Concomitant Chemotherapy Research Articles

Results of complex treatment of anaplastic glioma

Anaplastic glioma is a rare disease with an unfavorable prognosis. Currently, guidelines do not provide clear recommendations for the optimal treatment of patients with anaplastic glioma, necessitating the use of individual case series to guide clinical decisionmaking. Therefore, this study aimed to review the clinical management of anaplastic gliomas, including long-term follow-up (catamnesis) and complications. Using a retrospective approach, we analyzed patients with anaplastic glioma who were treated in our institution, either with or without concomitant chemotherapy, from early 2000 until 2021. Overall survival and progressionfree survival were calculated from the time of diagnosis until death and from the initiation of radiation therapy until the detection of disease progression through MRI. Our findings indicate that the combination of surgery, radiotherapy, and chemotherapy yielded the maximum benefit in the treatment of anaplastic glioma. However, managing this aggressive tumor remains challenging, despite continuous advancements in therapeutic options. Optimal management necessitates a multidisciplinary approach and a comprehensive understanding of potential complications arising from both the disease itself and its treatment.

Reduced mouth opening in patients with head and neck cancer treated with radiation therapy: an analysis of the Clinical Registry of Dental Outcomes in Head and Neck Cancer Patients (OraRad)

ObjectivesTrismus/reduced mouth opening (RMO) is a common side effect of radiotherapy (RT) for head and neck cancer (HNC). The objective was to measure RMO, identify risk factors for RMO, and determine its impact on quality of life (QOL). Patients and MethodsOraRad is an observational, prospective multicenter cohort study of patients receiving curative intent RT for HNC. Interincisal mouth opening measurements (n = 565) and patient reported outcomes were recorded before RT and every 6 months for 2 years. Linear mixed-effects models were used to evaluate change in mouth opening and assess the relationship between trismus history and change in QOL measures. ResultsInter-incisal distance decreased from a mean (SE) of 45.1 (0.42) mm at baseline to 42.2 (0.44) at 6-months with slight recovery at 18-months (43.3, 0.46 mm), but no additional improvement by 24-months. The odds of trismus (opening <35mm) were significantly higher at 6 months (OR=2.21, 95% CI: 1.30 to 3.76) and 12 months (OR=1.87, 95% CI: 1.08 to 3.25) compared to baseline. Females were more likely to experience trismus at baseline and during follow up (p<0.01). Patients with oral cavity cancer had highest risk for trismus at baseline and post-RT (p<0.01). RMO was associated with higher RT dose to primary site and receiving concomitant chemotherapy (p<0.01). Trismus was associated with self-reported difficulty opening the mouth and dry mouth (p<0.01). ConclusionsDecrease in mouth opening is a common treatment-related toxicity after RT with some recovery by 18-months. Trismus has a significant impact on survivor QOL. Statement of Clinical RelevanceDecrease in mouth opening is a common treatment related toxicity after RT, which has a significant impact on survivor QOL. Variability in restricted mouth opening after RT is related to specific patient, cancer, or treatment characteristics.

Platinum-Based Chemotherapy Attenuates the Effector Response of CD8 T Cells to Concomitant PD-1 Blockade.

Combination of chemotherapy with programmed cell death 1 (PD-1) blockade is a front-line treatment for lung cancer. However, it remains unknown whether and how chemotherapy affects the response of exhausted CD8 T cells to PD-1 blockade. We used the well-established mouse model of T-cell exhaustion with chronic lymphocytic choriomeningitis virus (LCMV) infection to assess the effect of chemotherapy (cisplatin+pemetrexed) on T-cell response to PD-1 blockade, in the absence of the impact of chemotherapy on antigen release and presentation observed in tumor models. When concomitantly administered with PD-1 blockade, chemotherapy affected the differentiation path of LCMV-specific CD8 T cells from stem-like to transitory effector cells, thereby reducing their expansion and production of IFNγ. After combination treatment, these restrained effector responses resulted in impaired viral control, compared with PD-1 blockade alone. The sequential combination strategy, where PD-1 blockade followed chemotherapy, proved to be superior to the concomitant combination, preserving the proliferative response of exhausted CD8 T cells to PD-1 blockade. Our findings suggest that the stem-like CD8 T cells themselves are relatively unaffected by chemotherapy partly because they are quiescent and maintained by slow self-renewal at the steady state. However, upon the proliferative burst mediated by PD-1 blockade, the accelerated differentiation and self-renewal of stem-like cells may be curbed by concomitant chemotherapy, ultimately resulting in impaired overall CD8 T-cell effector functions. In a translational context, we provide a proof-of-concept to consider optimizing the timing of chemo-immunotherapy strategies for improved CD8 T-cell functions. See related commentary by Vignali and Luke, p. 1705.

