Major Cancer Center Research Articles

Successful completion of large, low-cost randomized cancer trials at an academic cancer center.

Concerns about low accrual have long been a standard part of the discourse on cancer clinical trials, reaching even as far as the news media. Indeed, so many trials are closed before completing accrual that a cottage industry has recently developed creating statistical models to predict trial failure. We previously proposed four methodologic fixes for the current crisis in clinical trials: (1) dramatically reducing the number of eligibility criteria, (2) using data routinely collected in clinical practice for trial endpoints; then lowering barriers to accrual by (3) cluster randomization or (4) staged consent. We report our practical experience of applying these fixes to randomized trials at Memorial Sloan Kettering Cancer Center. We have completed seven single-center randomized trials, with several more underway and accruing rapidly, with a total accrual approaching 10,000. Many of the trials have compared surgical interventions, an area where trials have traditionally been hard to complete. Only one of these trials was externally funded. While low costs were possible due to the existing research infrastructure at our institution, such infrastructure is common at major cancer centers. Further research on innovative clinical trial designs is warranted, particularly in higher-stakes settings, and in trials of medical and radiotherapy interventions.

Health Disparities among Patients with Cancer Who Received Molecular Testing for Biomarker-Directed Therapy.

Health disparities present a barrier to successful oncology treatment. The potential for precision oncology to reduce health disparities has not previously been analyzed. We performed a retrospective analysis of 12,627 patients from six major cancer centers whose tumors underwent molecular testing at Caris Life Sciences between 2010 and 2020. Kaplan-Meier and Cox regression were used to describe and analyze overall survival. The molecular and demographic features of the cohort were analyzed by χ2 and ANOVA tests. Black patients composed 25% of the cohort and White patients 63%. Among this molecularly-tested cohort, there were minimal outcome differences based on race, geographic location, or poverty level. When analyzing the interaction of age, race, and sex, racial-based disparities were noted primarily for young non-White women in the study cohort but were more pronounced for men and women of all ages in the broader patient population within the Surveillance, Epidemiology, and End Results database. Mutations in five genes-APC, EGFR, STK11, TP53, and KRAS-were found to affect overall survival among our cohort, and their prevalence varied by race in specific tumor types. Real-world outcomes data in mutation-defined cohorts also provided additional context to previously reported therapeutic response trends. Our study shows that patients who undergo molecular testing display reduced racial health disparities compared with the general population, whereas persistent racial disparities are influenced by age and sex. Genomic-driven racial disparities should be examined at a tumor lineage-specific level. Increased access to molecular testing for all eligible patients may play a role in improving health equity. Significance: This study is the largest of its kind to analyze health disparities and genomic features among a diverse multiinstitutional cohort of patients who underwent molecular testing. Continuing to increase awareness of and access to molecular testing approaches may help to reduce cancer health disparities and improve outcomes for all patients.

Oligometastatic non-small cell lung cancer: Impact of local and contemporary systemic treatment approaches on clinical outcome.

Oligometastatic (OMD) non-small cell lung cancer (NSCLC) is a distinct but heterogeneous entity. Current guidelines recommend systemic therapy and consolidation with local ablative therapy (LAT). However, evidence regarding the optimal choice of multimodal treatment approaches is lacking, in particular with respect to the integration of immunotherapy. This real-world study identified 218 patients with OMD NSCLC (2004-2023, prespecified criteria: ≤5 metastases in ≤2 organ systems) from three major German comprehensive cancer centers. Most patients had one (72.5%) or two (17.4%) metastatic lesions in a single (89.9%) organ system. Overall survival (OS) was significantly longer with a single metastatic lesion (HR 0.54, p = .003), and female gender (HR 0.4, p < .001). Median OS of the full cohort was 27.8 months, with 29% survival at 5 years. Patients who had completed LAT to all NSCLC sites, typically excluding patients with early progression, had a median OS of 34.4 months (37.7% 5-year OS rate) with a median recurrence-free survival (RFS) of 10.9 months (13.3% at 5 years). In those patients, systemic treatment as part of first-line therapy was associated with doubling of RFS (12.3 vs. 6.4 months, p < .001). Despite limited follow-up of patients receiving chemo-immunotherapy (EU approval 2018/2019), RFS was greatly improved by adding checkpoint inhibitors to chemotherapy (HR 0.44, p = .008, 2-year RFS 51.4% vs. 15.1%). In conclusion, patients with OMD NSCLC benefitted from multimodality approaches integrating systemic therapy and local ablation of all cancer sites. A substantial proportion of patients achieved extended OS, suggesting a potential for cure that can be further augmented with the addition of immunotherapy.

