High Toxicity Rates Research Articles

Tolerability of perioperative chemotherapy for gastric cancer in real clinical practice

Background. The choice of the optimal scheme of perioperative chemotherapy of locally advanced gastric cancer is an urgent problem in real clinical practice. Aim. To analyze therapy tolerability in this cohort of patients. Materials and methods. Perioperative chemotherapy of gastric cancer was performed in 90 patients in the Chemotherapy Department of the Oncology Center №1 of the Yudin City Clinical Hospital from January 2021 to February 2024. Results. The incidence of severe complications at the preoperative stage was 41.9% for the FOLFOX regimen and 40.7% for the FLOT regimen, at the adjuvant stage – 17.4 and 43.2%, respectively. Operative treatment was successfully performed in 79 (87.8%) patients, and the full scope of combined treatment of locally advanced gastric cancer was completed in 59 (65%) patients. 80.8% of pathomorphologic responses in the FOLFOX group and 67.9% in the FLOT group were TRG3-4, with complete response noted in only one patient. Conclusion. High toxicity rates in elderly and comorbid patients on the FOLFOX regimen require the development of an individualized approach to the treatment of this group of patients.

Evaluating Fitness in Older Acute Myeloid Leukemia Patients: Balancing Therapy and Treatment Risks.

Assessing the suitability of older adults with acute myeloid leukemia (AML) for intensive chemotherapy or stem cell transplantation remains a long-standing challenge. Geriatric assessment, which involves the evaluation of multiple dimensions of health, may influence a patient's ability to tolerate intensive or mild-intensity approaches, including treatment-related mortality. Prospective studies are required to validate different fitness criteria, in addition to making it possible to compare the effectiveness of geriatric assessment-based fitness against other criteria, in order to identify which aspects of geriatric assessment are linked to treatment tolerance. It is hoped that validation studies will include different groups of patients receiving either intensive or lower-intensity chemotherapy. At a minimum, geriatric assessment should involve the measurement of the comorbidity burden, cognition, physical function, and emotional health-factors previously associated with mortality in AML. These assessments should be conducted before starting chemotherapy in order to minimize the treatment's impact on the results. While treatment tolerance has traditionally been evaluated through toxicity rates in solid tumor patients, AML treatment often results in high toxicity rates regardless of the intensity. Therefore, early mortality should be the primary endpoint for assessing treatment tolerance, given its significant and clear implications. Other important endpoints might include declines in functional status and quality of life and treatment adjustments or discontinuation due to toxicity. Validating these fitness criteria is essential for guiding treatment choices, improving supportive care, determining trial eligibility, interpreting study outcomes, and informing drug labeling.

Dose escalation with stereotactic body radiotherapy for cervical cancer treatment

BackgroundDose escalation with brachytherapy after pelvic irradiation is standard for treating cervical cancer. Its application can be impossible for some patients. Dose escalation with SBRT is widely used with high local control and acceptable toxicity rates in different body parts. The study enrolled patients who underwent SBRT treatment for dose escalation in the cervix.MethodsPatients who were pathologically diagnosed and treated with cervical SBRT after definitive CRT were included in the study. A total of 30 Gy in 5 fractions for the high-risk volume was prescribed. The first response evaluation was performed three months after the completion of treatment. Treatment toxicity was documented according to the RTOG-EORTC scale. Oncological outcomes and toxicity were assessed.ResultsBetween 02.2019 and 05.2023, 40 patients were treated with an SBRT boost after pelvic irradiation. The median follow-up time was 16 months (7–44 months). The median HR CTV was 47 cc (8,3-168,2 cc). There were 39 patients who achieved a complete response and one who achieved a partial response in the third month after treatment. There were two local or two regional recurrences. The 1-year metastasis-free survival was 88%, and the 1-year progression-free survival was 88%. During the follow-up period, one grade 3 gastrointestinal side effect was observed.ConclusionsSBRT which has low toxicity and reasonable locoregional control rates in a short follow-up period, may be an option for dose escalation in brachytherapy-ineligible cervical cancer patients.

Association between food insecurity, financial toxicity, and healthcare utilization in adolescents and young adults with cancer.

