Chemotherapy Experience Research Articles

TNFRSF10D expression as a potential biomarker for cisplatin-induced damage and ovarian tumor relapse prediction

Among gynecological malignancies, ovarian cancer (OC) presents the most challenging diagnostic scenario. Despite exhaustive efforts, up to 90% of patients treated with taxane/platinum-based chemotherapy experience relapse, leading to poor survival rates. Identifying new molecular markers that can characterize disease aggressiveness, chemoresistance, recurrence risk, and metastasis is crucial. This study aimed to assess the susceptibility of three ovarian tumor cell lines (TOV-21G, SKOV-3, and OV-90) to cisplatin and paclitaxel, and to investigate the influence of these treatments on the mRNA expression of TANK, RIPK1, NFKB1, TNFRSF10D, and TRAF2. Among the cell lines, SKOV-3 ovarian adenocarcinoma cells demonstrated the highest resistance to cisplatin treatment (0.125mg/mL), followed by TOV-21G (0.076mg/mL) and OV-90 cells (0.028mg/mL). Regarding paclitaxel treatment, the SKOV-3 cell line exhibited the highest resistance (1.4µg/mL), followed by OV-90 (1.3µg/mL) and TOV-21G cells (0.9µg/mL). Gene expression analysis after paclitaxel treatment remained unchanged; however, after cisplatin treatment, TNFRSF10D was observed to be upregulated nearly 100-fold in SKOV-3 compared to all other cell lines studied. SKOV-3 is described as cisplatin and tumor necrosis factor-resistant. Despite the defective signaling of the TNFRSF10D receptor for apoptosis, it can activate the NFKB transcription factor through non-canonical TRAIL signaling, contributing to a pro-inflammatory immune response. In light of this, damage associated with cisplatin increases TNFRSF10D expression and may promote cell survival through non-canonical NFKB pathway activation. This suggests that resistance to TRAIL-induced apoptosis in these cells could serve as a promising chemoresistance biomarker in OC.

The molecular mechanisms of chemotherapeutic resistance in tumors (Review).

Chemotherapy remains a prevalent treatment for a wide range of tumors; however, the majority of patients undergoing conventional chemotherapy experience varying levels of chemoresistance, ultimately leading to suboptimal outcomes. The present article provided an in‑depth review of chemotherapy resistance in tumors, emphasizing the underlying factors contributing to this resistance in tumor cells. It also explored recent advancements in the identification of key molecules and molecular mechanisms within the primary chemoresistant pathways.

In-Breast Tumor Progression During Neoadjuvant Chemotherapy: Impact on and Factors Influencing Distant Recurrence-Free Survival.

Most patients with breast cancer treated with neoadjuvant chemotherapy (NAC) experience clinical benefit, however, a small proportion progress. We aimed to characterize factors predicting in-breast tumor progression and impact on distant recurrence. We reviewed all patients with clinical stage I-III breast cancer treated with NAC in 2006-2021 at our institution. We compared in-breast progressive disease (PD), defined as ≥ 20% increase in tumor size, with stable disease (SD) or response. Distant recurrence-free survival (DRFS) was analyzed using the Kaplan-Meier method and Cox proportional hazards regression. Of 1403 patients, 70 (5%) experienced in-breast PD, 243 (17%) SD, 560 (40%) partial response (PR), and 530 (38%) breast pathologic complete response (breast pCR, ypT0/Tis). The rate of PD varied by tumor subtype (8% in HR+/HER2-, 5% TNBC, 2% HER2+, p < 0.001). With median 48months follow-up, the rates of DRFS were significantly different according to clinical breast response as follows: PD 56%, SD 68%, PR 82%, or breast pCR 93%, p < 0.001. In patients with PD on multivariable analysis, post-NAC grade (adjusted HR 2.9, p = 0.002) and ypT3-4 category (adjusted HR 2.4, p = 0.03) were the strongest predictors of DRFS. Combining these factors, 23% had neither, 44% had one, and 33% had both, which stratified outcome in PD with 3-year DRFS of 100%, 77%, and 30%, respectively (p < 0.001). While in-breast PD during NAC is uncommon (5%), it predicts poor survival. Among patients with in-breast PD, post-NAC tumor grade and T category predict outcomes and may be useful to guide treatment escalation.

Effects of Network-based Positive Psychological Nursing Model on Negative Emotions, Cancer-related Fatigue, and Quality of Life in Cervical Cancer Patients with Post-operative Chemotherapy.