Novel Antibody-Drug-Conjugates in Routine Clinical Practice for the Treatment of Metastatic Breast Cancer: Adherence, Efficacy and Tolerability - Real-World Data from German Breast Centers.

The third-generation antibody-drug conjugates (ADC), trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), recently obtained approval for metastatic breast cancer treatment across various subtypes and therapeutic contexts. This retrospective, multicentric study evaluated real-world tolerability, feasibility and efficacy in a pre-treated, real-world cohort at three major German breast cancer centers. 125 patients treated with T-DXd or SG from November 2020 to June 2023 were included (T-DXd: 77 patients; SG: 48 patients). The median treatment duration was 6.0 months for T-DXd and 3.5 months for SG therapy, with a median follow-up duration of 10.4 months for T-DXd (95% CI: 8.4-11.6) and 11.8 months for SG (95% CI: 8.0-14.4). Severe neutropenia (CTC≥III°) occurred in 33.3% during SG therapy, with a numerical reduction observed following primary, prophylactic use of G-CSF. T-DXd-associated pneumonitis occurred in 8 out of 77 patients (10.4 %). Median progression-free survival (mPFS) was 8.6 months (95% CI: 5.8-12.4) with T-DXd (HER2+: 10.8; HER2-low: 4.7) and 4.9 months (95% CI: 2.8-6.3) with SG (TNBC 4.9; HR+/HER2-: not reached). Median overall survival (OS) was 23.8 months (95% CI: 16.1-not estimable) with T-DXd (HER2+: 27.1; HER2-low: not reached), and 12.4 months (95% CI: 8.7-not estimable) with SG therapy (TNBC: 12.4, HR+/HER2-: not reached). 95.7% of the protocol-specified, therapeutic dose was administered for T-DXd and 89.6% for SG. Overall, this indicates good feasibility, tolerability, and effectiveness of ADC therapies in the real-world setting.

A New Approach to Breast Specimen Orientation: Avoiding Pitfalls with the Specimen Plate Concept.

Accurate specimen marking is crucial during breast cancer surgery to avoid misorientation, which can lead to inadequate re-excision and tumor recurrence. We studied the marking methods at various breast cancer centers to create a tool that would prevent specimen misorientation. An online questionnaire was used to survey marking procedures at major breast cancer centers in Hungary, and a tool was developed using a troubleshooting method. Twelve out of twenty units responded (60%). Nine use an institutionally standardized marking system. Less than half of the surgical teams found specimen mammograms to be unambiguous. In more than 70% of departments, pathologists were uncertain about breast specimen orientation. Ambiguous marking methods caused orientation errors in half of the cases, while unclear marking directions caused the rest. Most pathologists (85%) and surgeons (75%) believed that coronal plane specimen mammography would help solve the problem. A plastic specimen plate has been developed to anchor breast tissue to a coronal breast scheme as seen in mammography images, providing clear localization information throughout the surgical process. There is a lack of standardization in breast specimen orientation and marking in Hungary. An optimized orientation toolkit is being developed to ensure consistent interpretation of specimen mammograms by surgeons and pathologists.

Outcomes of older adults with early-stage triple-negative breast cancer (TNBC) receiving chemotherapy: a single-institution experience.

Despite lower chemotherapy use in older triple-negative breast cancer (TNBC) patients, their outcomes match younger counterparts. We compared outcomes in early-stage TNBC patients by age receiving chemotherapy at a major cancer center with a national TNBC database. Retrospective study using institutional data on stage I-III TNBC (ER/PR < 10%) women with neoadjuvant/adjuvant chemotherapy. Based on their ages at diagnosis, patients were stratified into four categories: ≤40, 41-59, 60-69, and ≥ 70 years. Demographic and clinical characteristics recorded included race, disease stage, ER/PR positivity, treatment regimen, lymphatic or vascular invasion (LVI), histologic grade, Ki-67 level, body mass index (BMI), and pathologic complete response (pCR) following neoadjuvant treatment and are summarized using descriptive statistics. The primary endpoints were overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS); all were estimated using the Kaplan-Meier method. Both univariate and multivariate(MV) Cox regressions were applied to evaluate the impact of important covariates on these time-to-event endpoints. Of the 2336 patients studied, 492 (21.1%) were ≤ 40 years old, 1239 (53.1%) were 41-59, 461 (19.7%) were 60-69, and 144 (6.2%) were ≥ 70. In the univariate regression model of OS/DFS/DDFS, age ≥ 70 was significantly associated with worse OS (p = 0.0217); other factors associated with worse OS were non-anthracycline-based chemotherapy, higher tumor stage, and neoadjuvant chemotherapy. The multivariate Cox regression model, adjusted for race and stage, showed no significant effects of age on OS; however, patients ≥ 70 years old who received non-anthracycline treatment combinations had worse DFS (hazard ratio = 0.349 vs. 1.049, p = 0.0293) and DDFS (hazard ratio = 0.317 vs. 1.016, p = 0.0251) than patients ≤ 40 years old. DFS from MV model after adjusting for age, race, and disease stage, the hazard ratio between anthracycline + taxane treatments and anthracycline + other treatments in patients ≥ 70 years old was statistically significantly lower than in patients ≤ 40 years old (hazard ratios [HRs] = 0.349 vs. 1.049, p = 0.0293). Our findings indicate that outcomes such as DFS are less favorable in older compared to younger patients with early-stage TNBC, primarily in those who did not receive an anthracycline based chemotherapy regimen.