Satisfaction with radiotherapy care among cancer patients treated in Germany-secondary analysis of alarge multicenter study.

Patient satisfaction with healthcare has been linked to clinical outcomes and regulatory agencies demand its regular assessment. Therefore, we aimed to investigate patient satisfaction with radiotherapy care and its determinants. This is asecondary analysis of amulticenter prospective cross-sectional study. Eligible cancer patients anonymously completed questionnaires at the end of acourse of radiotherapy. The outcome variable was overall patient satisfaction with radiotherapy care measured with a10-point Likert scaled single-item. Given patient satisfaction was defined for patients scoring ≥ 8points. Determinants of given patient satisfaction were assessed by univariable and multivariable analyses. Ap-value < 0.05 was considered statistically significant. Out of 2341 eligible patients, 1075 participated (participation rate 46%). Data on patient satisfaction was provided by 1054 patients. There was aright-skewed distribution towards more patient satisfaction (mean = 8.8; SD = 1.68). Given patient satisfaction was reported by 85% (899/1054) of the patients. Univariable analyses revealed significant associations of lower patient satisfaction with tumor entity (rectal cancer), concomitant chemotherapy, inpatient care, treating center, lower income, higher costs, and lower quality of life. Rectal cancer as tumor entity, treating center, and higher quality of life remained significant determinants of patient satisfaction in amultivariable logistic regression. Overall patient satisfaction with radiotherapy care was high across 11centers in Germany. Determinants of patient satisfaction were tumor entity, treating center, and quality of life. Although these data are exploratory, they may inform other centers and future efforts to maintain high levels of patient satisfaction with radiotherapy care.

Impact of low skeletal muscle mass in oropharyngeal cancer patients treated with radical chemo-radiotherapy: A mono-institutional experience.

Low skeletal muscle mass index (SMI) has recently emerged as an independent prognostic factor in oncological patients and it is linked with poor survival and higher treatment toxicity. The present study aims to determine the possible impact of low SMI on survival and acute toxicity in oropharyngeal patients. Seventy-six patients with locally advanced oropharyngeal squamous cell carcinoma (stage III-IVC) were treated in our institution with Helical TomoTherapy® (HT - Accuray, Maddison, WI, USA) between 2005 and 2021. All patients received concomitant platinum-based chemotherapy (CT) (at least 200 mg/m2). The SMI was determined using the calculation of cross-sectional area at C3. Twenty patients (26%) presented pre-treatment low SMI, according to Chargi definitions. All patients concluded the treatment. Thirteen patients with low SMI (65%) and 22 patients with normal SMI (39%) presented acute toxicity greater than or equal to grade 3, but this difference was not statistically significant (p-value = 0.25). Overall survival was analyzed in 65 patients, excluding those who finished CT-RT less than six months before the analysis. Overall survival was significantly lower in low SMI versus normal SMI patients (p-value = 0.035). Same difference was observed in N0-N2a patients, suggesting an important role of SMI also in lower nodal burden and putatively better prognosis. Although the results are limited to a small population, our case series has the advantage to be very homogeneous in patients and treatment characteristics. In our setting, SMI demonstrated a crucial impact on overall survival. Further investigation with larger samples is necessary to confirm our results to improve patient outcomes.