Cervical cancer patients with post-operative chemotherapy experience anxiety, depression, and cancer-related fatigue, leading to a decline in their quality of life and posing challenges to the rehabilitation of patients. Therefore, it is necessary to explore effective nursing methods. This study aimed to investigate the effects of a web-based positive psychological nursing model on negative emotions, cancer-related fatigue, self-management efficacy, treatment compliance, and quality of life among cervical cancer patients with post-operative chemotherapy. This retrospective study included 101 cervical cancer patients who underwent surgical intervention at our hospital between January 2019 and December 2023. Patients who received the usual mode of care were included in the control group (n = 48), while those who received the web-based positive psychological care mode were included in the study group (n = 53). For all study subjects, various assessment indices were evaluated, including baseline characteristics, treatment adherence, and the Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Revised Piper Fatigue Scale (RPFS), the Chinese version of the Strategies Used by Patients to Promote Health (C-SUPPH), and European Organization for Research and Treatment of Cancer Quality of Life questionnaire -Core 30 (EORTC QLQ-C30). Additionally, anxiety/depression, cancer-related fatigue, self-management efficacy, treatment compliance, and quality of life were compared between the two groups. After the intervention, the HAMA score, HAMD score, and RPFS score were significantly decreased for both groups compared to before intervention (p < 0.05). However, the C-SUPPH score was significantly increased than before intervention (p < 0.05). We observed that HAMA, HAMD, and RPFS scores were substantially lower in the study group than those in the control group after intervention (p < 0.05). In contrast, C-SUPPH scores were significantly higher (p < 0.05). After the intervention, treatment compliance was significantly better in the study group compared to the control group. Furthermore, the EORTC QLQ-C30 score was substantially higher than that of the control group (p < 0.05). The network-based positive psychological nursing model can effectively alleviate negative emotions and cancer-related fatigue in cervical cancer patients who have undergone post-operative chemotherapy, thereby improving their quality of life. Additionally, this model improves patients' self-management effectiveness and treatment compliance. These findings provide novel insights into the nursing of cervical cancer patients with post-operative chemotherapy, underscoring its clinical significance.

The impact of non- and anthracycline-based chemotherapy on fatigue in breast cancer survivors: results from WF-97415

PurposeTo examine the differential effect of non- and anthracycline-based chemotherapy on fatigue over 12 months post-diagnosis among breast cancer survivors.MethodsThis study is based on a prospective Wake Forest NCI Community Oncology Research Program (NCORP) multicenter cohort study (WF-97415) of women with stage I to III breast cancer and non-cancer controls. Analyses compared those: 1) receiving, or 2) not receiving anthracycline chemotherapy, 3) receiving aromatase inhibitors (AIs) without chemotherapy, with 4) a comparator group without a history of cancer. In-person clinic assessments were conducted at: baseline (prior to chemotherapy or start of AI therapy), and 3 and 12 months after baseline. The Functional Assessment of Chronic Illness Therapy-Fatigue scale was the primary outcome. Estimated least squares means by group using mixed models with a random subject effect, fixed effects of time and group, and the interaction between time and group was used to compare groups across time, controlling for age, comorbidities, and treatment variables.ResultsAmong 284 women (mean age = 53.4 years, sd 11.9 years), there was a significant (p < 0.0001) group by time interaction, with a sharp increase in fatigue at 3 months in the two chemotherapy groups in comparison to the non-chemotherapy and non-cancer controls. The two chemotherapy groups did not significantly differ in fatigue at any time point.ConclusionWomen with breast cancer who receive non- or anthracycline-based chemotherapy experience similar trends in and levels of fatigue within the first year of treatment and greater fatigue than women receiving AIs alone or women without breast cancer.

SURG-04. COMPARABLE SAFETY OF INTRATHECAL CHEMOTHERAPY GIVEN VIA LUMBAR PUNCTURE OR INTRAVENTRICULAR RESERVOIRS FOR PEDIATRIC CENTRAL NERVOUS SYSTEM (CNS) TUMORS: A SINGLE-INSTITUTION EXPERIENCE

Abstract BACKGROUND Intrathecal (IT) delivery of chemotherapy is utilized for the treatment of pediatric cancers, particularly leukemia and CNS tumors, either via lumbar puncture (LP) or intraventricular reservoir (IR). While the latter allows easier administration and more frequent IT dosing, data are lacking on the comparative safety and efficacy between these administration routes. We now present the IT chemotherapy experience from a single high-volume pediatric neuro-oncology center. METHODS We performed a retrospective chart review of patients with primary CNS tumors treated with IT chemotherapy between the years 2004-2022 at Dana-Farber/Boston Children’s Hospital. We collected demographic, clinical and outcome data. Safety evaluation included review of immediate (procedural) and short-term post-procedural assessments. RESULTS We identified 74 patients who received a total of 1,211 IT chemotherapy administrations. Excluding patients with insufficient data, we report on 38 patients who received 717 administrations (LP, n=207; IR, n=510). Median age was 26.5 months (range, 0.1-14.5), and diagnoses included medulloblastoma (n=14), ATRT (n=14) and others (n=10). Immediate events were reported in 11 (0.2%) IR and 1 (0.4%) LP administrations, i.e technical (n=5), high ICP (n=3), and immediate adverse side effects (n=3). Short-term events were reported in 16 (3%) IR and 12 (5.8%) LP administrations, i.e. fever (n=6), seizures (n=6), arachnoiditis (n=4), and others (n=10). No grade 4-5 adverse events were reported. No statistically significant difference was found between routes of administration and the rate of immediate or short-term events. Of note, 14/18 (78%) patients with CSF-positive disease achieved CSF clearance, with median time to response of 57 days (range, 27-446). CONCLUSIONS IT chemotherapy shows an excellent safety profile in children with malignant CNS tumors, with no differences between IR and LP administration. IT delivery can be efficacious in CFS clearance for patients with metastatic disease, lending support to inclusion of IT chemotherapy in current treatment regimens.