Evaluation of the toxicity and outcomes of the combination of midostaurin and CLAG-M in patients with FLT3-mutated acute myeloid leukemia (AML): A multi-center retrospective analysis.

6523 Background: FLT3-mutated AML is associated with poor outcomes. Addition of midostaurin (multi-targeted kinase inhibitor) to standard “7+3” with cytarabine and daunorubicin significantly prolongs overall and event-free survival for these patients (Stone 2017). At the University of Washington/Fred Hutchinson Cancer Center (UW/FHCC), the standard regimen for newly diagnosed (ND) and relapsed/refractory (r/r) AML is cladribine, high-dose cytarabine, GCSF, and mitoxantrone (CLAG-M); midostaurin is added if FLT3-mutated (Halpern 2018). There is currently no peer-reviewed literature to support this combination for these patients. The purpose of this study is to evaluate the safety and efficacy of the combination of midostaurin with CLAG-M in FLT3-mutated AML patients and compare the toxicity profile to midostaurin plus 7+3. Methods: This is a retrospective multi-center review conducted at three major cancer centers. Through pharmacy records and/or an institutional AML database, we identified adults with FLT3-mutated AML undergoing (re)induction chemotherapy who received either CLAG-M (UW/FHCC, Swedish) or 7+3 (OHSU, Swedish). The primary outcome was toxicity profile of the combination as measured by rate of adverse events ([AE], CTCAE Version 5.0). Secondary outcomes included disease response per ELN2017 AML working group criteria and 28-day mortality (TRM) (Döhner 2017). Patients treated on a clinical trial and in whom midostaurin was started &gt; 30 days after day 1 of chemotherapy were excluded. Rates of AEs were compared using Fisher’s exact test. Results: Eighty patients treated between 10/2022-12/2023 were included; 35 patients received CLAG-M, and 44 patients 7+3. Baseline characteristics were similar across all institutions, with most patients having adverse or intermediate risk disease. AE rates were similar between the two cohorts, (Table 1) except diarrhea and bleeding events were more common in the 7+3 vs. CLAG-M cohort (p = 0.004 and p = 0.037, respectively). The rate of complete remission (CR) plus CR with incomplete blood count recovery (CRi) did not significantly differ between the two cohorts: CLAG-M, 86% versus 7+3, 70% for 7+3 (p =0.11). No TRM occurred. Conclusions: The toxicity profile of CLAG-M combined with midostaurin is comparable to the combination of 7+3 with midostaurin, and induces high remissions rates in adults with FLT3-mutated AML. [Table: see text]

Clinical Features and Genomic Epidemiology of Bloodstream Infections due to Enterococcal Species Other Than Enterococcus faecalis or E. faecium in Patients With Cancer.

Non-Enterococcus faecium, non-E. faecalis (NFF) enterococci are a heterogeneous group of clinically pathogenic enterococci that include species with intrinsic low-level vancomycin resistance. Patients with cancer are at increased risk for bacteremia with NFF enterococci, but their clinical and molecular epidemiology have not been extensively described. We conducted a retrospective review of all patients (n = 70) with NFF bacteremia from 2016 to 2022 at a major cancer center. The main outcomes assessed were 30-day mortality, microbiological failure (positive blood cultures for ≥4 days), and recurrence of bacteremia (positive blood culture <14 days after clearance). Whole-genome sequencing was performed on all available NFF (n = 65). Patients with hematological malignancies made up 56% of the cohort (77% had leukemia). The majority of solid malignancies (87%) were gastrointestinal in origin. The majority of infections (83%) originated from an intra-abdominal source. The most common NFF species were E. gallinarum (50%) and E. casseliflavus (30%). Most (61%) patients received combination therapy. Bacteremia recurred in 4.3% of patients, there was a 30-day mortality of 23%, and 4.3% had microbiological failure. E. gallinarum and E. casseliflavus isolates were genetically diverse with no spatiotemporal clustering to suggest a single strain. Frequencies of ampicillin resistance (4.3%) and daptomycin resistance (1.9%) were low. Patients with hematologic malignancy had infections with NFF enterococci that harbored more resistance genes than patients with solid malignancy (P = .005). NFF bacteremia is caused by a heterogeneous population of isolates and is associated with significant mortality. Hematological malignancy is an important risk factor for infection with NFF resistant to multiple antibiotics.