CTNI-58. UPDATED RESULTS AND MOLECULAR SUBGROUP ANALYSES FROM THE RANDOMIZED PHASE 3 MIRAGE TRIAL ON MARIZOMIB IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

Abstract BACKGROUND The standard of care for patients with newly diagnosed glioblastoma includes maximum safe resection followed by radiotherapy (RT) with concomitant and maintenance temozolomide (TMZ) chemotherapy (TMZ/RT→TMZ). Among potential new therapeutic strategies, targeting the proteasome has been considered promising because of its implication in numerous biological processes in tumors cells. Marizomib is a novel small molecule proteasome inhibitor that crosses the blood brain barrier and showed signs of activity in recurrent glioblastoma. METHODS EORTC 1709/CCTG CE.8 was a randomized, controlled, multicenter, open label phase 3 superiority trial. Major inclusion criteria were histologically confirmed newly diagnosed glioblastoma, age of 18 years or older and a Karnofsky performance status (KPS) &amp;gt; 70. Patients with tumors known to harbor an isocitrate dehydrogenase mutation were not eligible. RESULTS The trial was opened at 82 institutions in Europe, Canada and the US and 749 patients (of 750 planned) were randomized in a 1:1 ratio. Following a pre-planned interim analysis and a recommendation of the independent data monitoring committee, enrolment was discontinued. No significant difference in the median OS (mOS) was observed (standard arm: 17 months, marizomib arm: 16.5 months; p = 0.64; HR = 1.04). Median PFS was 6.0 vs. 6.3 months (p = 0.67; HR = 0.97). Patients with tumors harboring an unmethylated O6-methylguanine DNA methyltransferase (MGMT) promoter had a mOS of 14.5 months in the standard therapy group and 15.1 months in the marizomib arm (p = 0.27, HR = 1.13). Among patients with an MGMT promoter-methylated tumor, median OS was 29.4 months in the marizomib arm and 25.5 months in the standard arm (p = 0.41, HR = 0.86). More CTCAE grade 3/4 treatment-emergent adverse events were noticed in the marizomib arm than in the standard arm. CONCLUSIONS The addition of marizomib to standard temozolomide-based radiochemotherapy was associated with more toxicity but did not confer a survival benefit in glioblastoma patients, independent of the MGMT promoter methylation status.

CTNI-56. FEASIBILITY AND EFFICACY OF AI-GUIDED PERSONALIZED PRECISION RADIATION THERAPY IN NEWLY DIAGNOSED GLIOBLASTOMA: A MATCHED-CONTROL STUDY

Abstract PURPOSE The aim of this study was to evaluate the feasibility and efficacy of AI-guided personalized precision radiation therapy (PPRT) in improving outcomes for patients with newly diagnosed glioblastoma. METHODS In an open-label trial conducted at the University of Pennsylvania (NCT03477513), between August 2018 and April 2021, 17 patients with IDH-wildtype glioblastoma who underwent maximal safe resection were enrolled. They were matched with a cohort of glioblastoma patients based on age, sex, extent of resection (EOR), O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation status, and IDH status. Propensity Score Matching (PSM) was employed to assess the impact of the intervention on the likelihood of survival, using logistic regression to estimate the propensity score. Four patients were disqualified based on exclusion criteria. The PPRT group received personalized radiation dose escalation guided by AI-based predictive modeling of recurrence, along with concomitant and maintenance temozolomide chemotherapy. The control group received standard-of-care chemoradiotherapy between 2012 and 2020. In this study, we utilized a previously published and evaluated (retrospectively and prospectively) predictive AI model, which accurately estimated neoplastic cell infiltration and predicted future tumor recurrence using preoperative, multi-parametric MRIs. RESULTS Median overall survival was 24.4 months in the PPRT-temozolomide group and 17.9 months in the standard-of-care treatment group (hazard ratio, 0.34; 95% CI: 0.15-0.77; p = 0.009). PPRT was well-tolerated, with low-grade adverse events during radiation. Radiation necrosis occurred in 54% of the PPRT-temozolomide group and 36% of the standard-of-care group. CONCLUSION AI-guided PPRT in newly diagnosed glioblastoma patients demonstrated feasibility in routine clinical practice and led to a statistically significant improvement in overall survival compared to matched controls receiving standard-of-care treatment. These findings highlight the potential of personalized precision radiation therapy, with focused dose escalation, in enhancing outcomes for glioblastoma patients and emphasize the need for prospective validation in a randomized controlled clinical trial.

