Active Cancer Therapy Research Articles

Variation in acute cholecystitis outcomes and processes of care in patients with cancer

BackgroundPatients undergoing active cancer therapy or with metastatic cancer are at increased risk for acute cholecystitis and often present to general surgeons for evaluation and management. There is a paucity of data regarding the treatment processes used in these patients and the clinical outcomes achieved. Optimal management of acute cholecystitis in patients with cancer requires understanding their unique risk profile and options for treatment. MethodsEmergency general surgery data were collected at 10 hospitals from July 1, 2019, to February 29, 2024. Patients presenting with acute cholecystitis were selected for analysis. Propensity score matching was used to create matched cohorts of patients by the presence or absence of an active malignancy. The primary outcome was 30-day mortality. Secondary outcomes included complications, length of stay, readmission, and discharge disposition. Processes investigated include treatment modality, time to operation, and surgical technique. ResultsThe analysis included 8,673 patients. Mean age was 53.2 ± 19 years, 61.4% were female, and 17.8% were non-White. In total, 3.3% of patients had an active malignancy. Risk-adjusted 30-day mortality was higher in the cancer cohort (odds ratio: 5.85, 95% confidence interval: 2.38–14.4, P < .001). Patients with cancer also had higher rates of infectious complications (odds ratio: 2.55, 95% confidence interval: 1.54–4.2, P < .001), including sepsis (odds ratio: 2.95, 95% confidence interval: 1.61–5.39, P < .001) and pneumonia (odds ratio: 6.67, 95% confidence interval: 1.75–25.3, P < .005). Patients with cancer were more likely to receive nonoperative management (odds ratio: 2.85, 95% confidence interval: 2.11–3.84, P < .001). ConclusionPatients with cancer presenting with acute cholecystitis experience worse clinical outcomes after controlling for other factors. Furthermore, there is variation in the treatment process with increased rates of nonoperative management. These results have implications for the management of this population, particularly in relation to the impact on concurrent oncologic treatment plans.

Aesthetics treatment with injectable fillers in patients with cancer: Safety and quality of life during active antineoplastic therapy.

e23245 Background: Patients treated with antineoplastic treatment,commonly experience physical changes,secondary to the disease,weight loss,stress,and cancer therapy side-effects.Injectable fillers,offer effective and safe soft-tissue manipulations improving patients’ positive body image.While FDA-approved fillers are used in various medical settings,data on the safety and implications on quality of life(QOL)in oncology patients during active cancer therapy are limited.The study aimed to assess oncology patients' safety,QOL and both physician and patients’ perceived skin changes when fillers are used during active cancer therapies. Methods: The study was conducted at the Women's Cancer Center and Dermatology Department between 2021-2023.Female oncology patients treated with antineoplastic therapies completed a validated QOL questionnaire,dermatologist and patient self-evaluation,prior and following aesthetic intervention.Patients were randomly assigned to receive aesthetic treatments. Results: 127 female patients diagnosed with cancer,and treated at a single cancer center were included in the study.Patient mean age was 57 years.Patient diagnoses included breast,ovarian,uterine,cervical,and other cancers(58%, 22%,7%,5%,8%,respectively).31 (24%) patients were randomized to receive filler treatment.106(83%)patients were not treated with fillers,patients were either not randomized to filler treatments,or attributing their abstention to their cancer diagnosis,potential risks shared by other patients,or their treating oncologist.Patients receiving fillers were treated with chemotherapy,chemotherapy and biological agents,biological agents,hormonal therapies,immunotherapy,biological and hormonal therapy(39%,23%,10%,19%,6%,3%,respectively).3 independent dermatologists assessed improved aesthetic parameters following filler treatment,patients appeared less ill,sad,distracted.6-8 weeks post filler injections,there was a markedly improved QOL score,and noticeable positive skin changes by dermatologists and patients evaluation.Patients appeared less tired,angry,worried(45%,38%,35%,respectively).Most patients were satisfied following injections(81%) and planned future aesthetic treatments.More than half of the patients(55%)had no adverse events.Thirteen patients experienced minor dermal side effects (grade 1,42%).While 1 patient developed delayed inflammatory reaction 6-months post injection(grade 2,3%). Conclusions: Aesthetic treatment with filler injections while on anti-cancer treatment,with minimal side effects,statistically improved patient QOL and dermatological measures,enhanced dermatologist and patient sense of positive body image,demonstrating that injectable fillers can be safely recommended to patients receiving anti-neoplastic therapies.

The DIET study: A randomized controlled trial of a high fiber diet intervention (HFDI) in patients (pts) with melanoma receiving immune checkpoint blockade (ICB).

