and EBRT or EBRT alone. All patients are treated with EBRT to a dose of 20-30 Gy in 5-10 fractions. The target parameters are measured and recorded at the baseline clinic visit, and daily at home with collection of weekly measurements at 1, 2, and 3 weeks after treatment, and at 3, 6, 12, and 24 months following treatment with imaging and QOL assessments. DISCUSSIONThe primary objective of this randomized trial is to determine whether RFA/PVA in addition to EBRT improves pain control compared to palliative EBRT alone for patients with spine metastases, defined as complete or partial pain relief (measured using the Numerical Rating Pain Scale [NRPS]) at 3 months. Secondary objectives include determining whether combined modality treatment improves the rapidity of pain response, duration of pain response, patient reported pain impact, health utility, and overall QOL. The results from this study will be used to allow for comparisons to alternative treatment approaches. This trial was activated 5/2020 and is open to accrual.

Effect of adherence to treatment guidelines on overall survival in elderly non-small-cell lung cancer patients

ObjectivesMean age at diagnosis of lung cancer is increasing with increasing age in Western populations. The present study was designed to evaluate the effect of adherence to first-line treatment guidelines on overall survival (OS) in elderly patients with non-small-cell lung cancer (NSCLC) and reasons for non-adherence to treatment guidelines. Materials and methodsAll patients aged ≥ 65 years diagnosed with NSCLC in Ostrobothnia, Finland, during the years 2016 to 2020 were identified from hospital registries. Adherence of first-line treatment to contemporary treatment guidelines was analysed based on diagnosis, tumour stage and performance status (PS), as was the effect of adherence on OS. ResultsA review of hospital registries identified 238 NSCLC patients aged ≥ 65 years. Guideline adherence by stage decreased significantly with age, with 66.4% of patients aged 65 to 74 years, but only 33.3% of those aged > 80 years treated according to guidelines (p < 0.001). Other factors associated with non-adherence to guidelines included poor PS, frailty, and limited lung function. Of the patients with PS 0–2, 26.9% were under-treated according to guidelines. Reasons for under-treatment included comorbidities, decreased lung function, physician decision to reduce treatment intensity or recommend best supportive care, patient choice and PS decline before treatment initiation. Guideline adherence increased overall OS of elderly NSCLC patients in all stages. Elderly PS 2 patients appear to benefit from guideline adherence and active treatment. In contrast, active treatment did not benefit patients with PS 3–4. ConclusionsGuideline adherence was associated with increased OS in elderly NSCLC patients. Almost 10% of elderly and otherwise fit NSCLC patients were not treated according to guidelines and could have benefitted from more intensive treatment.

A Pilot Study of Durvalumab (MEDI4736) with Tremelimumab in Combination with Image-Guided Stereotactic Body Radiotherapy in the Treatment of Metastatic Anaplastic Thyroid Cancer.

Background: Metastatic anaplastic thyroid cancer (ATC) has a poor prognosis. This pilot study aims to evaluate tremelimumab plus durvalumab with stereotactic body radiotherapy (SBRT) to improve overall survival (OS). Methods: Eligible patients received up to 4 doses tremelimumab (75 mg) given q4 weeks and up to 1 year of durvalumab (1500 mg) given q4 weeks. SBRT at 9 Gy × 3 fractions was given within the first 2 weeks of the start of treatment. Paired biopsies (pretreatment and between 3 and 10 weeks after the first dose of the drug treatment) were done in the medically qualified patients. Major inclusion criteria are metastatic ATC, Eastern Cooperative Oncology Group (ECOG) performance status 0-2, no prior immunotherapy, and last anticancer treatment >7 days before starting the study. The primary endpoint was 1 year OS with the combination of durvalumab, tremelimumab, and SBRT in metastatic ATC patients with a target of 1 year OS in ≥2 out of 12 patients. Results: A total of 13 patients signed consent but only 12 patients ultimately participated in this trial. One patient who consented to the protocol became ineligible for this study due to continued decline in performance status. Patient characteristics were as follows: male (n = 6) with a median age of 71 years (range: 49-82), and ECOG = 1. Nine patients had prior neck radiation and nine patients had prior chemotherapy. Next-generation sequencing and PD-L1 staining were done in the nine patients where tissue was available. High microsatellite instability (MSI) corresponding to mismatch repair defect was noted in two patients. There were zero confirmed responses and only one patient had stable disease and was treated with ≥4 cycles of study drugs. The median time that the patients were under treatment was 11 weeks (1-28 weeks). MSI status did not affect treatment response. High MSI patients were on treatment for 8-14 weeks before disease progression. The median OS was 14.5 weeks with only 1 patient alive beyond 1 year. The presence of a BRAF or p53 mutation did not appear to affect treatment outcome. Conclusions: Tremelimumab and durvalumab with SBRT did not improve OS for ATC. Future research is needed to examine other novel immunotherapy combinations with or without radiotherapy in the treatment of ATC. Clinical Trial Registration: NCT03122496.