Clinical Course of Adult T-Cell Leukemia-Lymphoma with Central Nervous System Involvement

Background: Adult T-cell leukemia-lymphoma (ATL) is a peripheral T-cell lymphoma with a highly diverse clinical presentation. Although central nervous system (CNS) involvement is common, the detailed clinical presentation of CNS-ATL needs to be clarified. Objective: This study aims to clarify the clinical course of ATL with CNS involvement. CNS involvement was classified according to the criteria of JALSG202 for acute lymphocytic leukemia as follows: Grade I: no symptoms and cerebrospinal fluid (CSF)cell count less than 5/μl and presence of abnormal lymphocytes; Grade II: asymptomatic and CSF cell count 5-50/μl and presence of abnormal lymphocytes; Grade III: symptomatic or CSF cell counts &amp;gt; 50 cells/μl and presence of abnormal lymphocytes. Results: The analysis included 213 cases of ATL treated at Kagoshima University Hospital from 2002 to 2021. Of these aggressive ATL cases, the clinical subtypes at initial presentation were as follows: acute type 109, lymphoma type 54, chronic type 30, smoldering type 18, and 2 cases were unclassifiable. The median age of the patients was 63 years, and 96 cases (45.1%) were women. Sixty patients had received allogeneic hematopoietic stem cell transplants. During the clinical course, 28 patients (13.1%) with a median age of 61 years and 13 women（46.4%）had CNS involvement. Two cases were classified as Grade I, six as Grade II, and 20 as Grade III. Among them, nine patients (4.2%) showed neurological symptoms at the initial ATL diagnosis, and 1 patient presented with neurological findings at the time of chronic to acute transformation. Of the remaining 203 patients, prophylactic intrathecal chemotherapy was administered in 101 cases, at which time CNS involvement was diagnosed in 9 cases (8.9%). Three patients developed symptomatic involvement while responding to chemotherapy. One patient developed symptomatic involvement when refractory to chemotherapy. Four cases were CNS recurrence with systemic disease progression after remission. Two cases were identified as primary CNS-ATL. The simplified ATL-PI (Prognostic Index) at initial ATL diagnosis for the 28 patients with CNS involvement revealed four cases with high-risk, thirteen with intermediate-risk, two with low-risk, six not eligible due to indolent ATL subtypes, and three cases with unknown risk. The incidence of CNS involvement by ATL subtype was 17.8% (19/107) for acute type, 1.8% (1/54) for lymphoma type, 16.7% (5/30) for chronic type, and 0% for smoldering type (excluding 1 case of unknown subtype and 2 cases of primary CNS-ATL) at ATL diagnosis. At the diagnosis of CNS involvement, 15 (53.6％) patients showed at least 5% of ATL cells in the peripheral blood. During a median observation period of 429 days, the 1-year cumulative incidence of CNS involvement was 12.3% (95% CI 8.3-17.1%). High-dose methotrexate-based therapy was administered to 5 patients with CNS involvement, which had a certain effect on CNS lesions but had limited efficacy for other lesions. All of these cases were treated with concomitant intrathecal chemotherapy. The 2-year overall survival rate after diagnosis of CNS involvement was 16.9% (95% CI 4.9-35.2%). The CNS-IPI (International Prognostic Index) did not predict CNS involvement in ATL. Conclusions: This is the largest study to examine the clinical course of CNS involvement of ATL. The 1-year cumulative incidence of CNS involvement was 12.3%, indicating that CNS involvement is an early complication after diagnosis of aggressive ATL, especially in leukemic subtypes. The prognosis after the diagnosis of CNS involvement was also clarified. The high frequency of CNS involvement during prophylactic intrathecal chemotherapy in patients with ATL without neurological symptoms suggests that it is an important clinical question that needs to be addressed.