Abstract PO3-17-10: Real-World evidence for Pembrolizumab-based neoadjuvant chemotherapy in early-stage triple negative breast cancer: a single institution experience

Abstract Introduction The improved pathologic complete response (pCR) and event-free survival observed in Keynote-522 trial (NCT03036488) led to the adoption of (neo)adjuvant pembrolizumab (pembro)-based chemotherapy (CT) for high-risk early-stage triple-negative breast cancer (eTNBC) in various jurisdictions. However, Real-World Evidence (RWE) for (neo)adjuvant pembro in this setting would further support its ongoing funding and utilization. The aim of this study was to provide RWE for (neo)adjuvant pembro in eTNBC in the United Arab Emirates (UAE), where patients often present with more-advanced disease stages and poorer prognostic profiles compared with North America and Europe. Method This is a retrospective cohort study involving all patients treated with pembro-based neoadjuvant chemotherapy (NACT) for eTNBC at a major cancer center (Tawam Hospital) in the UAE between October 2021 and June 2023. Patient characteristics, clinicopathologic features, immune related adverse events (irAE) and disease outcomes were reported by descriptive statistics. An exploratory analysis was also conducted to examine the associations between pCR and HER-2 status (HER2 negative vs HER2 low) as well pCR and treatment interruption (&amp;lt; vs = &amp;gt; 2 weeks). ResultA total of 41 patients, with a median age of 44 years, were included in this study. All had an ECOG status of 0-1. The clinical and pathological characteristics are provided in Table 1. Pathogenic germline BRCA (gBRCA) mutations were detected in 8 (21%) of the 38 patients who underwent testing, including 6 with gBRCA1 and 2 with gBRCA2), with additional TP53 and SMARC4 detected in one patient each. Approximately 66% of the patients (n = 27) completed surgery post neoadjuvant pembro+CT, of whom 18 (67%) had breast conserving surgery and 9 (33%) had mastectomy. Of the patients who underwent surgery, 60% (n = 16/27) achieved pCR including 68% (13/19) of the IHC 0+ and 37.5% (3/8) of the HER2 1+ or 2+ ISH negative (p-value = 0.429, Chi Square test). Of the total population, 16 (40%) did not complete NACT; 1 lost to follow-up, 9 were still on ongoing therapy, 2 discontinued therapy due to toxicity, and 4 developed progressions including 1 locoregional relapse, and 3 metastatic diseases. Of the 32 patients who completed at least 3 months of pembro-NACT, 14 (34%) reported any grade irAE: skin toxicity (N = 3, 21%), hypothyroidism (N = 8, 57%), Hyperthyroidism (N = 1, 7%), Hepatitis (N = 4, 28.5%), adrenal insufficiency (N = 1, 7%), and pneumonitis (N = 1, 7%). With a median follow up of 4.5 months, pembro was postponed in 4 patients and permanently discontinued in 1 secondary to severe pneumonitis requiring ICU admission. All irARs were graded at I and II, except for 1 grade III dermatitis, and 1 grade III pneumonitis. Interruption of IO was required for irAE in 5 (36%) patients, and steroids were administered in 4 (29%). pCR was observed in 6 (40%) patients out of 15 who experienced treatment interruption due to IrAE or CT and 10 out of 13 (77%) in those who did not experience treatment interruption (p = 0.04895, Chi-square test). Conclusion The pCR rates for Pembro-based NACT in this RWE study, involving patients with an overall higher risk disease, appeared to be consistent with those observed in keynote-522. Interestingly, pCR rates did not seem to differ between HER2 negative and HER2 low groups. However, pCR rates appeared to be lower in patients who experienced treatment interruptions. Approximately half of the patients developed irAE but the majority of the adverse events were of lower grade and did not require treatment interruptions. Overall, the RWE observed in this study supports the ongoing funding and utilization of Pembro-based NACT in eTNBC. Updated data, including the pCR rate and toxicity, will be presented at the meeting once most of the patients have completed surgery. Table 1: Clinical and Pathological Characteristics of patients (Nf41) XX- XX Citation Format: Aydah Al-Awadhi, Mouza AlShebli, Lina Wahba, Tallal Younis. Real-World evidence for Pembrolizumab-based neoadjuvant chemotherapy in early-stage triple negative breast cancer: a single institution experience [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 PO3-17-10.