9558 Background: Multiple studies support that the gut microbiome plays a key role in response to ICB. Habitual high dietary fiber intake is associated with improved response to ICB and high fiber diet interventions have been shown to favorably modulate the microbiome in non-cancer populations. We therefore conducted a randomized trial of HFDI versus healthy control diet in melanoma pts receiving ICB. Methods: 45 melanoma pts starting ICB (21 adjuvant, 12 neoadjuvant, 12 advanced unresectable) were enrolled. Pts were randomized 2:1 to HFDI (30 to 50 g/day by ramp-up) or control (20 g) stratified by BMI and treatment (tx) intent. Inclusion criteria included BMI 18.5-40 kg/m2 and willing to exclusively eat the provided diet. Exclusion criteria include diabetes, major gastrointestinal disease/surgery, probiotic, antibiotic, or steroid use within 14 days, smoker or heavy drinker, and average dietary fiber intake &gt; 20g/day. As a controlled feeding study, the weekly menu in both arms were isocaloric (matched to patient’s energy needs via 30% fat, 50% carbohydrates, 20% protein) and provided by MD Anderson Bionutrition Research Core for up to 11 weeks. Both diets followed cancer prevention recommendations with little to no processed meats or added sugars; no alcohol consumption; and dietary fiber intake scaled through whole, plant foods. Blood and stool samples were collected longitudinally. Compliance was defined by the proportion of calories consumed vs. provided. Results: 65 pts were consented. 20 pts (31%) screen failed largely due to current fiber intake &gt;20 g/day. 45 pts were randomized, and 44 pts have completed the study to date. ICB tx were PD1 monotherapy (n=22), ipilimumab + nivolumab (n=16), and nivolumab + relatlimab (n=7). 53% of pts were female and average BMI was 29.7 kg/m2. Average baseline fiber intake was 15.5 g/day. Compliance with the diet while on study was 83% (95% CI 79%-87%); however, 15 pts (33%) withdrew consent early due to challenges with adherence to the study. The rate of diet-related AEs was 45%, all Grade I/II including abdominal pain (11%), anorexia (5%), bloating (6%), constipation (18%), diarrhea (23%), flatulence (18%), hyperglycemia (2%), nausea (2%) and weight loss (9%). The rate of Grade III/IV immune related adverse events was 25%. Conclusions: In this fully-controlled feeding study among melanoma pts undergoing ICB tx, both arms of the intervention were well-tolerated. In contrast to our prior studies in cancer survivor populations, we noted a significant discontinuation rate, perhaps due to the challenges of participating in a fully-controlled feeding study while undergoing active cancer therapy. Ongoing analyses are interrogating the effects of the dietary intervention on the structure and function of the gut microbiome, circulating and stool metabolites, and systemic and anti-tumor immunity. Clinical trial information: NCT04645680 .

Abstract PO2-11-07: Early Integration of Exercise into Breast Cancer Care: The MSK Healthy Living Program

Abstract Background: In patients with early-stage breast cancer, quality of life (QoL) worsens within 3-6 months following diagnosis. Physical activity (PA) can mitigate the adverse effects of treatment and improve QoL, and low PA level is associated with cancer recurrence and mortality. However, PA interventions are not included in standard cancer care. Early intervention to increase PA levels may improve QoL during active cancer therapy. The Healthy Living Program (HLP) at Memorial Sloan Kettering Cancer Center (MSK) is a lifestyle and survivorship program that engages early-stage breast cancer patients at the time of diagnosis using lifestyle risk stratification and matched referrals. We investigated whether early exercise intervention through the MSK HLP impacts QoL within the first months after cancer diagnosis. Methods: At the time of diagnosis, patients complete a lifestyle questionnaire (LQ), which is a composite of validated instruments, including the Godin Leisure Time Exercise Questionnaire (GLTEQ). Patients not meeting PA guidelines per the GLTEQ are offered a referral to an exercise physiologist (EP). The EP creates an individualized, home-based exercise program using the FITT Principle (Frequency, Intensity, Time, and Type). Patients meet with the EP every 4 weeks for 16 weeks; if exercise recommendations continue to be unmet, the program is extended. The Functional Assessment of Cancer Therapy-Breast (FACT-B) and 36-Item Short Form Survey Instrument (SF-36) were completed at baseline and the 16-week follow-up. Results: 252 patients enrolled between April 2020 – February 2023, of whom 92 volunteered to complete the QoL assessments. Median age was 53 years [range 23-84]; 12/252 (13.0%) of patients had ductal carcinoma in situ, 60/252 (65.2%) had Stage 1 disease, 17/252 (18.5%) had Stage 2 disease, and 3/252 (3.1%) had Stage 3 disease. 29/252 (31.5%) received chemotherapy, 62/252 (67.4%) received radiation, and 79/252 (85.9%) received hormone therapy. The mean baseline FACT scores were FACT-B: 116, FACT-G: 87, and FACT-B Trial Outcome Index (TOI): 73. At the 16-week follow-up, all QOL scores remained stable from baseline (means FACT-B: 118, FACT-G: 89, and TOI: 75). Improvements were observed among the subscales of the SF-36 from baseline to follow-up. The largest improvements were observed in physical and emotional role function scores, with 22% and 13% improvements from baseline to follow-up, respectively. Conclusions: A clinically implemented exercise intervention embedded in standard of care prevented decreases in QoL and improved physical and emotional functioning during the initial course of adjuvant breast cancer therapy. These findings support early implementation of lifestyle modification after a breast cancer diagnosis. Citation Format: Kylie Rowed, Sherry Shen, Andrea Smith, Bridget Kelly, Rocco Magnoli, Stacie Corcoran, Melissa Emerzian, Cynthia Cruz, Erica Salehi, Cara Anselmo, Mark Robson, Neil Iyengar. Early Integration of Exercise into Breast Cancer Care: The MSK Healthy Living Program [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-11-07.