Impact of declared wildfire disasters on survival of lung cancer patients undergoing radiation treatment.

302 Background: In recent years, the frequency and severity of climate-driven disasters, including wildfires, have posed significant challenges to the delivery of oncology care. Among various treatment modalities, radiotherapy stands is particularly vulnerable due to its reliance on consistent electrical power and daily treatment sessions. For patients receiving radiation treatment for locally advanced non-small cell lung cancer (NSCLC), even minor disruptions in treatment continuity have been shown to have a detrimental impact on overall survival. Methods: Patients undergoing definitive radiotherapy for nonoperative locally advanced NSCLC between 2004 and 2019 were selected from the hospital-based National Cancer Database, which captures approximately 70% of all cases in the United States. Disaster declarations were identified from the Federal Emergency Management Agency from 2004 to 2019. Exposed patients (n = 1,419) were defined as those who had a wildfire disaster declared in the county of the treatment facility during the exposure window (within 12 weeks of radiotherapy start date), while unexposed patients (n = 226,719) had no disasters declared within the same timeframe. Overall survival was defined as age when radiation therapy started and age of death, last contact, or study end. Cox proportional hazards was used for estimating hazard ratios (HRs) adjusted for sex, region, health insurance, comorbidities, facility type, lymph node involvement and concomitant chemotherapy. Survival estimates were weighted by the inverse of the probability of remaining uncensored at the end of the exposure window. Results: A total of 228,138 individuals were included in the study. Our preliminary data shows that exposed individuals were more likely to receive treatment in facilities located in western states, have no comorbidities, and have private health insurance coverage. Individuals whose facility had a wildfire disaster declared within 12 weeks of the radiation start date had worse overall survival (HR = 1.03; 95% Confidence Interval = 1.01, 1.06) compared to unexposed individuals with sensitivity analyses pending. Conclusions: Our study highlights the vulnerability of individuals undergoing radiotherapy for NSCLC to the hazards posed by wildfires. These findings underscore the urgent need for oncology institutions to prioritize the climate adaptation efforts aimed at safeguarding the needs of this vulnerable population.

Pencil Beam Scanning Proton Therapy for Adolescents and Young Adults with Head and Neck Sarcomas

PurposeTo assess clinical outcomes of adolescents and young adults (AYAs) with head and neck sarcomas (HNSs) treated with pencil beam scanning proton therapy (PBSPT) and to report quality of life (QoL). Materials and MethodsTwenty-eight AYAs (aged 15 to 39 years) with HNS treated between January 2001 and July 2022 at our institution were included. The median age was 21.6 years. Rhabdomyosarcoma (39.3%), Ewing sarcoma (17.9%), chondrosarcoma (14.3%), and osteosarcoma (14.3%) were the most frequent diagnoses. Three (10.7%) patients were metastatic before PBSPT and 13 (46.4%) patients had a tumor with intracranial extension. The median total radiation dose was 63 GyRBE (range, 45 to 74 GyRBE). Thirteen (46.4%) patients received concomitant chemotherapy. Toxicity was reported according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US National Institutes of Health, Bethesda, Maryland). Survival was estimated using the Kaplan-Meier method. QoL was assessed using a PEDQOL (Pediatric Quality of Life Questionnaire) questionnaire. Self-reported outcomes were assessed using institutional questionnaires. ResultsWith a median follow-up of 57 months (range, 3.7 to 243 months), 5 patients (17.8%) had local failure (LF) only, 2 (7.1%) experienced distant failure (DF) only, and 2 (7.1%) had LF and DF. The estimated 5-year local control (LC) and distant control (DC) rates were 71.8% and 80.5%, respectively. The median times to LF and DF were 13.4 and 22.2 months, respectively. Four (14.3%) patients died, all but one from their HNS. Estimated 5-year overall survival was 90.7%. Six (21.4%) patients developed nonocular grade ≥3 toxicity, which consisted of otitis media (n = 2), hearing impairment (n = 2), osteoradionecrosis (n = 1), and sinusitis (n = 1). Four (14.3%) patients developed cataracts that required surgery. The 5-year freedom from nonocular grade 3 toxicity was 91.1%. No grade 4 or higher toxicity was observed. Adolescents rated their quality of life before treatment worse than their parents did. ConclusionExcellent outcomes with acceptable late-toxicity rates were observed for AYAs with HNS after PBSPT.