Length of Stay Prediction Models for Oral Cancer Surgery: Machine Learning, Statistical and ACS-NSQIP.

Accurate prediction of hospital length of stay (LOS) following surgical management of oral cavity cancer (OCC) may be associated with improved patient counseling, hospital resource utilization and cost. The objective of this study was to compare the performance of statistical models, a machine learning (ML) model, and The American College of Surgeons National Surgical Quality Improvement Program's (ACS-NSQIP) calculator in predicting LOS following surgery for OCC. A retrospective multicenter database study was performed at two major academic head and neck cancer centers. Patients with OCC who underwent major free flap reconstructive surgery between January 2008 and June 2019 surgery were selected. Data were pooled and split into training and validation datasets. Statistical and ML models were developed, and performance was evaluated by comparing predicted and actual LOS using correlation coefficient values and percent accuracy. Totally 837 patients were selected with mean patient age being 62.5 ± 11.7 [SD] years and 67% being male. The ML model demonstrated the best accuracy (validation correlation 0.48, 4-day accuracy 70%), compared with the statistical models: multivariate analysis (0.45, 67%) and least absolute shrinkage and selection operator (0.42, 70%). All were superior to the ACS-NSQIP calculator's performance (0.23, 59%). We developed statistical and ML models that predicted LOS following major free flap reconstructive surgery for OCC. Our models demonstrated superior predictive performance to the ACS-NSQIP calculator. The ML model identified several novel predictors of LOS. These models must be validated in other institutions before being used in clinical practice. 3 Laryngoscope, 134:3664-3672, 2024.

Goals of Care Among Patients With Advanced Cancer and Their Family Caregivers in the Last Years of Life

Understanding goals of care for terminally ill patients at the end of life is crucial to ensure that patients receive care consistent with their preferences. To investigate the patterns of goals of care among patient-caregiver dyads over the last years of the patient's life and the associations of the goals of care with patient-caregiver characteristics. This prospective cohort study of 210 patient-caregiver dyads involved surveys every 3 months from July 8, 2016, until the patient's death or February 28, 2022. Data from the last 2 years of the patients' lives were analyzed. Dyads, which comprised patients with stage IV solid cancer and their caregivers, were recruited from outpatient clinics at 2 major cancer centers in Singapore. Goals of care were examined via the tradeoffs between life extension and symptom management and between life extension and cost containment. The actor-partner interdependence framework was implemented using mixed-effects linear regressions. This study included 210 dyads (patients: mean [SD] age, 62.6 [10.5] years; 108 men [51.4%]; caregivers: mean [SD] age, 49.4 [14.6] years; 132 women [62.9%]). On average, 34% of patients (264 of 780 observations; range, 23%-42%) and 29% of caregivers (225 of 780 observations; range, 20%-43%) prioritized symptom management over life extension, whereas 24% of patients (190 of 780 observations; range, 18%-32%) and 19% of caregivers (148 of 780 observations; range, 8%-26%) prioritized life extension. Between cost containment and life extension, on average, 28% of patients (220 of 777 observations; range, 22%-38%) and 17% of caregivers (137 of 780 observations; range, 10%-25%) prioritized cost containment, whereas 26% of patients (199 of 777 observations; range, 18%-34%) and 35% of caregivers (271 of 780 observations; range, 25%-45%) prioritized life extension. Goals of care did not change as patients approached death. Patients prioritized symptom management if they experienced higher symptom burden (average marginal effect [SE], 0.04 [0.01]), worse spiritual well-being (average marginal effect [SE], -0.04 [0.01]), and accurate (vs inaccurate) prognostic awareness (average marginal effect [SE], 0.40 [0.18]) and if their caregivers reported accurate prognostic awareness (average marginal effect [SE], 0.53 [0.18]), lower impact of caregiving on finances (average marginal effect [SE], -0.28 [0.08]), and poorer caregiving self-esteem (average marginal effect [SE], -0.48 [0.16]). Compared with patients, caregivers expressed lower preferences for cost containment (average marginal effect [SE], -0.63 [0.09]). Patients prioritized cost containment if they were older (average marginal effect [SE], 0.03 [0.01]), had higher symptom burden (average marginal effect [SE], 0.04 [0.01]), had poorer spiritual well-being (average marginal effect [SE], -0.04 [0.01]), and their caregivers reported poorer caregiving self-esteem (average marginal effect [SE], -0.51 [0.16]) and more family support (average marginal effect [SE], -0.30 [0.14]). In this cohort study of patient-caregiver dyads, findings suggested the importance of interventions aimed at reducing discordance in goals of care between patients and caregivers and helping them develop realistic expectations to avoid costly, futile treatments.