314P Real-world experience of carboplatin and gemcitabine combination chemotherapy in advanced biliary tract cancer: A single centre experience from Nottingham University Hospitals (UK)

314P Real-world experience of carboplatin and gemcitabine combination chemotherapy in advanced biliary tract cancer: A single centre experience from Nottingham University Hospitals (UK)

A real-world experience of hepatic arterial infusion chemotherapy combined with tislelizumab and lenvatinib for unresectable hepatocellular carcinoma with type IV portal vein tumor thrombus.

e16154 Background: Clinical improvement of interventional therapy with PD-(L)1 inhibitors plus molecular targeted therapies in have been confirmed by several studies, such as EMERALD-1, CHANCE001 etc. Limited data of this treatment in unresectable hepatocellular carcinoma (uHCC) patients (pts) with type IV portal vein tumor thrombus (PVTT) is available. This study aims to describe the efficacy and safety in uHCC pts with type IV PVTT (Vp4) who received HAIC combined with tislelizumab and lenvatinib (HAIC+Tisle+Len) in the real-world setting. Methods: This was a single-center, retrospective analysis of Vp4 uHCC pts treated with HAIC+Tisle+Len as first line systemic therapy between Apr 2020 and Dec 2022. Patient characteristics, treatment information, adverse events and survival data were collected. Pts received HAIC of modified FOLFOX (oxaliplatin, 85 mg/m2; leucovorin, 400 mg/m2; 5-fluorouracil bolus, 400 mg/m2 on day 1; 5-fluorouracil infusion, 2400 mg/m2 for 46 h), lenvatinib (8 or 12 mg once daily for body weight, 60 or ≥60 kg), and tislelizumab (200 mg q3w). HAIC was allowed to repeat on demands. Outcomes evaluated included overall survival (OS), progression free survival (PFS), overall response rate (ORR), overall disease control rate (DCR), and treatment-related adverse events (TRAEs). Results: A cohort of 54 pts was identified with a median age of 55 years (range 49-59). Pts characteristics were as follows: male (90.7%), hepatitis B (79.6%), BCLC C stage (100%), Child-Pugh A (88.9%), tumor number [ = 1 (50%), = 2 (7.4%), ≥3 (42.6%)], tumor diameter ≥10 cm (42.6%), extrahepatic metastasis (7.4%), beyond up to steven status (90.7%). As of Dec 20, 2023, the median follow-up duration was 21.3 mo (95% CI, 16.1-26.0), and the median number of HAIC was 3 (range 2-4). The median PFS was 8.1 months (95% CI, 6.8-12.3), while the median OS reached 16.8 months (95% CI:13.1-NR). ORR was 53.7% (3 CR, 26 PR) per RECIST 1.1; ORR was 66.7% (12 CR, 24 PR) per mRECIST. DCR was 96.3% per either RECIST 1.1 or mRECIST. Two pts received surgical treatment after conversion, one of whom underwent liver transplantation and remains tumor-free. The post-PD therapies after first-line treatment were as follows: Tisle+Len (24.1%), TACE+Tisle+Len (18.5%), Tisle+Len+Radiotherapy (7.4%), HAIC+Tisle+Regorafenib (5.6%), others (18.5%). The most common grade 3-4 TRAEs were hypertension (14.8%), decrease in albumin (11.1%), anorexia (9.3%), leukopenia (9.3%), abdominal pain (7.4%) and AST/ALT elevation (7.4%). Conclusions: The combination of HAIC with tislelizumab and lenvatinib represents a promising efficacy and manageable safety for uHCC pts with Vp4, which supplements the trial data for Vp4-HCC with real world outcomes.

An Indian real-world experience of intravenous fosnetupitant-palonosetron (IV NEPA) in preventing delayed and extended delayed CINV.

12070 Background: Although the reports suggest 15-25% cancer patients receiving highly- and moderately emetogenic chemotherapy (HEC and MEC) experience nausea and vomiting beyond day 5, majority of clinical trials focus on delayed chemotherapy induced nausea and vomiting (CINV) only during the first 5 days of treatment. Here we present a real world observational data with fixed combination of IntraVenous (Fos)NEtupitant and Palonosetron (IV NEPA) in preventing nausea/vomiting in delayed and extended delayed phase among patients receiving HEC/MEC. Methods: An open label, single arm, multicentre, phase IV prospective trial was conducted at six centres following individual Institutional Ethics Committee approval (CTRI/2023/04/051951). Patients in acute (0-24hrs), delayed (&gt;24-120hrs), extended delayed (&gt;120-240hrs) phases and extended overall phase (0-240hrs) were assessed for complete response (CR) (no vomiting and no need of rescue medication), complete protection (CP) [CR + no significant nausea (5mm to &lt;25mm) on visual analogue scale], complete control (CC) [CR + no nausea (&lt;5mm)] and safety. Results: Among 178 patients (Males-114, Females-64), 90 (50.56%) received HEC and 88 (49.44%) received MEC regimen. Cisplatin-Paclitaxel (19.10%) and Carboplatin-Paclitaxel (35.39%) were the most common HEC and MEC regimens respectively. Overall, CR in delayed and extended delayed phases were 93.26% and 96.07% respectively. Furthermore, CP and CC in delayed and extended delayed phases were 92.13% and 96.07% and 81.46% and 90.45% respectively (Table). In general, IV NEPA was well tolerated, as only 9.55% of patients experienced adverse events with 95.83% of them being mild in nature. Headache (2.25%) and injection site reactions (1.68%) were the most common adverse effect reported. Conclusions: IV NEPA demonstrated high efficacy and good tolerability in a real world Indian setting, exhibiting response rates of &gt;92% in both delayed and extended delayed phases in patients receiving HEC/MEC regimens. Clinical trial information: CTRI/2023/04/051951. [Table: see text]