Association between trajectories of prescription opioid use and risk of opioid use disorder and overdose among US nonmetastatic breast cancer survivors.

To examine the association between prescription opioid use trajectories and risk of opioid use disorder (OUD) or overdose among nonmetastatic breast cancer survivors by treatment type. This retrospective cohort study included female nonmetastatic breast cancer survivors with at least 1 opioid prescription fill in 2010-2019 Surveillance, Epidemiology and End Results linked Medicare data. Opioid mean daily morphine milligram equivalents (MME) calculated within 1.5years after initiating active breast cancer therapy. Group-based trajectory models identified distinct opioid use trajectory patterns. Risk of time to first OUD/overdose event within 1year after the trajectory period was calculated for distinct trajectory groups using Cox proportional hazards models. Analyses were stratified by treatment type. Four opioid use trajectories were identified for each treatment group. For 38,030 survivors with systemic endocrine therapy, 3 trajectories were associated with increased OUD/overdose risk compared with early discontinuation: minimal dose (< 5 MME; adjusted hazard ratio [aHR] = 1.73 [95% CI 1.43-2.09]), very low dose (5-25 MME; 2.67 [2.05-3.48]), and moderate dose (51-90 MME; 6.20 [4.69-8.19]). For 9477 survivors with adjuvant chemotherapy, low-dose opioid use was associated with higher OUD/overdose risk (aHR = 7.33 [95% CI 2.52-21.31]) compared with early discontinuation. For 3513 survivors with neoadjuvant chemotherapy, the differences in OUD/OD risks across the 4 trajectories were not significant. Among Medicare nonmetastatic breast cancer survivors receiving systemic endocrine therapy or adjuvant chemotherapy, compared with early discontinuation, low-dose or moderate-dose opioid use were associated with six- to sevenfold higher OUD/overdose risk. Breast cancer survivors at high-risk of OUD/overdose may benefit from targeted interventions (e.g., pain clinic referral).

Neutropenic ulcers in oncology: terminology, diagnosis, and management.

Neutropenic ulcerations are characterized by mucosal ulcerations which occur in the presence of neutropenia, suggesting a direct link between neutropenia and mucosal ulceration. An oral ulcer can be labeled as "neutropenic" only if the patients have primary (typically congenital) or secondary neutropenia, and neutropenia is the sole causative factor. Oral mucosal ulcers observed in patients undergoing oncologic therapy may also be termed as "neutropenic ulcers", but the pathogenesis of these oral ulcers more likely involves mucosal events related to trauma, microbial factors, and direct cytotoxicity. In cancer patients, the early appearance of oral ulcers is often attributed to oral mucositis which is a condition primarily caused by the direct mucosal cytotoxicity of chemotherapeutic agents and radiation therapy. Oral ulcers that develop later during or after active cancer therapy may result from intraoral trauma and typically manifest on non-keratinized areas of the oral mucosa which are more susceptible to mucosal damage. In patients undergoing chemotherapy, factors such as disturbances in mucosal barrier function as well as bone marrow suppression lead to reduced neutrophil count and function, and can contribute to the development of oral ulcers. While the etiology of oral ulcers in cancer therapy receiving patients can vary, it is important to emphasize that the host's response plays a crucial role in the progression and repair process of these lesions.This narrative review presents the etiopathogenesis, clinical presentation, and potential management approaches for oral ulcerations in neutropenic patients, with a particular focus on clarifying the usage of the term "neutropenic ulcer" since this term lacks diagnostic specificity and can be misleading in clinical practice regarding the underlying causes and treatment strategies.

Supporting gut health with medicinal cannabis in people with advanced cancer: potential benefits and challenges.

The side effects of cancer therapy continue to cause significant health and cost burden to the patient, their friends and family, and governments. A major barrier in the way in which these side effects are managed is the highly siloed mentality that results in a fragmented approach to symptom control. Increasingly, it is appreciated that many symptoms are manifestations of common underlying pathobiology, with changes in the gastrointestinal environment a key driver for many symptom sequelae. Breakdown of the mucosal barrier (mucositis) is a common and early side effect of many anti-cancer agents, known to contribute (in part) to a range of highly burdensome symptoms such as diarrhoea, nausea, vomiting, infection, malnutrition, fatigue, depression, and insomnia. Here, we outline a rationale for how, based on its already documented effects on the gastrointestinal microenvironment, medicinal cannabis could be used to control mucositis and prevent the constellation of symptoms with which it is associated. We will provide a brief update on the current state of evidence on medicinal cannabis in cancer care and outline the potential benefits (and challenges) of using medicinal cannabis during active cancer therapy.