Abstract LB143: Environmental assessment of alcohol-related policies and practices at US cancer organizations

Abstract In 1998, the International Agency for Research on Cancer (IARC) declared that the consumption of alcoholic beverages was a class I carcinogen to humans; the designation was reaffirmed in 2007 and 2010. Despite this, approximately 4% of new cancer cases worldwide in 2020 were attributable to alcohol intake. Growing evidence indicates that alcohol use increases the risk of cancers of the upper aerodigestive tract (oral cavity, pharynx, esophagus, and larynx) and lower digestive tract (colon, rectum, and liver). Over half of the 6.3 million cases of these cancers are considered preventable, underscoring notable gaps regarding alcohol consumption and cancer prevention. Despite (1) the longstanding designation of alcohol as an established carcinogen, (2) an increasing and consistent body of data noting alcohol as a leading contributor to the global cancer burden, and (3) the publication of policy statements by authoritative sources, it is unclear whether cancer-focused institutions are aware of these facts or are acting on these data (i.e., implementing evidence-based policies and practices to limit alcohol-related cancer risks for their employees, guests, or the public). Driven by these data and shortfalls, we developed a 22-item survey to inquire about cancer organizations' interpretation of current literature, existing policies, decision-making processes, inclination to act, and perceived responsibility to lead in the realms of public education and policy implementation to mitigate alcohol-related cancer risks in the public’s interest. The survey will be sent to over 100 leading U.S. cancer organizations, including NCI-designated- and other major cancer centers, cancer-oriented professional organizations, and cancer-research organizations. It underwent rigorous testing for clarity, brevity, and expected response time, also drawing upon the expertise of five survey-science professionals. The study is under institutional review board (IRB) review, and we anticipate the survey’s distribution in the first quarter of the calendar year 2024. We expect to share the survey instrument and results during the meeting. Citation Format: Meghan Si, Stephanie Martch, Sanjay Shete, Ernest Hawk. Environmental assessment of alcohol-related policies and practices at US cancer organizations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB143.

Effects of the Brief Simha Kriya Breathing Practice for Health Care Workers During the COVID-19 Pandemic.

Introduction: During the COVID-19 pandemic, health care workers (HCWs) experienced increased anxiety, depression, loneliness, and other mental health issues. HCWs need additional resources to cope with the mental health impact of their work. Yoga techniques could be helpful strategies to manage different stressors during times of uncertainty. Methods: This prospective, single-arm, trial examined the effects of a brief pranayama yoga practice on the wellbeing of HCWs during the height of COVID-19. HCWs were recruited through announcements and institutional websites at a large major cancer center in the southern United States. A short, prerecorded, 5-min breathwork video intervention called "Simha Kriya" was provided to participants, and they were encouraged to practice one to two times daily for 4 weeks. Participants completed self-report instruments at baseline and weeks 1 and 4, including: (1) Perceived Stress Scale (PSS); (2) Brief Resilient Coping Scale (BRCS); and (3) a questionnaire assessing the experience of COVID-19 among HCWs that had five subscales. HCWs also conducted a measure of breath holding time. Paired sample t-tests and mixed-effects analysis of variance models examined changes over time. Results: One hundred participants consented to the study, with 88 female, 60 white, 39 worked remotely, and 27 were clinical staff. Sixty-nine participants provided data at week 1 and 56 at week 4. Participants' adherence to the breathing exercises between weeks 1 and 4 was similar, with a mean of six times per week. At week 4, there were significant decreases in the COVID-19 Distress score (p < 0.0001) and COVID-19 Disruption (p = 0.013), yet no changes in the PSS. There were also significant increases in COVID-19 Stress Management (p = 0.0001) and BRCS scores (p = 0.012), but no changes in Perceived Benefits of COVID-19 and no changes in breath holding time. Discussion: Brief yoga-based breathing practices helped reduce pandemic-specific stress, improved resilience, and stress management skills in HCWs. Trial Registration Number: NCT04482647.