Progression-Free Survival and Local Control After SABR for up to 5 Oligometastases: An Analysis From the Population-Based Phase 2 SABR-5 Trial

Despite increasing utilization of SABR for oligometastatic cancer, prospective outcomes are lacking. The purpose of this study was to determine progression-free survival (PFS), local control (LC), and prognostic factors from the population-based phase 2 SABR-5 trial. The SABR-5 trial was a single-arm phase 2 study with the primary endpoint of toxicity, conducted at the 6 regional cancer centers across British Columbia (BC), Canada, during which time SABR for oligometastases was only offered on trial. Patients with up to 5 oligometastases (total or not controlled by prior treatment and including induced oligometastatic disease) underwent SABR to all lesions. Patients were 18 years of age or older, had an Eastern Cooperative Oncology Group score of 0 to 2, and had life expectancy ≥ 6 months. The secondary outcomes of PFS and LC are presented here. Between November 2016 and July 2020, 381 patients underwent SABR on trial. Median follow-up was 27 months (interquartile range, 18-36). Median PFS was 15 months (95% confidence interval [CI], 12-18). LC at 1 and 3 years were 93% (95% CI, 91-95) and 87% (95% CI, 84-90), respectively. On multivariable analysis, increasing tumor diameter (hazard ratio [HR], 1.09; P < .001), declining performance status (HR, 2.13; P < .001), disease-free interval <18 months (HR, 1.52; P=.003), 4 or more metastases at SABR (HR, 1.48; P=.048), initiation or change in systemic treatment (HR, 0.50; P < .001), and oligoprogression (HR, 1.56; P=.008) were significant independent predictors of PFS. Tumor diameter (sub-hazard ratio [SHR], 1.28; P < .001), colorectal histology (SHR, 4.33; P=.002), and "other" histology (SHR, 3.90; P < .001) were associated with worse LC. In this population-based cohort including patients with genuine oligometastatic, oligoprogressive, and induced oligometastatic disease, the median PFS was 15 months and LC at 3 years was 87%. This supports ongoing efforts to randomize patients in phase 3 trials, even outside the original 1 to 5 metachronous oligometastatic paradigm.

Durvalumab treatment initiation delays in patients with unresectable stage III non–small cell lung cancer treated at Veterans Health Administration facilities.

8556 Background: Durvalumab is an FDA-approved immunotherapy for the treatment of adults with UnResectable stage III non-small cell lung cancer (UR-NSCLC) without disease progression following concurrent chemoradiotherapy (CRT). There are limited real-world data regarding Durvalumab treatment initiation delays (TIDs) and reasons for them in the UR-NSCLC population. Methods: Patients with stage III UR-NSCLC receiving consolidation Durvalumab at the Veterans Health Administration (VHA) between January 1, 2017 and June 30, 2020 were selected from the VHA database using ICD-10, HCPCS, and J codes. All had the opportunity to be treated for 12 months and were followed from Durvalumab initiation through the earliest of their last VHA visit, loss to follow up, death, or the study’s end (and excluded if Durvalumab therapy was ongoing at the study’s end). Trained data abstractors determined the occurrence and reasons for TIDs (&gt; 6 weeks from end of CRT to initiation of Durvalumab as in the PACIFIC trial) by chart review. Results: 935 patients were eligible for analysis (median age = 69 years; 95% males; 16% with ECOG performance status &gt;1). TIDs occurred in 39% of the patients (Table). Durvalumab was initiated 61 days (median) from the end of CRT in TID patients vs. 31 days for those without TIDs. There were no significant (α&lt;0.05) differences in age, race, smoking status, histology, or ECOG performance status and no comorbidity differences (except in patients with a history of cerebrovascular accident, for whom TIDs were more likely) between the TID/No-TID patients. Patients without timely post-CRT scans were more likely to have a TID. Of the 367 patients who experienced TIDs, 200 had documented reasons for the delay, consisting of other (not categorized) (28.5%), physician preference (20%), toxicity (11%), patient preference (10.5%), decline in performance status (10%), system issues (9.5%), social reasons (9%), and progression (0.5%). Conclusions: This is one of the largest retrospective cohort studies reporting real-world data in patients with UR-NSCLC receiving Durvalumab. TIDs were associated with increased time to post-CRT scans. This potential issue can be improved with care coordination and involvement of cancer navigators. Additional studies are needed to assess the impact of TIDs on survival outcomes.[Table: see text]