Exploring the Use of a Digital Platform for Cancer Patients to Report Their Demographics, Disease and Therapy Characteristics, Age, and Educational Disparities: An Early-Stage Feasibility Study.

The increasing burden of cancer, the development of novel therapies, and the COVID-19 pandemic have made cancer care more complex. Digital innovation was then pushed toward developing platforms to facilitate access to cancer care. Age, education, and other disparities were, however, shown to limit the use of the digital health innovation. The aim of this early-stage feasibility study was to assess whether Greek cancer patients would register at CureCancer and self-report their demographics, disease and therapy characteristics, and socioeconomic issues. The study was organized by the Hellenic Society of Medical Oncology. Patients from nine cancer centers were invited to register on the CureCancer platform and complete an anonymous questionnaire on demographics, disease and therapy characteristics, and socioeconomic issues. Patients were also encouraged to upload, in a secure area for them, their medical files and share them with their physicians. They were then asked to comment on their experience of registration and how easy it was to upload their medical files. Of the 159 patients enrolled, 144 (90.56%) registered, and 114 of those (79.16%) completed the questionnaire, suggesting that the study is feasible. Users' median age was 54.5 years, and 86.8% of them were university and high school graduates. Most patients (79.8%) reported their specific type of cancer diagnosis, and all reported their therapy characteristics. Breast and lung cancers were the most common. A total of 87 patients (76.3%) reported being on active cancer therapy, 46 (40.4%) had metastatic disease, and 51 (44.7%) received supportive care medications. Eighty-one (71.05%) patients received prior cancer therapies, and twenty-seven recalled prior supportive care medications. All patients reported visiting non-oncology Health Care Professionals during the study. Nineteen of 72 (26.39%) patients who worked prior to cancer diagnosis changed work status; 49 (42.98) patients had children under 24 years; and 16 (14%) patients lived alone. Nine (7.9%) patients were members of patient associations. Registration was "much/very much" easy for 98 (86.0%) patients, while 67 (58.8%) had difficulties uploading their files. Patients commented on the well-organized data access, improved communication, feeling safe, medication adherence, interventions from a distance, and saving time and money. Over 80% of patients "preferred the digital way". A total of 114 patients succeeded in registering on the digital platform and reporting their demographics, disease and therapy characteristics, and socioeconomic issues. Age and educational disparities were disclosed and highlighted the need for educational programs to help older people and people of lower education use digital innovation. Health care policy measures would support patients' financial burden associated with work changes, living alone, and children under 24 years old at school or college. Policy actions would motivate patients to increase their participation in patient associations. According to the evidence DEFINED framework, the number of patients, and the focus on enrollment, engagement, and user experience, the study fulfills actionability level criterion 1.

Family perspectives on the transition from active treatment to survivorship for children with cancer.

Completing therapy for childhood cancer is an exciting milestone. However, this adjustment can be extremely stressful for patients and their families as they transition from cancer patient to survivor. A better understanding of the patient and family experience and their needs during this transition is crucial for developing guidelines and leveraging support for future patients and families. Participants were recruited from across the United States using a maximum variation sampling strategy. Families were eligible if they had a child diagnosed with cancer before age 15 and had completed treatment at least 1year prior to their interview. Participants completed a 90-180-minute semi-structured interview either in person or virtually. Interviews focused on the experiences of getting a diagnosis, experiences with treatment, information seeking, impact of cancer on the family, social support, and transitions to survivorship. Inductive thematic analysis revealed a wide variety of themes. This paper examines the transition from active cancer therapy into survivorship. Identified primary themes included (i) feelings about transitioning off therapy; (ii) coping with lingering effects; and (iii) experiences of transitioning off therapy and survivorship care. Subthemes highlighted the need for more support for both patients and families during this transition. Patients and families desire more support during the transition off therapy. Suggestions included access to additional resources, earlier transition to receiving survivorship care, and more holistic survivorship care. Further research is needed to determine best models and feasibility of delivering this desired support to all patients and families.

Autonomous metal-organic framework nanorobots for active mitochondria-targeted cancer therapy.

Nanorobotic manipulation to access subcellular organelles remains unmet due to the challenge in achieving intracellular controlled propulsion. Intracellular organelles, such as mitochondria, are an emerging therapeutic target with selective targeting and curative efficacy. We report an autonomous nanorobot capable of active mitochondria-targeted drug delivery, prepared by facilely encapsulating mitochondriotropic doxorubicin-triphenylphosphonium (DOX-TPP) inside zeolitic imidazolate framework-67 (ZIF-67) nanoparticles. The catalytic ZIF-67 body can decompose bioavailable hydrogen peroxide overexpressed inside tumor cells to generate effective intracellular mitochondriotropic movement in the presence of TPP cation. This nanorobot-enhanced targeted drug delivery induces mitochondria-mediated apoptosis and mitochondrial dysregulation to improve the in vitro anticancer effect and suppression of cancer cell metastasis, further verified by in vivo evaluations in the subcutaneous tumor model and orthotopic breast tumor model. This nanorobot unlocks a fresh field of nanorobot operation with intracellular organelle access, thereby introducing the next generation of robotic medical devices with organelle-level resolution for precision therapy.