Derivation and external validation of a simple risk score for predicting severe acute kidney injury after intravenous cisplatin: cohort study

ObjectiveTo develop and externally validate a prediction model for severe cisplatin associated acute kidney injury (CP-AKI).DesignMulticenter cohort study.SettingSix geographically diverse major academic cancer centers across the US.ParticipantsAdults (≥18 years) receiving...

The impact of pre-treatment smoking status on survival after chemoradiotherapy for locally advanced non-small-cell lung cancer

IntroductionSmoking is a risk factor for the development of lung cancer and reduces life expectancy within the general population. Retrospective studies suggest that non-smokers have better outcomes after treatment for lung cancer. We used a prospective database to investigate relationships between pre-treatment smoking status and survival for a cohort of patients with stage III non-small-cell lung cancer (NSCLC) treated with curative-intent concurrent chemoradiotherapy (CRT). MethodsAll patients treated with CRT for stage III NSCLC at a major metropolitan cancer centre were prospectively registered to a database. A detailed smoking history was routinely obtained at baseline. Kaplan-Meier statistics were used to assess overall survival and progression-free survival in never versus former versus current smokers. ResultsMedian overall survival for 265 eligible patients was 2.21 years (95 % Confidence Interval 1.78, 2.84). It was 5.5 years (95 % CI 2.1, not reached) for 25 never-smokers versus 1.9 years (95 % CI 1.5, 2.7) for 182 former smokers and 2.2 years (95 % CI 1.3, 2.7) for 58 current smokers. Hazard ratio for death was 2.43 (95 % CI 1.32–4.50) for former smokers and 2.75 (95 % CI 1.40, 5.40) for current smokers, p = 0.006. Actionable tumour mutations (EGFR, ALK, ROS1) were present in more never smokers (14/25) than former (9/182) or current (3/58) smokers. TKI use was also higher in never smokers but this was not significantly associated with superior survival (Hazard ratio 0.71, 95 % CI 0.41, 1.26). ConclusionsNever smokers have substantially better overall survival than former or current smokers after undergoing CRT for NSCLC.

NovoSorb® biodegradable temporising matrix (BTM) in the reconstruction of cutaneous malignancies in a major cancer centre: a case series.

Non-graftable or composite defect reconstruction represents a major challenge to the reconstructive surgeon, with many wounds requiring local flap or free microvascular tissue transfer approaches. The recent advent of synthetic skin substitutes such as Biodegradable Temporizing Matrix (BTM) have revolutionized the management of complex defects including those caused by burns, trauma and infection, with low-morbidity and low-complexity surgery. However, limited data exist supporting their use in cancer reconstruction in Australia. We performed a prospective cohort study of patients undergoing cancer resection and reconstruction with BTM between February 2021 and February 2023 in our institution. Reported outcomes included matrix integration, infection, and return to theatre. Twelve patients underwent reconstruction of primary or secondary defects following cancer resection during this period. Eight patients were male, four female, mean age at surgery was 70 years. Pathology resected included squamous cell carcinoma (SCC) and melanoma of the head and neck, sarcoma resection of the lower limb, and osteoradionecrosis (ORN) of the scalp. T-stage of primary tumours ranged from T2 to T4 and one in-transit metastasis of melanoma. Four patients were treated with radiotherapy, two of whom received postoperative radiotherapy (PORT) and two who received neoadjuvant radiotherapy, three additional patients had an intervention to a previously irradiated wound bed for recurrence or ORN. Overall matrix integration was 83% (10/12), with a 50% integration rate (2/4) observed in the post-radiotherapy group, requiring return to theatre for alternative reconstructive approaches. We report our experience with a synthetic dermal matrix (BTM) in cancer reconstruction, the largest cohort of this type in the Australian literature. BTM represents an exciting reconstructive tool for the cancer reconstructive surgeon, with a high rate of success and low morbidity.

Overlapping cancer service areas: Delineation and implications

AbstractPrior research has defined cancer service areas (CSAs) anchored by major cancer centers in the U.S., such as members of the Association of American Cancer Institutes (AACI). Those CSAs have discrete boundaries and may not capture the increasingly interwoven cancer care markets. This is the first attempt to delineate possible overlapping CSAs. Specifically, we integrate the concept of shared memberships and other spatial attributes into the Speaker‐Listener Label Propagation (SLPA) algorithm, termed the spatially constrained SLPA (or ScSLPA), and apply it to six representative areas in the U.S. The results show that overlapping CSAs tend to form in areas that are more urbanized, with higher localization index (LI) values, larger populations, and shorter travel times than discrete CSAs. Two CSAs in Los Angeles and San Diego are consistent with the catchment areas (CAs) of the National Cancer Institute (NCI)‐designated cancer centers, and other CSAs are much smaller than the CAs of their anchoring cancer centers. The study has important implications for public health policy to advance cancer control and prevention efforts.