Innovative infusion center assessments of chemotherapy-induced neurotoxicities: A pilot study supporting early and routine screenings as part of survivorship programs.

e24102 Background: More than 50% of patients treated with taxane and platinum chemotherapy experience neurotoxic adverse events due to treatment, including neuropathy, hearing loss or cognitive impairment. However, because risk factors and clinical trajectory of these toxicities remain poorly understood, it is not yet clear how or when patients should be screened. Innovative technology, such as tablet-based screening tools, create unique opportunities to capture patient symptoms, better understand potentially long-lasting side effects, and determine when to start either preventive or treatment/rehabilitation options. Methods: We assembled a multidisciplinary team from oncology, nursing, and audiology. IRB permission was obtained to perform a longitudinal observational pilot to assess the feasibility of performing chair-side neurotoxicity screenings in the infusion center of an urban safety net health system. Five infusion center nurses were recruited to collect data using a tablet-based application on 55 patients who met the inclusion criteria including chemotherapy-naive patients and fluent in English. Neuropathy and cognitive impairment were measured by validated standardized subjective scales (the Chemotherapy Induced Peripheral Neuropathy Assessment Tool, and the Attentional Function Index, respectively) and objective pure-tone audiometry (SHOEBOX Audiometry). Descriptive statistics were used to summarize outcome data. Results: Baseline assessments were completed on 48/55 patients with 37 completing at least one or up to 6 repeated assessments. All participants had baseline assessments before their first cycle by a chemo-certified RN in the infusion chair. Our sample included 55 adults aged 29 to 81 years, of whom 75% were females. 61% of participants were diagnosed with a gynecologic cancer, and 51% consented to receive Paclitaxel and Carboplatin chemotherapy regimen, 29% consented to receive Cisplatin chemotherapy, the remaining 20% consented to receive Oxaliplatin, Docetaxel, or Carboplatin alone. Significant changes occurred in all 3 symptoms by cycle 6 of chemotherapy with 45% of participants experiencing neuropathy, 13% experiencing a clinically significant change in hearing, and 30% experiencing self-reported cognitive concern by the 6th cycle. Ototoxicity and neurotoxicity scores followed the same trajectory of an increase or worsening in scores over time from cycle 1 to cycle 6. Conclusions: Use of innovative, portable tablet-based screening tool can be effectively used to capture symptoms of neuropathy chair-side as patients undergo chemotherapy. These observations support the need to better assess these approaches so that they can be used to optimize clinical outcomes and patient quality of life.

Association of Remote Patient-Reported Outcomes and Step Counts With Hospitalization or Death Among Patients With Advanced Cancer Undergoing Chemotherapy: Secondary Analysis of the PROStep Randomized Trial.

Patients with advanced cancer undergoing chemotherapy experience significant symptoms and declines in functional status, which are associated with poor outcomes. Remote monitoring of patient-reported outcomes (PROs; symptoms) and step counts (functional status) may proactively identify patients at risk of hospitalization or death. The aim of this study is to evaluate the association of (1) longitudinal PROs with step counts and (2) PROs and step counts with hospitalization or death. The PROStep randomized trial enrolled 108 patients with advanced gastrointestinal or lung cancers undergoing cytotoxic chemotherapy at a large academic cancer center. Patients were randomized to weekly text-based monitoring of 8 PROs plus continuous step count monitoring via Fitbit (Google) versus usual care. This preplanned secondary analysis included 57 of 75 patients randomized to the intervention who had PRO and step count data. We analyzed the associations between PROs and mean daily step counts and the associations of PROs and step counts with the composite outcome of hospitalization or death using bootstrapped generalized linear models to account for longitudinal data. Among 57 patients, the mean age was 57 (SD 10.9) years, 24 (42%) were female, 43 (75%) had advanced gastrointestinal cancer, 14 (25%) had advanced lung cancer, and 25 (44%) were hospitalized or died during follow-up. A 1-point weekly increase (on a 32-point scale) in aggregate PRO score was associated with 247 fewer mean daily steps (95% CI -277 to -213; P<.001). PROs most strongly associated with step count decline were patient-reported activity (daily step change -892), nausea score (-677), and constipation score (524). A 1-point weekly increase in aggregate PRO score was associated with 20% greater odds of hospitalization or death (adjusted odds ratio [aOR] 1.2, 95% CI 1.1-1.4; P=.01). PROs most strongly associated with hospitalization or death were pain (aOR 3.2, 95% CI 1.6-6.5; P<.001), decreased activity (aOR 3.2, 95% CI 1.4-7.1; P=.01), dyspnea (aOR 2.6, 95% CI 1.2-5.5; P=.02), and sadness (aOR 2.1, 95% CI 1.1-4.3; P=.03). A decrease in 1000 steps was associated with 16% greater odds of hospitalization or death (aOR 1.2, 95% CI 1.0-1.3; P=.03). Compared with baseline, mean daily step count decreased 7% (n=274 steps), 9% (n=351 steps), and 16% (n=667 steps) in the 3, 2, and 1 weeks before hospitalization or death, respectively. In this secondary analysis of a randomized trial among patients with advanced cancer, higher symptom burden and decreased step count were independently associated with and predictably worsened close to hospitalization or death. Future interventions should leverage longitudinal PRO and step count data to target interventions toward patients at risk for poor outcomes. ClinicalTrials.gov NCT04616768; https://clinicaltrials.gov/study/NCT04616768. RR2-10.1136/bmjopen-2021-054675.