305 Background: Adolescents and young adults with cancer experience high rates of financial toxicity (FT) and unmet health-related social needs (HRSN: food, housing, transportation insecurity). FT and unmet HRSN, specifically FI, are modifiable factors that impact health outcomes; however, the relationship between FI, FT, and healthcare utilization (emergency department (ED) visits or hospitalizations) remains unclear. Leveraging systematic screening for FT and HRSN using the electronic health record (EHR) patient portal among AYAs with cancer, we examined the association between FI, FT, and healthcare utilization measures among AYAs with cancer. Methods: AYAs (ages 15-39) who utilize the EHR patient portal were prompted to complete an 8-item standardized HRSN survey (i.e., food insecurity, housing instability, transportation difficulties) and a 2-item previously established FT survey during e-check in between November 2022 and April 2024. ED visits and hospitalizations were extracted from the EHR directly. Descriptive statistics and associations using chi-square tests were used to describe the patients and examine associations between FI or FT and ED visits or hospitalizations. Results: Of 691 AYAs who completed the HRSN survey, 16% (n=109) screened positive for FI. Among AYAs with FI, 42% (n=46) had at least one ED visit compared with 28% (n=163) among AYAs without FI (p<0.01). Among AYAs with FI, 39% (n=43) were hospitalized at least once compared to 31% (n=179) among AYAs without FI (p=0.07). Of 439 AYAs who responded to the FT survey, 66% (n=290) met criteria for high FT. Within this group, 26% (n=74) had at least one ED visit compared with 17% (n=26) who screened negative (p=0.06). Among AYAs with high FT, 22% (n=65) were hospitalized at least once, compared with 19% (n=28) among those with low or moderate FT (p=0.38). Among 384 AYAs who responded to both the HRSN and FT surveys, 19% (n=74) screened positive for FI, 92% (n=68) of whom also had high financial toxicity. The table describes characteristics of screened AYAs by language and race/ethnicity. Conclusions: FI may be a risk factor for increased ED visits during cancer treatment among AYAs. Systematic screening to identify FI, FT, and other HRSN is important to facilitate referral for resources, support services, or interventions. Sociodemographic characteristics of AYA participants in FI and FT screening. Characteristic +FI -FI +FT -FT N=109 (%) N=582 (5) p-value N=290 (%) N=149 (%) p-value Language <0.01 <0.01 English 82 (75) 496 (85) 241 (83) 134 (90) Spanish 24 (22) 45 (8) 29 (10) 1(1) Other 3 (3) 41 (7) 20 (7) 14 (9) Race/Ethnicity <0.01 <0.01 Hispanic, any race 67 (61) 175 (30) 125 (43) 16 (11) Non-Hispanic Black 12 (11) 62 (11) 30 (10) 10 (7) Non-Hispanic White 16 (15) 219 (38) 78 (27) 84 (56) Other 14 (13) 126 (22) 57 (20) 39 (26)

Patient engagement in a community-partnered hybrid health-related social needs navigation intervention for adolescents and young adults with cancer (AYA-NAV).

173 Background: Adolescent and young adult (AYAs) cancer survivors experience high rates of financial toxicity (FT), which is associated with poorer health outcomes. FT may disproportionately affect AYAs with unmet health-related social needs (HRSN), such as food or housing insecurity. Needs navigation may be an effective intervention to reduce financial distress, however, engagement has been a challenge in prior adult-directed interventions. We hypothesize that a hybrid navigation delivery model with community organization support and digital delivery will reduce financial distress and improve health outcomes. In a pilot study of AYA-NAV, an AYA-directed needs navigation intervention, we report patient engagement among participants. Methods: Eligible AYAs were 15-39 years old, Spanish- or English-speaking, receiving curative-intent treatment for cancer, and screened positive for FT (Comprehensive Score of Financial Toxicity < 22) or unmet HRSN (food, housing, transportation, or utilities insecurity). Participants were referred for a consultation with the Patient Advocate Foundation (PAF), a national organization that provides case management and navigation support for people facing life limiting illness. At month 1, participants were referred to findhelp.org, a digital platform of comprehensive resources to facilitate resolution of unmet HRSN. Monthly check-ins were conducted by the study team to assess acceptability, intervention fidelity, and provide additional navigation support. We plan to enroll 30 participants on this study. Results: Of 19 AYAs that completed screening to date, 13 met criteria for FT or unmet HRSN; 13 (100%) agreed to AYA-NAV participation. To date, of 46 check-ins initiated by the study team, 33 (72%) were completed. All AYAs connected with the study team at least once during the 6-month duration of the study by text, phone, and/or in-clinic. Ten out of 13 (77%) participants reported that they spoke with a PAF case manager, and 7 (70%) of those said it was helpful. If the patient was unable to connect with PAF, more than half (55%) requested to be reconnected during a monthly check-in. Eight of the 13 (62%) participants visited findhelp.org; 6 (75%) of those found the digital platform to be helpful. Most patients referenced the high usability of findhelp.org, and 55% stated they connected to community resources via findhelp.org. Patients qualitatively reported challenges to intervention participation including medical complications, scheduling conflicts, and work commitments. Conclusions: Preliminary data demonstrate high patient engagement and intervention fidelity during a pilot feasibility study of AYA-NAV. Flexible modes for data collection and intervention delivery are important to inclusion of and retention of AYAs in hybrid navigation delivery models. Clinical trial information: NCT06072833 .