COVID-19 severity and cardiovascular outcomes in SARS-CoV-2-infected patients with cancer and cardiovascular disease

BackgroundData regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited. ObjectivesTo compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF. MethodsRetrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD or no established CVD, male ≥ 55 or female ≥ 60 years, and one additional CVRF. The primary endpoint was an ordinal COVID-19 severity outcome including need for hospitalization, supplemental oxygen, intensive care unit (ICU), mechanical ventilation, ICU or mechanical ventilation plus vasopressors, and death. Secondary endpoints included incident adverse CV events. Ordinal logistic regression models estimated associations of CVD/CVRF with COVID-19 severity. Effect modification by recent cancer therapy was evaluated. ResultsAmong 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54–74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11–1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all p<0.001). CVD/CVRF was associated with worse COVID-19 severity in patients who had not received recent cancer therapy, but not in those undergoing active cancer therapy (OR 1.51 [95% CI 1.31–1.74] vs. OR 1.04 [95% CI 0.90–1.20], pinteraction <0.001). ConclusionsCo-morbid CVD/CVRF is associated with higher COVID-19 severity among patients with cancer, particularly those not receiving active cancer therapy. While infrequent, COVID-19 related CV complications were higher in patients with comorbid CVD/CVRF. (COVID-19 and Cancer Consortium Registry [CCC19]; NCT04354701).

Sexual dysfunction in women with lung cancer: Updates from the SHAWL study.

9071 Background: Despite its direct correlation with quality of life, sexual dysfunction is under-discussed and underreported in patients with lung cancer (LC). Sexual dysfunction is highly prevalent in patients with LC, with issues persisting over time; however, most data precede the approval of targeted therapies and immune checkpoint inhibitors. We report updated data from the SHAWL study, focusing on women’s sex life satisfaction. Methods: This cross-sectional, international survey study was administered via the GO2 Foundation Lung Cancer Registry. We utilized the Patient-Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction Measures for data collection. Participants were recruited from June 2020 to June 2021. Eligibility criteria included age &gt; 18 years, self-identification as a woman, and an LC diagnosis within ten years. Participants were asked about sexual health pertaining to 30 days before survey completion, now referred to as “recent.” Results: The survey was administered to 249 women (median age: 61 years). Most (67%) had stage IV LC and 47% were receiving targeted therapy; 66% were undergoing active treatment. Before LC diagnosis, 49% (117) of participants reported having no sexual health issues. Most women (54%, 128) indicated having had recent sexual activity, though 77% (183) reported moderate to severe sexual dysfunction. Indeed, only 7.5% (18) reported being quite or very interested in sexual activity, and only 6.7% (16) felt as if they always or often wanted to be involved in it. Out of the 128 women indicating recent sexual activity, the vast majority (72%, 91) also reported minimal to no satisfaction with their sex life, with 17% (22), 31% (39), and 24% (30) reporting none, a little bit, and some satisfaction, respectively. The most common reasons for lack of recent sexual activity were lack of interest (68%, 76) or vaginal dryness or pain (30%, 33). Most women (69%, 88) also reported rarely becoming sufficiently lubricated during sexual activity, with 54% (68) indicating that it was difficult to impossible to do so. Patients with stage IV diagnosis had a lower interest in and desire for sexual activity than those with non-metastatic LC. Patients not receiving active treatment reported similar rates of lack of interest and desire for sexual activity as those in active cancer therapy. Patients on targeted therapy had similar rates of sexual dysfunction as those receiving other LC treatments. Conclusions: The SHAWL study is the largest study evaluating sexual dysfunction and satisfaction in women with lung cancer in our current clinical environment. Sexual dysfunction, dissatisfaction, and lack of interest in sexual activity were highly prevalent in women with LC regardless of treatment status and type of therapy, suggesting that even after treatment completion, sexual issues persist. Sexual health should be integrated into thoracic oncology care for all patients with lung cancer.

Early integration of exercise into breast cancer care: The MSK healthy living program.