Establishment, characterization, and genetic profiling of patient-derived osteosarcoma cells from a patient with retinoblastoma

Osteosarcoma is the most common malignant bone cancer in pediatric patients. Patients who respond poorly to chemotherapy experience worse clinical outcomes with a high mortality rate. The major challenge is the lack of effective drugs for these patients. To introduce new drugs for clinical approval, preclinical studies based on in vitro models must demonstrate the potency of the tested drugs, enabling the drugs to enter phase 1 clinical trials. Patient-derived cell culture is a promising testing platform for in vitro studies, as they more accurately recapitulate cancer states and genetic profiles compared to cell lines. In the present study, we established patient-derived osteosarcoma cells (PDC) from a patient who had previously been diagnosed with retinoblastoma. We identified a new variant of a germline mutation in the RB1 gene in the tissue of the patient. The biological effects of this PDC were studied to observe whether the cryopreserved PDC retained a feature of fresh PDC. The cryopreserved PDC preserved the key biological effects, including cell growth, invasive capability, migration, and mineralization, that define the conserved phenotypes compared to fresh PDC. From whole genome sequencing analysis of osteosarcoma tissue and patient-derived cells, we found that cryopreserved PDC was a minor population in the origin tissue and was selectively grown under the culture conditions. The cryopreserved PDC has a high resistance to conventional chemotherapy. This study demonstrated that the established cryopreserved PDC has the aggressive characteristics of osteosarcoma, in particular the chemoresistance phenotype that might be used for further investigation in the chemoresistant mechanism of osteosarcoma. In conclusion, the approach we applied for primary cell culture might be a promising method to generate in vitro models for functional testing of osteosarcoma.

Health-related Quality of Life in Patients with Previously Treated Advanced Urothelial Carcinoma from EV-301: A Phase 3 Trial of Enfortumab Vedotin Versus Chemotherapy

Background and objectiveIn comparison to chemotherapy, enfortumab vedotin (EV) prolonged overall survival in patients with previously treated advanced urothelial carcinoma in EV-301. The objective of the present study was to assess patient experiences of EV versus chemotherapy using patient-reported outcome (PRO) analysis of health-related quality of life (HRQoL). MethodsFor patients in the phase 3 EV-301 trial randomized to EV or chemotherapy we assessed responses to the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) at baseline, weekly for the first 12 wk, and then every 12 wk until discontinuation. We analyzed the QLQ-C30 change from baseline to week 12, the confirmed improvement rate, and the time to improvement or deterioration. Key findings and limitationsBaseline PRO compliance rates were 91% for the EV arm (n = 301) and 89% for the chemotherapy arm (n = 307); the corresponding average rates from baseline to week 12 were 70% and 67%. Patients receiving EV versus chemotherapy had reduced pain (difference in change from baseline to week 12: −5.7, 95% confidence interval [CI] −10.8 to −0.7; p = 0.027) and worsening appetite loss (7.3, 95% CI 0.90–13.69; p = 0.026). Larger proportions of patients in the EV arm reported HRQoL improvement from baseline than in the chemotherapy arm; the odds of a confirmed improvement across ten QLQ-C30 function/symptom scales were 1.67 to 2.76 times higher for EV than for chemotherapy. Patients in the EV arm had a shorter time to first confirmed improvement in global health status (GHS)/QoL, fatigue, pain, and physical, role, emotional, and social functioning (all p < 0.05). EV delayed the time to first confirmed deterioration in GHS/QoL (p = 0.027), but worsening appetite loss occurred earlier (p = 0.009) in comparison to chemotherapy. Conclusions and clinical implicationsHRQoL with EV was maintained, and deterioration in HRQoL was delayed with EV in comparison to chemotherapy. Better results with EV were reported for some scales, with the greatest difference observed for pain. These findings reinforce the EV safety and efficacy outcomes and benefits observed in EV-301. Patient summaryPatients with previously treated advanced cancer of the urinary tract receiving the drug enfortumab vedotin maintained their HRQoL in comparison to patients treated with chemotherapy.The EV-301 trial is registered on ClinicalTrials.gov as NCT03474107 and on EudraCT as 2017-003344-21.