Weathering the storm when the end of the road is near: A qualitative analysis of supportive care needs during CAR T-cell therapy in pediatrics.

Chimeric antigen receptor (CAR) T-cell therapy provides promising outcomes in relapsed/refractory B acute lymphoblastic leukemia (ALL), yet still carries high toxicity rates and relatively poor long-term survival. Efficacy has yet to be demonstrated in other diagnoses while toxicity and risk profiles remain formidable. To date, treatment-related symptom burden is gleaned from clinical trial toxicity reports; the patient perspective remains understudied. English- or Spanish-speaking patients (ages 8-25years) undergoing CAR T-cell therapy for any malignancy and their primary caregivers were recruited from Seattle Children's Hospital (SCH), St. Jude Children's Research Hospital (SJCRH), and the Pediatric Oncology Branch of the National Cancer Institute (NCI). Both patient and caregiver completed semi-structured dyadic interviews 3months post treatment. We used directed content analysis for codebook development and thematic network analysis for inductive qualitative analysis. Twenty families completed interviews (13 patients, 15 parents). Patients were a median age 16.5years, predominantly female (65%), White (75%), and diagnosed with ALL (75%). Global themes included "A clear decision," "Coping with symptoms," and "Unforeseen psychosocial challenges." When families were asked to describe the "most challenging part of treatment," most described "the unknown." Most reported "the symptoms really weren't that bad," even among patients hospitalized for severe toxicity events. Fatigue, pain, and nausea were the most prevalent symptoms. Importantly, only one family would have chosen a different therapy, if given another opportunity. Although physical symptoms were largely tolerable, recognizing supportive care opportunities remains imperative, particularly psychosocial concerns.

Dual β-lactams for the treatment of Mycobacterium abscessus: a review of the evidence and a call to act against an antibiotic nightmare.

Mycobacterium abscessus complex is a group of rapidly growing non-tuberculous mycobacteria (NTM), increasingly emerging as opportunistic pathogens. Current treatment options for these microorganisms are limited and associated with a high rate of treatment failure, toxicity and recurrence. In search of new therapeutic strategies, interest has grown in dual β-lactam (DBL) therapy, as research recently discovered that M. abscessus cell wall synthesis is mainly regulated by two types of enzymes (d,d-transpeptidases and l,d-transpeptidases) differently susceptible to inhibition by distinct β-lactams. In vitro studies testing several DBL combinations have shown synergy in extracellular broth cultures as well as in the intracellular setting: cefoxitin/imipenem, ceftaroline/imipenem, ceftazidime/ceftaroline and ceftazidime/imipenem. The addition of specific β-lactamase inhibitors (BLIs) targeting M. abscessus β-lactamase did not significantly enhance the activity of DBL combinations. However, in vivo data are lacking. We reviewed the literature on DBL/DBL-BLI-based therapies for M. abscessus infections to raise greater attention on this promising yet overlooked treatment option and to guide future preclinical and clinical studies.

Recent progress in lanthanide-based fluorescent nanomaterials for tetracycline detection and removal.

Tetracycline (TC) has been widely used in clinical medicine and animal growth promotion due to its broad-spectrum antibacterial properties and affordable prices. Unfortunately, the high toxicity and difficult degradation rate of TC molecules make them easy to accumulate in the environment, which breaks the ecological balance and seriously threatens human health. Rapid and accurate detection of TC residue levels is important for ensuring water quality and food safety. Recently, fluorescence detection technology of TC residues has developed rapidly. Lanthanide nanomaterials, based on the high luminescence properties of lanthanide ions and the high matching with TC energy levels, are favored in the real-time trace detection of TC due to their advantages of high sensitivity, rapidity, and high selectivity. Therefore, they are considered potential substitutes for traditional detection methods. This review summarizes the synthesis strategy, TC response mechanism, removal mechanism, and applications in intelligent sensing. Finally, the development of lanthanide nanomaterials for TC fluorescence detection and removal is reasonably summarized and prospected. This review provides a reference for the establishment of a method for the accurate determination of TC content in complex food matrices.

Prostate-Specific Membrane Antigen PET/CT-Guided, Metastasis-Directed Radiotherapy for Oligometastatic Castration-Resistant Prostate Cancer.