e24047 Background: In patients diagnosed with breast cancer, quality of life (QoL) has been reported to decrease during and after treatment. Physical activity (PA) mitigates adverse effects from treatment and improves QoL, and insufficient PA is associated with cancer recurrence and mortality. However, PA interventions are not included in standard cancer care. Early intervention to increase PA levels may improve QoL during active cancer therapy. The Healthy Living Program (HLP) at Memorial Sloan Kettering Cancer Center (MSK) is a lifestyle and survivorship program that engages early-stage breast cancer patients at the time of diagnosis using lifestyle risk stratification and matched referrals. We investigated whether early exercise intervention through the MSK HLP impacts QoL within the first months after cancer diagnosis. Methods: At the time of diagnosis, patients complete a lifestyle questionnaire (LQ), which is a composite of validated instruments, including the Godin Leisure Time Exercise Questionnaire (GLTEQ). Patients not meeting PA guidelines per the GLTEQ are offered a referral to an exercise physiologist (EP). The EP creates an individualized, home-based exercise program using the FITT Principle (Frequency, Intensity, Time, and Type). Patients meet with the EP every 4 weeks for 16 weeks; if exercise recommendations continue to be unmet, the program is extended. The Functional Assessment of Cancer Therapy-Breast (FACT-B) and 36-Item Short Form Survey Instrument (SF-36) were completed at baseline (BL) and follow-up (FU). Results: 206 patients enrolled between April 2020 – September 2022, of which 72 volunteered to complete the QoL assessments (median age 53 years [range 23-84]; 11.1% ductal carcinoma in situ, 69.4% Stage 1, 16.7% Stage 2, and 2.8% Stage 3). Among these patients, 30.6% received chemotherapy, 66.7% received radiation, 83.3% received hormone therapy, and 6% declined treatment. The mean baseline FACT scores were FACT-B: 116, FACT-G: 87, and FACT-B Trial Outcome Index (TOI): 72. At FU, scores were maintained with no significant changes (means FACT-B: 117, FACT-G: 88, and TOI: 74). Improvements were observed among the subscales of the SF-36 from BL to FU. The largest improvements were observed in physical and emotional role function scores, with 26% and 15% improvements from BL to FU, respectively. Conclusions: A clinically implemented exercise intervention embedded in standard of care prevented decreases in QoL and improved physical and emotional functioning during the initial course of adjuvant breast cancer therapy. These findings support early implementation of lifestyle modification after a breast cancer diagnosis.

Real-world behavioral restrictional practices of cancer patients (pts).

6592 Background: Quality of life (QoL) assessments do not measure pts’ ability to maintain normal daily activities during cancer therapy. Misbeliefs might promote avoidance of activities perceived as dangerous, compromising pts QoL. We examined the daily practices of actively treated pts with cancer. Methods: A locally validated questionnaire at the Tel-Aviv Sourasky Oncology Division was distributed internationally using the Belong.life social and professional digital health platform. We examined real-world pts reported practices, provided voluntarily and anonymously. The survey consisted of 15 questions, including demographic, clinical, behavioral parameters and sources guiding and supporting pts practices. Independent clinical and demographic variables were analyzed. Statistical analysis was performed, and a multivariate logistic regression was conducted to identify factors predicting restrictive behaviors. Results: The study population comprised 1,395 pts receiving active cancer therapy, reporting their outcomes from the Belong digital platform. Most respondents were from the United States (1082, 77.70%) and Israel (223, 16%), over the age of 40 (1309,93.8%),and female (987, 70.75%). Most common tumor types were breast (394,28.24%) and gastrointestinal cancers (199,14.26%). The majority of pts (1,005,72.88%) reported on at least 1 adopted limitation in daily activities, and 305 (21.86%) maintained more than half of these constraints. Daily life restrictions included avoiding sun exposure (779, 57.83%), international travel (417, 33.33%), indoor public places (malls, etc) (431, 33.13%), hair dyeing (271, 22.72%), domestic tourism (284, 21.93%), contact with friends and family (231, 17.69%), children and grandchildren (202, 16.33%), outdoor public spaces (190, 14.62%), and contact with pets (135, 10.41%). Multiple sources were implicated by the pts as guiding their behavior, with the most common being health-care professionals (951, 65.95%), followed by both non-medical authorities and health-care team (320, 22.19%), and non-medical advisors, including internet, pts forums, partners, friends, and family (171, 11.86%) Pts who maintained strict (≥50% of the limitations) and less strict restrictions, demonstrated no significant association between country of origin (p = 0.118), and education level (p = 0.3591). A significant association was noted between younger age (p = 0.0014), female sex (p = 0.0141) and primary cancer site (p &lt; 0.0001), and the adoption of strict restrictions. Conclusions: The majority of pts reported compromised daily activities, which are likely attributed to misconceptions about therapy and disease, deleteriously impacting QoL, therefore, impeding their ability to continue to conduct a complete and meaningful life. These findings require development of tools examining patients’ real-daily life activity as an additional endpoint in clinical trials.

P027 Immune checkpoint inhibitor associated vasculitis: a limitation to cancer therapy