Lurbinectedin in small cell lung cancer: real-world experience of a multicentre national early access programme.

Lurbinectedin is a novel oncogenic transcription inhibitor active in several cancers, including small cell lung cancer (SCLC). We aimed to describe the first Australian experience of the clinical efficacy and tolerability of lurbinectedin for the treatment of SCLC after progression on platinum-containing therapy. Multicentre real-world study of individuals with SCLC initiating lurbinectedin monotherapy (3.2 mg/m2 three-weekly) on an early access programme between May 2020 and December 2021. Key outcomes were clinical utilisation, efficacy and tolerability. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Outcome data were collected within the AUstralian Registry and biObank of thoRacic cAncers (AURORA). Data were analysed for 46 individuals across seven sites. Lurbinectedin was given as second- (83%, 38/46) or subsequent- (17%, 8/46) line therapy, mostly with prior chemoimmunotherapy (87%, 40/46). We report dose modifications (17%, 8/46), interruptions/delays (24%, 11/46), high-grade toxicities (28%, 13/46) and hospitalisations (54%, 25/46) during active treatment. The overall response rate was 33% and the disease control rate was 50%. Six-month OS was 44% (95% confidence interval (CI): 29.0-57.1). Twelve-month OS was 15% (95% CI: 6.5-26.8). From lurbinectedin first dose, the median PFS was 2.5 months (95% CI: 1.8-2.9) and OS was 4.5 months (95% CI: 3.5-7.2). From SCLC diagnosis, the median OS was 12.9 months (95% CI: 11.0-17.2). Individuals with a longer chemotherapy-free interval prior to lurbinectedin had longer PFS and OS. This real-world national experience of lurbinectedin post-platinum chemotherapy and immunotherapy for individuals with SCLC was similar to that reported in clinical trials.

Evaluating patient experience and healthcare utilisation in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

ObjectiveApproximately 30% of Australians reside in rural communities, where accessing healthcare facilities can be challenging due to considerable distance. This can result in disparities in healthcare equity, subsequently increasing risk of adverse health outcomes, delayed diagnosis, and diminished quality of life. These geographical constraints may be exacerbated in advanced cancers for which treatment is available only at selected centres with appropriate expertise. The aim of this study was therefore to explore the impact of patient residence on experience and healthcare utilisation following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).MethodsA retrospective study examined consecutive CRS and HIPEC patients at Royal Prince Alfred hospital from 2017 to 2022. Patients were stratified as metropolitan and regional based on their postcode. Demographics, experiential, and healthcare utilisation data were collected at multiple time points. Statistical analysis included chi-squared and T-tests.ResultsOf the 317 participants, 228 (72%) were from metropolitan and 89 (28%) from regional areas. Regional patients tended to rate their hospital experience as 'very good' (P=0.016). Metropolitan patients were more compliant with surgical follow-up (P<0.001). No other differences were observed in patient characteristics, experience or healthcare utilisation.ConclusionsThe geographical location of patients undergoing CRS and HIPEC for peritoneal malignancies at a major tertiary referral centre did not significantly influence their experience or healthcare utilisation outcomes. Future studies should evaluate long-term healthcare service utilisation or the ramifications of reduced follow-up on recurrence and survival, which will contribute to a deeper understanding of resource allocation in metropolitan and regional Australia, and illuminate its impact on clinical outcomes.

Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) experience in patients with recurrent low grade serous ovarian carcinoma (LGSOC): sub-cohort report of phase 1 clinical trial.

Low grade serous ovarian carcinoma (LGSOC) is a rare subtype of ovarian cancer (OC) that is challenging to treat due to its relative chemoresistance. Given that LGSOC patients often recur in the peritoneal cavity, novel intraperitoneal (IP) chemotherapy should be explored. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is a method that has demonstrated peritoneal disease control in cancers with peritoneal metastases. NCT04329494 is a US multicenter phase 1 trial evaluating the safety of PIPAC in recurrent ovarian, uterine, and GI cancers with peritoneal metastases. This analysis describes the outcomes of a sub-cohort of four LGSOC patients treated with IP cisplatin 10.5 mg/m2, doxorubicin 2.1 mg/m2 PIPAC q4-6 weeks. Primary endpoints included dose-limiting toxicities (DLT) and incidence of adverse events (AE). Secondary endpoints were progression free survival (PFS) and treatment response based on radiographic, intraoperative, and pathological findings. Four patients with LGSOC were enrolled of which three were heavily pretreated. Median prior lines of therapy was 5 (range 2-10). Three patients had extraperitoneal metastases, and two patients had baseline partial small bowel obstructive (SBO) symptoms. Median age of patients was 58 (38-68). PIPAC completion rate (≥2 PIPACs) was 75%. No DLTs or Clavien-Dindo surgical complications occurred. No G4/G5 AEs were observed, and one G3 abdominal pain was reported. One patient had a partial response after 3 cycles of PIPAC and completed an additional 3 cycles with compassionate use amendment. Two patients came off study after 2 cycles due to extraperitoneal progressive disease. One patient came off study after 1 cycle due to toxicity. Median decrease in peritoneal carcinomatosis index between cycles 1 and 2 was 5.0%. Ascites decreased in 2 out of 3 patients who had ≥2 PIPACs. Median PFS was 4.3 months (1.7-21.6), median overall survival was 11.6 months (5.4-30.1), and objective response rate was 25%. PIPAC with cisplatin/doxorubicin is well tolerated in LGSOC patients without baseline SBO symptoms. IP response was seen in 2 out of 3 patients that completed ≥2 PIPAC cycles. Further study of PIPAC for patients with recurrent disease limited to the IP cavity and with no partial SBO symptoms should be considered.