A Multicenter Evaluation of Different Chemotherapy Regimens in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Chemoradiation

PurposeThe number of older adults with head-and-neck squamous cell carcinoma (HNSCC) is increasing, and treatment of these patients is challenging. Although cisplatin-based chemotherapy concomitantly with radiotherapy is considered standard regimen for patients with locoregionally advanced HNSCC, there is substantial real-world heterogeneity regarding concomitant chemotherapy in older HNSCC patients. MethodsThe XXX study is an international multicenter cohort study including older (≥65 years) HNSCC patients treated with definitive radiotherapy at 13 academic centers in the United States and Europe. Here, patients with concomitant chemoradiation were analyzed regarding overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier analyses, while Fine‐Gray competing risks regressions were performed regarding the incidence of locoregional failures (LRFs) and distant metastases (DMs). ResultsSix hundred ninety-seven patients with a median age of 71 years were included in this analysis. Single-agent cisplatin was the most common chemotherapy regimen (n=310; 44%), followed by cisplatin plus 5-fluorouracil (n=137; 20%), carboplatin (n=73; 10%), and mitomycin c plus 5-fluorouracil (n=64; 9%). Carboplatin-based regimens were associated with diminished PFS (HR=1.39 [1.03-1.89], p<0.05) and a higher incidence of LRFs (SHR=1.54 [1.00-2.38], p=.05) compared with single-agent cisplatin, whereas OS (HR=1.15 [0.80-1.65], p=.46) was comparable. There were no oncological differences between single-agent and multi-agent cisplatin regimens (all p>.05). Median cumulative dose of cisplatin was 180 mg/m2 (IQR, 120-200 mg/m2). Cumulative cisplatin doses ≥200 mg/m2 were associated with increased OS (HR=0.71 [0.53-0.95], p=.02), PFS (HR=0.66 [0.51-0.87], p=.003), and lower incidence of LRFs (SHR=0.50 [0.31-0.80], p=.004). Higher cumulative cisplatin doses remained an independent prognostic variable in the multivariate regression analysis for OS (HR=0.996 [0.993-0.999], p=.009). ConclusionsSingle-agent cisplatin can be considered as the standard chemotherapy regimen for older HNSCC patients who can tolerate cisplatin. Cumulative cisplatin doses are prognostically relevant also in older HNSCC patients. Trial RegistrationXXX

Influence of MRI Follow-Up on Treatment Decisions during Standard Concomitant and Adjuvant Chemotherapy in Patients with Glioblastoma: Is Less More?

MRI is the gold standard for treatment response assessments for glioblastoma. However, there is no consensus regarding the optimal interval for MRI follow-up during standard treatment. Moreover, a reliable assessment of treatment response is hindered by the occurrence of pseudoprogression. It is unknown if a radiological follow-up strategy at 2-3 month intervals actually benefits patients and how it influences clinical decision making about the continuation or discontinuation of treatment. This study assessed the consequences of scheduled follow-up scans post-chemoradiotherapy (post-CCRT), after three cycles of adjuvant chemotherapy [TMZ3/6], and after the completion of treatment [TMZ6/6]), and of unscheduled scans on treatment decisions during standard concomitant and adjuvant treatment in glioblastoma patients. Additionally, we evaluated how often follow-up scans resulted in diagnostic uncertainty (tumor progression versus pseudoprogression), and whether perfusion MRI improved clinical decision making. Scheduled follow-up scans during standard treatment in glioblastoma patients rarely resulted in an early termination of treatment (2.3% post-CCRT, 3.2% TMZ3/6, and 7.8% TMZ6/6), but introduced diagnostic uncertainty in 27.7% of cases. Unscheduled scans resulted in more major treatment consequences (30%; p < 0.001). Perfusion MRI caused less diagnostic uncertainty (p = 0.021) but did not influence treatment consequences (p = 0.871). This study does not support the current pragmatic follow-up strategy and suggests a more tailored follow-up approach.