Abstract Background/Aims The increasing use of immune checkpoint inhibitors (ICIs) underlies the importance of close monitoring and recognition of associated adverse events. We report a rare case of nivolumab-related peripheral vasculitis with digital gangrene and auto-amputation in a patient treated for mesothelioma. Methods A 69-year-old male with T4M0N0 pulmonary sarcoid mesothelioma was commenced on second-line Nivolumab therapy. 11 days later, he presented with worsening dyspnoea and dry cough. CTPA demonstrated new bilateral lower zone and peripheral predominant ground glass patchy consolidation consistent with acute pneumonitis. He sustained a significant clinical benefit from IV methylprednisolone and cessation of Nivolumab. 20 days after the pneumonitis episode, the patient re-presented with extremely tender, blue-black discoloration of the 2nd, 3rd and 4th fingers bilaterally, accompanied by localised sensory loss. Petechiae were also seen distributed across the digital pulp and nailbeds. Although bilateral, the left side was notably worse, with clear evidence of digital ischaemia and dry gangrene. Urine dipstix was bland. Immunology revealed normal C3/C4, ANCA and dsDNA serology, but mildly raised ANA (1.5). An echocardiogram excluded infective emboli. High dose IV methylprednisolone and iloprost infusion was commenced to treat ICI-associated peripheral vasculitis. Concurrently, dalteparin was required for a non-occlusive right subclavian venous thrombus. Nevertheless, his digital ischaemia progressed proximally to the left middle distal phalanx. MDT decision was made to avoid Cyclophosphamide given the infection risk. Sildenafil was introduced alongside a reduction regime of oral prednisolone. Unfortunately, the patient was subsequently hospitalised for acute PCP infection requiring high flow oxygen and intravenous antimicrobials. Following this stormy course, a slow but consistent and substantial clinical improvement was noted with respect to his digital ischaemia with minimal tissue loss. 7 months on, the patient’s digits remain free from ischaemia, infection and pain with good functional ability on Sildenafil treatment. Results Reports of PD-1 blockade-associated vasculitides mention ANCA-vasculitis, IgA vasculitis, leukocytoclastic vasculitis, eGPA and granulomatous vasculitis; however, drug-induced digit necrosis and auto-amputation is not widely reported. In this rare presentation of digital gangrene, immediate discontinuation of nivolumab treatment with initiation of high dose steroids and sildenafil, allowed eventual recovery of digits with limited auto-amputation and minimal sequelae. Management of nivolumab-associated vasculitis and pneumonitis required a multidisciplinary approach involving oncology, rheumatology, plastics and respiratory medicine. In the context of nivolumab discontinuation, the patient remains only on symptomatic treatment and follow up with no active cancer therapy meaning that prognosis is poor, in keeping with other reports of vasculitic reactions to nivolumab in cancer patients. Conclusion ICIs have revolutionised the management and outcomes across a range of malignancies. However, their mechanism can inadvertently induce undesired toxicity, the awareness of which is paramount. Disclosure M. Au: None. A. Faher: None. E. Htut: None.

Pandemic Phase-Adjusted Analysis of COVID-19 Outcomes Reveals Reduced Intrinsic Vulnerability and Substantial Vaccine Protection From Severe Acute Respiratory Syndrome Coronavirus 2 in Patients With Breast Cancer.

Although representing the majority of newly diagnosed cancers, patients with breast cancer appear less vulnerable to COVID-19 mortality compared with other malignancies. In the absence of patients on active cancer therapy included in vaccination trials, a contemporary real-world evaluation of outcomes during the various pandemic phases, as well as of the impact of vaccination, is needed to better inform clinical practice. We compared COVID-19 morbidity and mortality among patients with breast cancer across prevaccination (February 27, 2020-November 30, 2020), Alpha-Delta (December 1, 2020-December 14, 2021), and Omicron (December 15, 2021-January 31, 2022) phases using OnCovid registry participants (ClinicalTrials.gov identifier: NCT04393974). Twenty-eight-day case fatality rate (CFR28) and COVID-19 severity were compared in unvaccinated versus double-dosed/boosted patients (vaccinated) with inverse probability of treatment weighting models adjusted for country of origin, age, number of comorbidities, tumor stage, and receipt of systemic anticancer therapy within 1 month of COVID-19 diagnosis. By the data lock of February 4, 2022, the registry counted 613 eligible patients with breast cancer: 60.1% (n = 312) hormone receptor-positive, 25.2% (n = 131) human epidermal growth factor receptor 2-positive, and 14.6% (n = 76) triple-negative. The majority (61%; n = 374) had localized/locally advanced disease. Median age was 62 years (interquartile range, 51-74 years). A total of 193 patients (31.5%) presented ≥ 2 comorbidities and 69% (n = 330) were never smokers. In total, 392 (63.9%), 164 (26.8%), and 57 (9.3%) were diagnosed during the prevaccination, Alpha-Delta, and Omicron phases, respectively. Analysis of CFR28 demonstrates comparable estimates of mortality across the three pandemic phases (13.9%, 12.2%, 5.3%, respectively; P = .182). Nevertheless, a significant improvement in outcome measures of COVID-19 severity across the three pandemic time periods was observed. Importantly, when reported separately, unvaccinated patients from the Alpha-Delta and Omicron phases achieved comparable outcomes to those from the prevaccination phase. Of 566 patients eligible for the vaccination analysis, 72 (12.7%) were fully vaccinated and 494 (87.3%) were unvaccinated. We confirmed with inverse probability of treatment weighting multivariable analysis and following a clustered robust correction for participating center that vaccinated patients achieved improved CFR28 (odds ratio [OR], 0.19; 95% CI, 0.09 to 0.40), hospitalization (OR, 0.28; 95% CI, 0.11 to 0.69), COVID-19 complications (OR, 0.16; 95% CI, 0.06 to 0.45), and reduced requirement of COVID-19-specific therapy (OR, 0.24; 95% CI, 0.09 to 0.63) and oxygen therapy (OR, 0.24; 95% CI, 0.09 to 0.67) compared with unvaccinated controls. Our findings highlight a consistent reduction of COVID-19 severity in patients with breast cancer during the Omicron outbreak in Europe. We also demonstrate that even in this population, a complete severe acute respiratory syndrome coronavirus 2 vaccination course is a strong determinant of improved morbidity and mortality from COVID-19.