Systemic treatments for metastatic castration-resistant prostate cancer (mCRPC) include androgen deprivation therapy, androgen receptor pathway inhibitors, chemotherapy, and radiopharmaceuticals, all of which have associated toxicity. Prostate-specific membrane antigen (PSMA) PET/CT allows for higher sensitivity in detecting metastatic disease than is possible with conventional imaging. We hypothesized that PSMA PET/CT-guided, metastasis-directed radiotherapy may offer durable disease control with low toxicity rates in patients with mCRPC who have a limited number of metastases. Methods: We retrospectively screened 5 prospective PSMA PET/CT studies for patients with mCRPC who had up to 5 sites of oligorecurrent or oligoprogressive disease on PSMA PET/CT and subsequently received definitive-intent, metastasis-directed radiotherapy to all new or progressing sites with concurrent androgen deprivation therapy. Progression-free survival, freedom from new lines of systemic therapy, and overall survival (OS) were calculated from the start of metastasis-directed radiotherapy using Kaplan-Meier analysis. Biochemical response was defined as at least a 50% decrease in prostate-specific antigen 6 mo after the start of treatment. Toxicity was graded using the Common Terminology Criteria for Adverse Events, version 5. Results: Twenty-four patients met the inclusion criteria with a median follow-up of 33.8 mo (interquartile range, 27.6-45.1 mo). Between October 2017 and April 2023, 11 patients (45.8%) had 1 treated site, 10 patients (41.7%) had 2, and 3 patients (12.5%) had 3. Five sites were prostate or prostate bed, 15 were nodal, 19 were osseous, and 1 was visceral. Seventeen patients (70.8%) continued their preexisting systemic therapy, whereas 7 (29.2%) started a new systemic therapy. Median progression-free survival was 16.4 mo (95% CI, 9.8-23.0 mo). The biochemical response rate was 66.7%. Median freedom from a new line of systemic therapy was 29.0 mo (95% CI, 7.6-50.4 mo). Median OS was not reached. The 2- and 4-y OS rates were 91.1% (95% CI, 79.3%-100%) and 68.8% (95% CI, 45.1%-92.5%), respectively. Grade 2 and grade 3 or higher toxicity rates were 4.2% and 0%, respectively. Conclusion: PSMA PET/CT-guided, metastasis-directed radiotherapy appears to offer durable disease control with low toxicity rates for oligometastatic castration-resistant prostate cancer. Further prospective studies are needed to compare metastasis-directed radiotherapy with systemic therapy versus systemic therapy alone and PSMA PET/CT-guided versus conventional imaging-guided radiotherapy.

Clinical stage IIA/B seminoma - to do or not to do: the role of retroperitoneal lymphadenectomy

About 10% of patients with seminomatous testicuar germ cell tumors are diagnosed with clinical stage II/B. The current guideline recommended treatment options include systemic chemotherapy with 3 cycles PEB or radiation therapy with 30 Gy for CS IIA and 36 Gy for CS IIB. Despite a high cure rate of 90-94% and 82-90% for CS IIA and CS IIB, respectively, both options are associated with a high rate of treatment-associated long-term toxicities. A significantly increased risk for the development of secondary malignancies, cardiovascular and metabolic disease as well as an increased for treatment-associated mortality has been proven in various studies. Primary nerve sparing retroperitoneal lymph node dissection (nsRPLND) has been evaluated in 5 prospective and retrospective clinical studies and it has emerged as a valid treatment alternative. The relapse-rate after a median follow-up of 25-33 months is in the range of 11-30%, so that 70-90% of patients are cured without being subjected to chemotherapy and potential long-term toxicities. All relapsing patients have been cured with secondary salvage chemotherapy. The frequency of significant surgery-associated complications is low with 3-13%. Therapeutic success depends on the surgical experience of the various surgeons and the chosen template, so that this type of surgical interventions should only be performed in centres of excellence with dedicated surgeons. Preoperative evaluation of the new biomarker miR371 has been shown to predict the presence of metastatic disease with an accuracy of around 100% so that this marker might be used in daily routine prior to active treatment in CS IIA/B seminomas.

Effectiveness and feasibility of selective intra-arterial low dose of cisplatin infusion and concomitant radiotherapy for patients with advanced laryngeal cancer with impaired renal function: A retrospective cohort study.

Chemoradiation therapy with high-dose cisplatin is the standard regimen against advanced squamous cell carcinoma of the larynx (SCC-L). However, patients with renal dysfunction are ineligible for this regimen. We investigated the effectiveness and feasibility of selective intra-arterial low-dose cisplatin infusion and radiotherapy (modified [m]-RADPLAT) for patients with impaired renal function. We retrospectively reviewed the data of 77 patients with SCC-L who received m-RADPLAT. Fourteen and 63 patients had creatinine clearance (CrCl) values of 30 ≤ CrCl < 60 mL/min and ≥60 mL/min, respectively. The m-RADPLAT regimen led to no significant changes in serum creatinine or CrCl values post-treatment. The 5-year local control, overall survival, and laryngectomy-free survival rates of the CrCl < 60 and ≥60 groups were 90.0% and 90.5%, 100% and 81.8%, and 100% and 79.0%, respectively. Grade 3 or higher toxicity rates were not significantly different between the groups. The m-RADPLAT regimen yielded favorable survival rates and clinical outcomes in patients with impaired renal function.