THeragnostic utilities for neoplastic DisEases of the rectum by MRI guided radiotherapy (THUNDER 2) phase II trial: interim safety analysis

BackgroundThe THUNDER-2 phase II single institutional trial investigates the benefits of MRI-guided radiotherapy (MRIgRT) in treating locally advanced rectal cancer (LARC). This study focuses on evaluating the impact of escalating radiation therapy dose in non-responder patients using the Early Tumour Regression Index (ERI) for predicting complete response (CR). The trial’s primary endpoint is to increase the CR rate in non-responders by 10% and assess the feasibility of the delta radiomics-based MRIgRT predictive model. This interim analysis assesses the feasibility and safety of the proposed MRIgRT dose escalation strategy in terms of acute toxicity (gastrointestinal, genitourinary and haematological) and treatment adherence.MethodsStage cT2-3, N0-2, or cT4 patients with anal sphincter involvement, N0-2a, M0, but without high-risk features were enrolled. MRIgRT treatment consisted of a standard dose of 55 Gy to the Gross Tumor Volume (GTV) and mesorectum, and 45 Gy to the mesorectum and drainage nodes in 25 fractions with concomitant chemotherapy. 0.35 T MRI was used for simulation imaging and daily alignment. ERI was calculated at the 10th fraction. Non-responders with an ERI above 13.1 received intensified dose escalation from the 11th fraction, resulting in a total dose of 60.1 Gy. Acute toxicity was assessed using the CTCAE v.5 scale.ResultsFrom March 2021 to November 2022, 33 out of the total number of 63 patients to be enrolled (52.4%) were included, with one withdrawal unrelated to treatment. Sixteen patients (50%) underwent dose escalation. Treatment was well tolerated, with only one patient (3.1%) in the standard treatment group experiencing acute Grade 3 diarrhea, proctitis, and cystitis. No significant differences in toxicity were observed between the two groups (p = 0.5463).ConclusionsMRIgRT treatment with dose escalation up to 60.1 Gy is well tolerated in LARC patients predicted as non-responders by ERI, confirming the feasibility and safety of this approach. The THUNDER-2 trial’s primary and secondary endpoints will be fully analyzed when all planned patients will be enrolled.

FRI481 Clinical Characteristics Of Neutropenic Patients Under Anti-thyroid Drug: A Retrospective Cohort Study In Taiwan

Abstract Disclosure: C. Tseng: None. C. Tseng: None. H. Chen: None. P. Chen: None. C. Huang: None. Background: Thionamide-induced agranulocytosis (TiA), is a rare adverse event with a reported incidence of around 0.1-1.75%. To reduce mortality, prompt recognition is critical but the differential diagnosis of TiA cases from non-TiA neutropenia can be challenging as other causes of neutropenia, such as concomitant chemotherapy, liver dysfunction or infection, may simultaneously exist. The present study aimed at investigating the possible factors associated with the development of TiA. Method: This is a retrospective cohort study of patients treated with anti-thyroid drugs (ATDs) in Taipei Veterans General Hospital from 2006-2018. Patients who developed a neutropenic event under treatment of ATDs were identified from the medical records. TiA was defined as (1) development of neutropenia under treatment or within 7 days of previous exposure to the same ATDs; (2) total recovery of neutropenia within one month after discontinuation of the culprit drug with absolute neutrophil count &amp;gt; 1500/μL; (3) exclusion of other causes for neutropenia. The incidence and risk factors for developing TiA were analyzed and compared to those with non-TiA neutropenia. Results: Among 6644 patients treated with ATDs, 66 (mean age, 53±15 years; 16.2% men) developed a neutropenic event and 20 were diagnosed with TiA (incidence: 0.3%). In univariate analysis, TiA was associated with shorter treatment duration, lesser cumulative ATD dosage, higher ATDs dosage, higher absolute neutrophil count and higher free T4 level at the time of the neutropenic event, compared to non-TiA neutropenia. After accounting for age, gender and time to neutropenia, ATDs dosage at the time of neutropenic event [odds ratio (OR) and 95% confident intervals (CIs): 635.47, 1.88-214562.36], free T4 level (OR and 95% CIs: 17.23, 1.02-290.58), and absolute neutrophil count (OR and 95% CIs: 1.00, 1.00-1.01) were still independently associated with TiA in multivariable logistic regression. Conclusions: TiA patients were more likely to have higher free T4 level, higher absolute neutrophil count at the time of neutropenic event and had received higher dosage of ATDs, compared to non-TiA cases. Presentation: Friday, June 16, 2023