Clinical efficacy and long-term immunogenicity of an early triple dose regimen of SARS-CoV-2 mRNA vaccination in cancer patients

Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity. Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases. A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P<0.05) and chemotherapy (92.8%±18.1, P<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection. This study demonstrates the benefit of early administration of the third dose among cancer patients.

Neutralising antibody titers and COVID outcomes in cancer patients

Background: Cancer patients are at high risk of severe COVID infection and recommended at least three doses of SARS-CoV2 mRNA vaccines. Various anti-neoplastic treatments may affect long-term vaccine immunogenicity. Methods: Patients with solid or haematological cancer were recruited from two Singapore hospitals between July 2021 and March 2022. GenScript cPASS surrogate virus neutralisation assays measured antibody responses, which were correlated with clinical outcomes obtained from medical records and national mandatory-reporting databases. Results: In total, 273 patients were recruited (40 with haematological malignancies and the rest solid tumours). Two-hundred and four patients (74.7%) were receiving active cancer therapy: 98 (35.9%) receiving systemic chemotherapy and the rest targeted or immunotherapy. All patients were seronegative at baseline. After receiving one, two and three doses of SARS-CoV-2-mRNA vaccination, seroconversion rate was 35.2%, 79.4% and 92.4% respectively. After three doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) as compared to patients on immunotherapy (94.1%±9.56, p<0.05) and chemotherapy (92.8%±18.1, p<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients of which 18 were severe. Conclusion: This study demonstrates high immunogenicity of three doses of vaccines and protection against severe infection in cancer patients.

Disagreement between mothers' and fathers' rating of health-related quality of life in children with cancer

PurposeSerial assessment of health condition based on self-report made by children and their proxies has consistently shown a lack of congruence. The study explored the discrepancies between mother’s, father’s, and children’s reports on health-related quality of life (HRQOL) during the first two months of pediatric cancer treatment.MethodsIn this cohort study, children and parents completed the generic and cancer-specific Pediatric Quality-of-Life Inventory (PedsQL) questionnaires at initial diagnosis and in the subsequent months. Evaluation of discrepancies included intraclass correlations between mother–child and father–child dyads at different domain levels.ResultsThirty-six children with a diagnosis of cancer between May 2020 and November 2021 and their parents were included in this study. At diagnosis, mother–child dyads showed better agreement on more domains of the PedsQL Generic Core Scale than father–child dyads; moderate agreement persisted for both parents at subsequent time points on the physical domain. The disease-specific PedsQL Cancer Module revealed moderate and better agreement for mother–child dyads during active cancer therapy. In particular, agreement of mother–child dyads was pronounced for domains such as worry (0.77 [95% CI 0.52–0.89, P < 0.001]), whereas fathers tended to overestimate the child’s symptom burden for most of the remaining domains of the PedsQL Cancer Module.ConclusionThis cohort study shows that both parent proxy reports can provide valid information on child’s HRQOL, but that fathers tend to overestimate, particularly for non-observable domains. Proxy reports derived from mothers more closely agreed with children’s HRQOL and might be more weighted, if there is uncertainty between parents.

Unraveling the Plasma Protein Corona by Ultrasonic Cavitation Augments Active-Transporting of Liposome in Solid Tumor.

Ligand/receptor-mediated targeted drug delivery has been widely recognized as a promising strategy for improving the clinical efficacy ofnanomedicines but is attenuated by the binding of plasma protein on the surface of nanoparticles to form a protein corona. Here, it is shown that ultrasonic cavitation can be used to unravel surface plasma coronas on liposomal nanoparticles through ultrasound (US)-induced liposomal reassembly. To demonstrate the feasibility and effectiveness of the method, transcytosis-targeting-peptide-decorated reconfigurable liposomes (LPGLs) loaded with gemcitabine (GEM) and perfluoropentane (PFP) are developed for cancer-targeted therapy. In the blood circulation, the targeting peptides are deactivated by the plasma corona and lose their targeting capability. Once they reach tumor blood vessels, US irradiation induces transformation of the LPGLs from nanodrops into microbubbles via liquid-gas phase transition and decorticate the surface corona by reassembly of the lipid membrane. The activated liposomes regain the capability to recognize the receptors on tumor neovascularization, initiate ligand/receptor-mediated transcytosis, achieve efficient tumor accumulation and penetration, and lead to potent antitumor activity in multiple tumor models of patient-derived tumor xenografts. This study presents an effective strategy to tackle the fluid biological barriers of the protein corona and develop transcytosis-targeting liposomes for active tumor transport and efficient cancer therapy.