NMR-Based Metabolomics of Blood Serum in Predicting Response to Induction Chemotherapy in Head and Neck Cancer-A Preliminary Approach.

The role of induction chemotherapy (iCHT) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is still to be established due to high toxicity and variable response rates. The aim of this retrospective study is to use NMR-based serum metabolomics to predict the response rates to iCHT from the pretreatment samples. The studied group consisted of 46 LA-HNSCC patients treated with iCHT. The response to the treatment was evaluated by the clinical, fiberoptic, and radiological examinations made before and after iCHT. The proton nuclear magnetic resonance (1H NMR) serum spectra of the samples collected before iCHT were acquired with a 400 MHz spectrometer and were analyzed using multivariate and univariate statistical methods. A significant multivariate model was obtained only for the male patients. The treatment-responsive men with >75% primary tumor regression after iCHT showed pretreatment elevated levels of isoleucine, alanine, glycine, tyrosine, N-acetylcysteine, and the lipid compounds, as well as decreased levels of acetate, glutamate, formate, and ketone bodies compared to those who did not respond (regression of the primary tumor <75%). The results indicate that the nutritional status, capacity of the immune system, and the efficiency of metabolism related to protein synthesis may be prognostic factors for the response to induction chemotherapy in male HNSCC patients. However, larger studies are required that would validate the findings and could contribute to the development of more personalized treatment protocols for HNSCC patients.

Percutaneous liver-directed therapies of intrahepatic cholangiocarcinoma.

Cholangiocarcinoma is a hepatobiliary malignancy which can manifest anywhere along the biliary tree. Intrahepatic cholangiocarcinoma occurs in the liver within or beyond the second order bile ducts. The prognosis for patients with intrahepatic cholangiocarcinoma is poor, even when successfully resected there is a very high rate of local recurrence. The available systemic therapies are currently limited and have high rates of toxicity. Percutaneous and transarterial liver-directed therapies can be used to treat intrahepatic cholangiocarcinoma with results comparable to current standard of care systemic therapies in some circumstances. This manuscript will review these the techniques and efficacy of percutaneous and transarterial liver-directed therapies for intrahepatic cholangiocarcinoma.

Overall survival after isolated hepatic perfusion in combination with ipilimumab and nivolumab in patients with uveal melanoma metastases (the SCANDIUM II trial).

9533 Background: Uveal melanoma (UM) is a rare disease, that commonly metastases to the liver metastases and has a very poor prognosis. In patients with metastatic UM to the liver, a one-time treatment with isolated hepatic perfusion (IHP) with high dose melphalan has shown response rates of 40%, while immune checkpoint blockade with ipilimumab (3 mg/kg) in combination with nivolumab (1 mg/kg) (IPI3/NIVO1) has shown response rates of 11-18%. The impact of these treatments on overall survival (OS), if combined, is unclear. In the SCANDIUM II trial, we investigated the safety and tolerability of combination of IHP and IPI3/NIVO1. Methods: In this multicenter open, randomized, controlled, phase Ib trial, patients with liver dominant metastatic uveal melanoma were randomized to receive either IHP followed by combination immunotherapy (four cycles IPI3/NIVO1) (Arm A) or one cycle of IPI3/NIVO1 before IHP followed by three cycles IPI3/NIVO1 (Arm B). Thereafter, patients in both Arm A and B received monotherapy with nivolumab (480 mg q4w) for up to 1 year. Isolated hepatic perfusion was performed using melphalan 1mg/kg perfused through the liver for 60 minutes under hyperthermia (40°C). The primary endpoint was incidence and severity of adverse events. Results: In total, 18 patients were included in the trial, 9 randomized to Arm A and 9 to Arm B. 78% were treatment naïve; 28% had both hepatic and extra-hepatic metastases. Three patients did not undergo IHP as planned, one in arm A and two in arm B. Patients received a mean of 2.4 cycles of IPI/NIVO in Arm A and 3.0 cycles in Arm B. There were more IPI/NIVO related adverse events (grade I-IV) in arm B (48 vs. 86). The overall response rate was 38%, 57% in arm A and 22% in arm B, and the median duration of response was 11.9 months (95% CI, 8.2-NE, n = 6). At a minimum follow-up of 18 months, the overall survival rate was 50% (95% CI, 31.5-79.4%) in the whole study population, 56% (95% CI, 31-99%) in arm A and 44% (95% CI, 21-92%) in arm B. The median OS in arm A was 18.2 months (95% CI, 13.2-NA months) and 17.2 months (95% CI, 14.0-NA months) in arm B. The primary endpoint of adverse events has been reported previously. Conclusions: In patients with liver dominant metastatic uveal melanoma, combining IHP with IPI3/NIVO1 is a feasible treatment. One dose of IPI3/NIVO1 before IHP had no obvious benefit in response or OS, but was associated with higher rates of toxicity. There was no apparent survival advantage compared to patients in the SCANDIUM trial with IHP only, however, sample size and non-overlapping patient characteristics severely hamper comparison between the trials. The numerically higher response rate in Arm A warrants a larger randomized study that is designed to detect a difference between IPI/NIVO with or without IHP. Clinical trial information: NCT01785316 .