Establishing an Integrative Oncology Service: Essential Aspects of Program Development.

Over the last 2 decades, integrative oncology (IO) has seen exponential growth within cancer care. It aims to combine evidence-based complementary therapies with conventional treatments to improve the well-being and quality of life for individuals dealing with cancer. The proliferation of integrative medicine programs in major cancer centers globally reflects varying approaches shaped by cultural, demographic, and resource-based factors. Drawing upon the expertise of leaders in IO from the Society for Integrative Oncology (SIO) Clinical Practice Committee, this manuscript serves as a practical guide for establishing an IO practice. Collating insights from diverse professionals, including oncologists, integrative oncologists, supportive care physicians, researchers, and clinicians, the paper aims to provide a comprehensive roadmap for initiating and advancing IO services. The primary objective is to bridge the gap between conventional cancer care and complementary therapies, fostering a patient-centric approach to address the multifaceted challenges encountered by individuals with cancer. This paper delineates several key sections elucidating different aspects of IO practice. It delves into the core components necessary for an IO service's foundation, outlines the initial medical consultation process, and presents crucial tools essential for successful consultations. By consolidating insights and expertise, this manuscript seeks to facilitate the integration of IO into mainstream cancer care, ultimately enhancing patient outcomes and experiences.

Functions of patient- and family-centered pediatric cancer communication in Pakistan.

Communication is an essential aspect of high-quality patient- and family-centered care. A model for pediatric cancer communication developed in the United States defined eight communication functions. The purpose of this study was to explore the relevance of these functions in Pakistan as part of an effort to understand the role of culture in communication. Semi-structured interviews were conducted with 20 clinicians and 18 caregivers of children with cancer at two major cancer centers. Interviews were conducted in Urdu or English and transcribed and translated as necessary. Two independent coders used a priori codes related to the communication model as well as novel codes derived inductively. Thematic analysis focused on operationalization of the functional communication model. Clinicians and caregivers in Pakistan discussed the importance of all eight communication functions previously identified including: information exchange, decision-making, managing uncertainty, enabling family self-management, responding to emotions, supporting hope, providing validation, and building relationships. The operationalization of these functions was influenced by Pakistani cultural context. For example, information-exchange included the importance of addressing preconceptions and community myths, while managing uncertainty included strong references to religion and faith-based coping. Essential to all eight functions was trust between the family and the medical team. These findings support the use of this functional communication model in diverse pediatric oncology settings and emphasize the importance of trust. Culturally sensitive operationalization of these functions could inform the adaptation of tools to measure communication and interventions aimed at supporting the needs of parents of children with cancer.

Challenges and solutions to system-wide use of precision oncology as the standard of care paradigm.

The personalised oncology paradigm remains challenging to deliver despite technological advances in genomics-based identification of actionable variants combined with the increasing focus of drug development on these specific targets. To ensure we continue to build concerted momentum to improve outcomes across all cancer types, financial, technological and operational barriers need to be addressed. For example, complete integration and certification of the 'molecular tumour board' into 'standard of care' ensures a unified clinical decision pathway that both counteracts fragmentation and is the cornerstone of evidence-based delivery inside and outside of a research setting. Generally, integrated delivery has been restricted to specific (common) cancer types either within major cancer centres or small regional networks. Here, we focus on solutions in real-world integration of genomics, pathology, surgery, oncological treatments, data from clinical source systems and analysis of whole-body imaging as digital data that can facilitate cost-effectiveness analysis, clinical trial recruitment, and outcome assessment. This urgent imperative for cancer also extends across the early diagnosis and adjuvant treatment interventions, individualised cancer vaccines, immune cell therapies, personalised synthetic lethal therapeutics and cancer screening and prevention. Oncology care systems worldwide require proactive step-changes in solutions that include inter-operative digital working that can solve patient centred challenges to ensure inclusive, quality, sustainable, fair and cost-effective adoption and efficient delivery. Here we highlight workforce, technical, clinical, regulatory and economic challenges that prevent the implementation of precision oncology at scale, and offer a systematic roadmap of integrated solutions for standard of care based on minimal essential digital tools. These include unified decision support tools, quality control, data flows within an ethical and legal data framework, training and certification, monitoring and feedback. Bridging the technical, operational, regulatory and economic gaps demands the joint actions from public and industry stakeholders across national and global boundaries.