A commentary on 'The experience of neoadjuvant chemotherapy versus upfront surgery in resectable pancreatic cancer. A cross sectional study' - a correspondence.

A commentary on 'The experience of neoadjuvant chemotherapy versus upfront surgery in resectable pancreatic cancer. A cross sectional study' - a correspondence.

Prognostic Factors for Hyperglycemia in Patients Receiving Chemotherapy.

Approximately 10% to 30% of patients who receive chemotherapy experience hyperglycemia, which can affect the adverse reactions and treatment efficacy of chemotherapy. However, there is a paucity of research to explore the factors affecting hyperglycemia and include them in nursing interventions. The aim of this study was to understand the prognostic factors of hyperglycemia in cancer patients on chemotherapy. This retrospective, descriptive study included 134 adult patients with cancer receiving chemotherapy at Keimyeng University Dongsan Hospital in Daegu between July 1, 2021, and March 31, 2022. Data were analyzed using frequency, percentage, average, and standard deviation statistics and compared by t test, χ2 test, and logistic regression analysis. Logistic regression analysis revealed that sex (male) (95% confidence interval [CI], 7.24-745.49; odds ratio [OR], 73.48); education (95% CI, 4.02-201.59; OR, 28.46); exercise durations of 30 to 60 minutes (95% CI, 0.00-0.06; OR, 0.01), 60 to 90 minutes (95% CI, 0.00-0.05, OR = 0.01), and ≥90 minutes (95% CI, 0.00-0.42; OR, 0.03); exercise amount ≥ 2000 kcal/wk (95% CI, 0.01-0.77; OR, 0.06); and daily fat (95% CI, 1.02-1.14; OR, 1.08), protein (95% CI, 0.82-0.95; OR, 0.88), and seaweed (95% CI, 0.85-0.99; OR, 0.92) intake were significant predictors of hyperglycemia. The prognostic factors of hyperglycemia should be included in nursing interventions to prevent and manage hyperglycemia, which in turn may help reduce adverse reactions related to chemotherapy and improve treatment efficacy. To prevent and manage hyperglycemia in patients on chemotherapy, prognostic factors, including exercise and protein, fat, and seaweed consumption, should be considered in nursing interventions. Particularly, in men and patients with low education levels who are at a high risk of hyperglycemia, nursing interventions for diet and exercise should be individualized.

Phase I/II Study of Quizartinib, Venetoclax, and Decitabine Triple Combination in FLT3-ITD Mutated AML