The association between age, toxicity and outcomes of abemaciclib treatment in HR+/HER2- metastatic breast cancer.

e13062 Background: The efficacy and safety of abemaciclib in patients (pts) with HR+/HER2− metastatic breast cancer (MBC) was demonstrated in the MONARCH clinical trials; however, real-world evidence is lacking, particularly in elderly pts. The dose reduction strategy used in the MONARCH trials has been shown to be an effective way of managing toxicity without compromising survival. Here, we provide real-world data on the efficacy and safety of abemaciclib treatment, focusing also on elderly pts with HR+/HER2− MBC and the association between abemaciclib dose reduction and survival. Methods: The efficacy and safety of abemaciclib in patients (pts) with HR+/HER2− metastatic breast cancer (MBC) was demonstrated in the MONARCH clinical trials; however, real-world evidence is lacking, particularly in elderly pts. The dose reduction strategy used in the MONARCH trials has been shown to be an effective way of managing toxicity without compromising survival. Here, we provide real-world data on the efficacy and safety of abemaciclib treatment, focusing also on elderly pts with HR+/HER2− MBC and the association between abemaciclib dose reduction and survival. Results: The median age of 134 pts was 62 yrs (IQR, 54-71), with 40 pts (29.9%) older than 70 yrs. Median rwPFS (mrwPFS) with abemaciclib + endocrine therapy in the ≥70 vs &lt;70 age group was 15 vs 17 months (HR:1.1, 95% CI 0.70-1.76; p=0.65) and median OS (mOS) was 25 vs 34 months (HR:1.4, 95% CI 0.82-2.39, p=0.21). The most common rwAEs are shown (Table). Abemaciclib dose reductions occurred in 40% of pts ≥70 yrs of age compared to 28% of younger pts (χ2 (1)=1.98; p=0.22). There was no difference in mrwPFS between pts who had a dose reduction and those who did not (mrwPFS 15 vs 17 months (HR: 1.03, 95% CI 0.65-1.63, p=0.91) and mOS 28 vs 30 months (HR: 1.16, 95% CI 0.68-1.99; p=0.58)). Conclusions: The results of our study support the efficacy and safety of abemaciclib treatment in pts with HR+/HER2- MBC in real-world clinical practice. Age did not appear to be an important factor associated with higher rates of toxicity and similar efficacy of abemaciclib was demonstrated in the elderly pts population compared to younger pts. Importantly, abemaciclib dose reductions did not compromise survival. Clinical trial information: ERIDNPVO-0060/2022. [Table: see text]

Effectiveness and toxicity of multidisciplinary treatment of head and neck cancer among people with HIV: Real-world evidence from a tertiary cancer center in Brazil.