Background: Patients (pts) newly diagnosed with FLT3-ITD mutated (m) acute myeloid leukemia (AML) who are ineligible for intensive induction chemotherapy (IC) experience poor outcomes (Konopleva et al. 2022, Clin. Can. Res.). These patients have a median overall survival (OS) of 9.9 months when treated with the standard of care regimen (azacitidine and venetoclax). Aims: We evaluated the safety and efficacy of the triple combination of Quizartinib (Quiz), Venetoclax (VEN), and decitabine (DAC) in pts with relapsed/refractory (R/R) or newly diagnosed FLT3-ITDm AML. Methods: The study included a frontline cohort of pts ineligible for IC and an R/R cohort of pts who had received ≤ 5 prior treatments for AML (up to salvage 5). On Day 14, all pts underwent bone marrow (BM) evaluation, and VEN (400 mg/day or equivalent with azole) was discontinued on Day 14 for pts with BM blasts ≤ 5% (or marrow aplasia/hypocellularity). Pts with Day 14 BM blast &amp;gt;5% continued VEN for 21 days during cycle 1, followed by administration from days 1 to 14 in subsequent cycles, with further dose reductions based on count recovery. All pts received 10 days of DAC (20 mg/m2) for induction, followed by 5-day DAC in subsequent cycles. Quiz (30 or 40 mg/day) was continuously administered daily. Results: A total of 50 pts were enrolled, including 40 R/R and 10 newly FLT3-ITD mutated AML pts (Table 1). Among the 40 R/R AML pts (median 3 [range 1-5] prior AML therapies), 85% had received ≥1 prior FLT3 inhibitors (FLT3i's), with 78% having prior exposure to gilteritinib, and 40% having undergone prior allogeneic stem cell transplantation (ASCT). The rates of CRc, CR+CRi, measurable residual disease (MRD) negativity by multicolor flow cytometry (MFC, sensitivity 10 -4), and FLT3-PCR (sensitivity 10 -2 - 10 -3) negativity among the 40 R/R pts were 68%, 33%, 29% (7/24), and 36% (8/22), respectively (Table 2). The median number of cycles required to achieve a response was 1 (range 1-2). The 60-day mortality rate was 0%. With a median follow-up of 33 months, the median OS was 7.1 months, and the 1-year OS rate was 22% in this predominantly gilteritinib-exposed R/R cohort. Among the 31/40 prior gilteritinib exposed pts the CRc, CR+CRi, median OS and 1-year survival were 65%, 23%, 6.9 month, and 21%. Among the 9/10 prior gilteritinib naïve pts the CRc, CR+CRi, median OS and 1-year survival were 77%, 66%, 10.3 months and 25%. Among the newly diagnosed AML, all achieved CRc (7 CR, 3 CRi), with 9/10 (90%) and 7/9 (78%) evaluable responders being FLT3-PCR and MFC negative, respectively. All 10 pts achieved BM &amp;lt;5% or aplasia/hypocellularity on C1D14. With a median follow-up of 15 months, the median OS was not reached. No pts experienced dose-limiting toxicity (DLT) with Quiz 30 mg/day; however, with Quiz 40 mg/day, the first 2 pts treated developed hematologic DLT (grade 4 neutropenia with a &amp;lt;5% cellular bone marrow with no residual AML lasting ≥42 days). Consequently, Quiz 30 mg/day was declared the RP2D for this combination. In the R/R cohort, grade ≥3 non-hematologic toxicities regardless of attribution, occurring in &amp;gt;10% of pts, included pneumonia (73%), neutropenic fever (53%), sepsis (18%), bacteremia (15%), other infections involving the skin (18%), and gastrointestinal tract (13%). The incidence of grade ≥3 non-hematologic toxicities was less frequent in the frontline cohort, with pneumonia (40%), neutropenic fever (50%), sepsis (10%), bacteremia (20%), and no grade 3 QTcF prolongations observed. The median recovery times for absolute neutrophil count (ANC &amp;gt; 500/μL) and platelet (&amp;gt;50 x 109/L) were 43 days [13-138] and 49 days [21-67] for the R/R cohort, and 40 days [28-56] and 40 days [22-46] for the frontline cohort, respectively. In the frontline cohort, at the last follow-up, 7 pts were in complete remission (CR), 2 ps died with relapsed AML, and 1 pt died in remission postASCT. Among the 40 pts in the R/R cohort, 9 were still alive (7 in CR, 2 with relapsed disease), while 31 pts died (5 deaths in CR, 26 due to relapsed/refractory leukemia). Conclusion: The combination of DAC + VEN + Quiz demonstrated activity in heavily pretreated and prior FLT3i-exposed (including 78% with prior gilteritinib exposure) R/R FLT3-ITDm pts, with a CRc rate of 68% and a median OS of 7.1 months. In the frontline setting, all pts achieved CRc with no early mortality, median count recovery of 40 days, and median OS not reached. The study continues to accrue, and updated results will be reported at the meeting.

Uptake of palliative care services in patients with non-small cell lung cancer receiving immune checkpoint inhibitor therapy: The Mayo Clinic Florida experience.

269 Background: There are strong data showing that patients (pts) with metastatic non-small cell lung cancer (NSCLC) receiving chemotherapy experience better quality of life (QOL) and longer overall survival (OS) when palliative care (PC) services are integrated early in their treatment course. Therefore, at our cancer center, pts with stage IV NSCLC have been referred to PC by oncology providers. In this study, we evaluated the uptake of PC services, specifically in pts with NSCLC who received immune checkpoint inhibitors (ICIs). ICIs have been considered to have less severe or less frequent adverse effects as compared to chemotherapy, possibly leading to fewer referrals to PC. Methods: We conducted a retrospective review of all pts at the Mayo Clinic Cancer Center in Florida who received single-agent ICI therapy for the treatment of stage IV NSCLC at any point between July 1, 2015, and July 1, 2022. The primary aim was to evaluate the uptake of PC services before or during treatment with ICIs. Descriptive statistics were used to characterize pt demographics and outcomes. Results: 129 pts were identified. 53.4% were male, and 46.6% were female. The majority of pts (84.4%) were white. 62 pts (48.0%) were seen by a PC provider before or during ICI treatment; 41 of these (31.7%) were seen by PC after starting ICI therapy. When grouped by year of ICI initiation, 30/73 pts (41.0%) treated between 2015 and June 2018 were seen by a PC provider, as compared to 15/31 pts (48.3%) treated between July 2018 and June 2020 and 17/25 pts (68.0%) treated between July 2020 and July 2022. Interestingly, the majority of pts who received PC services in the 2020-2022 group (12/17, or 70.5%) were seen by a PC provider for the first time prior to ICI initiation, whereas the majority of pts who received PC services prior to July 2020 (37/45, or 82.2%) were seen by a PC provider for the first time after ICI initiation. The mean number of PC visits increased from 1.59 in the 2015-2018 group to 1.84 in the 2018-2020 group and 4.96 in the 2020-2022 group. Conclusions: Uptake of PC services in pts with stage IV NSCLC receiving single-agent ICIs at our cancer center has increased over time, which is encouraging. Nevertheless, the numbers remain suboptimal, with less than 70% of pts receiving PC services. We plan to develop a multidisciplinary quality improvement project involving implementation of a mechanism to ensure that most patients with stage IV NSCLC, regardless of the type of systemic treatment they receive, are receiving PC services.