e24139 Background: The incidence of head and neck squamous cell carcinoma (HNSCC) is rising among people with HIV (PWH). Previous studies have shown an increase in treatment-related toxicities in this population. This study aims to determine the demographics and treatment outcomes in this patient group at a tertiary cancer center in Brazil. Methods: HNSCC patients (pts) with HIV diagnosis treated at our institution between 2009 and 2022 were included. Medical charts were analyzed to extract clinical data. Log rank was used to compare survival estimates and stratified Cox regression model was used for univariate and multivariate analyses. Results: Our search identified 75 pts with HIV among 5956 pts with HNSCC. Median age at cancer diagnosis was 53 years (IQR 49-59.5), 80% were male and 82.7% had a smoking history. Most pts had an oropharynx primary tumor (38.7%) and locally advanced disease (80%), with T3 and T4 tumors in 55 pts (73.3%) and N+ in 48 pts (64.1%). A feeding tube (FT) was placed in 32% of pts before treatment. HIV viral load was detectable in 23 (30.7%) pts and 19 (25.3%) had a CD4 count of fewer than 200 cells/mm³, while 97.3% of the pts were on combination antiretroviral therapy at the time of HNSCC diagnosis. 26 pts were operated with curative intent and 20 pts received adjuvant therapy. In the total population, concurrent cisplatin-based chemoradiation (CCRT) was prescribed to 26 pts (34.7%) and 34 (45.3%) received radiotherapy (RT) alone. 65.4% of the pts in the CCRT group and 20.6% in the RT group were unable to complete treatment as prescribed, mostly due to toxicity. No pts with positive viral load or CD4 &lt; 200 cells/mm³ were able to complete CCRT. Treatment toxicity led to hospitalization in 24% of pts and 7 pts needed FT placement. There were 8 deaths during treatment, 5 in pts with CD4 &lt; 200 cells/mm³. Positive viral load was associated with CCRT interruption (p = 0.03) and a CD4 count of less than 200 cells/mm³ increased the risk of death during treatment (p = 0.02). Median overall survival (OS) was 31.7 months (IQR 14.6-53.7). Multivariate analysis did not show a statistically significant decrease in OS in pts with positive viral load or CD4 &lt; 200 cells/mm³. Factors associated with worse OS on multivariate analysis were FT usage (HR = 2.91; 95% CI: 1.45-5.83) and Eastern Cooperative Oncology Group Performance Status (ECOG-PS) greater than 1 (HR = 3.26; 95% CI: 1.46-7.24). Conclusions: HNSCC treatment in PWH is associated with a high discontinuation rate, even in pts with antiviral therapy. High toxicity rates and deaths during treatment were observed. Positive viral load and low CD4 count were considered contributing factors. ECOG-PS and enteral feeding tube usage were independently associated with worse survival. The development of more tailored strategies in this population is needed to improve outcomes in patients with HNSCC and HIV.

Change in financial toxicity during early-phase cancer clinical trial (EP-CT) participation.

11119 Background: The high costs of care (financial toxicity) represent a pressing concern in oncology. Little is known about the financial toxicity experienced by EP-CT participants. We sought to describe changes in financial toxicity during EP-CTs and assess associations of change in toxicity with patient characteristics, additional patient-reported outcomes (PROs), and trial reimbursement structure. Methods: We prospectively enrolled adults participating in EP-CTs from 4/2021 – 1/2023. We administered surveys at baseline (between enrollment and Day 1 of trial) and monthly during trial participation. We assessed financial toxicity using the COST tool, graded as low (≥26) and high (0–25) toxicity. We also surveyed baseline hope (Hope Herth Index), quality of life (QOL; FACT-G) and symptom burden (psychological: PHQ-4; physical: ESAS). We calculated within-patient changes in COST score and conducted linear mixed models, controlling for baseline COST score, to determine associations of change in financial toxicity with patient characteristics, baseline PROs, and trial reimbursement structure (using a factor x time interaction term). Results: Of 221 eligible patients, we enrolled 205 (median age = 63.3 years [range 32.8-88.6], 57.1% female). Most common tumors were GI (34.6%) and breast (20.0%). At trial start, 35.0% of patients reported high financial toxicity, 40.5% at 1 month, 33.6% at 2 months, 25.5% at 6 months, and 40.0% at 1 year. Within-patient COST score worsened over time (B=-0.20, p=0.059), although this change did not reach significance. We found no patient characteristics that significantly correlated with change in COST score, including age (B=-0.005, p=0.602), sex (B=-0.097, p=0.667), GI cancer (B=-0.11, p=0.118), annual income &gt;$60,000 (B=-0.10, p=0.306), and current employment (B=-0.34, p=0.121). Higher baseline QOL was associated with increased COST score (financial wellbeing, while on trial (B=0.012, p=0.011); there was no significant association with other baseline PROs. Most patients (64.4%) enrolled on trials that offered reimbursement for study costs. Of those offering reimbursement, 40.1% had all research-specific costs reimbursed. There was no significant association between change in COST score and presence of any reimbursement (B=0.12, p=0.614) or presence of full reimbursement (B=-0.072, p=0.784). Conclusions: In this cohort of EP-CT participants, over one-third reported high rates of financial toxicity, which appeared relatively stable over time on trial. We did not identify any demographic factors associated with risk of worsening toxicity but did find that high baseline QOL may be protective. Trial reimbursement did not lead to improvement in financial wellbeing. Findings demonstrate that EP-CT participation may not place excess financial burden on at-risk patients and highlight the need to monitor for financial toxicity across all trial participants.

Examining the financial landscape of cancer: An analysis of debt and bankruptcy among patients in Massachusetts (2010-2019).

11032 Background: Financial toxicity is commonly reported by patients following a cancer diagnosis. Prior patient surveys indicate that up to one-third of cancer patients incur medical debt, of which 55% carry balances exceeding $10,000. In addition to debt and bankruptcy, credit scores are an important indicator of socioeconomic well-being following cancer diagnosis, because they affect housing stability, transportation access, and may even be predictive of health. Limited studies quantify incurred debt, bankruptcy rates, or credit scores following a cancer diagnosis compared with patients without a cancer diagnosis. Methods: Individuals with a cancer diagnosis in Massachusetts from 2010 to 2019 were identified through the Massachusetts Cancer Registry, and patient-level records on debt, bankruptcy, and other measures of financial well-being were linked using data from a major United States credit bureau. Changes in medical debt, credit score and bankruptcy filings were evaluated over time and compared with a random sampling of individuals residing in Massachusetts over the same time period that did not have a cancer diagnosis and were matched based on demographic factors. Results: 99,175 individuals with cancer and 188,875 individuals without cancer were identified, and average annual total debt balances were $758 and $669, respectively, throughout the study period. The highest total debt balances were observed among individuals with thyroid cancer ($913). Average annual medical collection balances were $45 for individuals without cancer and $52 among those with cancer with the highest balances among those with liver cancer ($66). Across the study period, the average annual bankruptcy incidence rate per 100 persons was 7.15 for those without cancer and 6.22 among those with cancer, with the highest incidence rates among those with thyroid cancer (7.34). Although there was a gradual increase in credit score in the control population, survivors of bladder, liver, ovarian, colorectal and lung cancers experienced a decline in credit scores. Conclusions: High rates of financial toxicity among individuals with cancer suggest that widespread healthcare and consumer finance reforms have not yet fully alleviated medical debt and bankruptcy in Massachusetts. Further research is needed to understand drivers of financial burden over time among those with cancer.

Ultra‐low dose radiation therapy for primary cutaneous indolent B‐cell lymphomas

AbstractBackgroundPrimary cutaneous follicle centre lymphoma (PCFCL) and primary cutaneous marginal zone lymphoma (PCMZL) are indolent radiosensitive lymphomas, with national guidelines recommending 24 Grey (Gy) in 12 fractions, despite shorter regimens showing no difference in overall survival. Multiple studies demonstrate 4 Gy in two fractions is effective in other indolent lymphomas. Shorter regimens may result in less toxicity for patients.ObjectivesWe aim to characterise local control rates in PCFCL and PCMZL treated with radiation therapy (RT) with 4 Gy in two fractions.MethodsFrom a single institution database, we retrospectively identified all patients with PCFCL and PCMZL treated with 4 Gy in two fractions between 2011 and 2022. Prior topical or systemic treatments were permitted. T‐cell or high‐grade B‐cell cutaneous lymphomas, or those with less than 6 months follow‐up, were excluded. Primary outcomes were rates of response and local failure per lesion as determined by a radiation oncologist and oncologic dermatologist.ResultsForty‐three consecutive patients with 98 lesions treated were identified. Twenty‐four (56%) of the patients had PCMZL, and the remainder had PCFCL. Most lesions (97%) received RT with electrons. The complete response or partial response rate was 94%. Six local failures were identified (6%). With a median follow‐up of 2.75 years, 1‐, 2‐ and 3‐year local failure‐free survival were 94%, 94% and 92%, respectively. There was minimal acute toxicity, no late toxicity and no cosmesis issues. No clinical features were predictive of local failure.ConclusionsUltra‐low dose radiation was associated with high rates of local control and minimal toxicity and may reduce personal burden and financial toxicity in appropriately selected patients.

Deoxynivalenol Induces Intestinal Epithelial Barrier Damage through RhoA/ROCK Pathway-Mediated Apoptosis and F-Actin-Associated Tight Junction Disruption.

Deoxynivalenol (DON) poses a serious global food safety risk due to its high toxicity and contamination rate. It disrupts the intestinal epithelial barrier, allowing exogenous toxins to enter the circulation and resulting in sepsis and systemic toxicity. In this research, 32 male Kunming mice and Porcine Small Intestinal Epithelial (IPEC-J2) cells were treated with DON at 0-4.8 mg/kg (7 d) and 0-12 μM (24 h), respectively. Histopathological results revealed that DON disrupted the intestinal epithelial barrier, causing apoptosis and tight junction (TJ) injury. Immunofluorescence and protein expression results showed that DON-induced p53-dependent mitochondrial pathway apoptosis and fibrillar actin (F-actin)-associated TJ injury and that the RhoA/ROCK pathway were activated in mice jejunal tissue and IPEC-J2 cells. Pretreatment with RhoA or ROCK inhibitors (Rosin or Y-27632) maintained DON-induced apoptosis and F-actin-associated TJ injury in IPEC-J2 cells. Thus, DON induces damage to the intestinal epithelial barrier through the RhoA/ROCK pathway-mediated apoptosis and F-actin-associated TJ disruption.