Predictive Value of Serum Biomarkers for Response of Limited-Stage AIDS-Associated Kaposi Sarcoma to Antiretroviral Therapy With or Without Concomitant Chemotherapy in Resource-Limited Settings.

Guidelines for limited-stage human immunodeficiency virus-associated Kaposi sarcoma (AIDS/KS) recommend antiretroviral therapy (ART) as initial treatment. However, many such individuals show worsening KS and require additional chemotherapy. Methods to identify such patients are lacking. We studied whether serum levels of biomarkers associated with angiogenesis, systemic inflammation, and immune activation, which are elevated in HIV-infected individuals and implicated in the development of KS, could prospectively identify individuals with limited-stage AIDS-KS who would benefit from chemotherapy administered with ART. Serum specimens were obtained from participants in a randomized trial evaluating the value of adding oral etoposide chemotherapy to ART in treatment-naïve people with limited-stage AIDS-KS in resource-limited settings. Serum biomarkers of inflammation (C-reactive protein [CRP], interleukin [IL]-6, IL-8, IL-10, granulocyte colony stimulating factor, soluble tumor necrosis factor receptor-2), immune system activation (soluble IL-2 receptor alfa, C-X-C motif chemokine ligand 10/interferon gamma-induced protein 10, C-C motif ligand 2/monocyte chemoattractant protein 1), and angiogenesis (vascular endothelial growth factor, matrix metalloproteinase-2, -9, endoglin, hepatocyte growth factor) were measured at entry to determine whether baseline levels are associated with KS response. On-treatment changes in biomarker levels were determined to assess how etoposide modifies the effects of ART. Pretreatment CRP and IL-10 were higher in those whose KS progressed, and lowest in those who had good clinical responses. Pretreatment CRP, IL-6, and soluble tumor necrosis factor receptor-2 showed significant associations with KS progression at the week-48 primary endpoint. Immediate etoposide led to lower inflammation biomarker levels compared with ART alone. Early KS progression was associated with elevated pretreatment levels of inflammation-associated biomarkers and increasing levels post-treatment. Quantifying serum biomarkers, especially CRP, may help identify persons with AIDS-KS who would benefit from early introduction of chemotherapy in addition to ART.

Comparative evaluation of oral mucositis in oral cancer patients undergoing 3-dimensional conformal radiation therapy and intensity modulated radiation therapy with or without chemotherapy.

Oral cancer is a significant cause of death across the world. A combined multimodal approach integrating surgery and radiation therapy (RT) with or without chemotherapy (CT) is commonly employed in advanced oral cancer to prevent recurrences and locoregional spread. Oral mucositis is a common acute toxicity reported in patients undergoing RT and CT. The delivery of optimal cancer therapy protocols is compromised due to morbidity caused by oral mucositis. To compare the severity of oral mucositis in oral cancer patients undergoing 3-Dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) with or without concomitant CT. This was a prospective, unicentric and longitudinal study conducted in a cancer centre. One hundred four patients with locally advanced oral cancer were enrolled in this study. Fifty-two patients were treated with IMRT and 52 patients with 3DCRT to a dose of >60 Gy, along with concurrent cisplatin weekly CT. Mucositis was recorded before the start, in the end, 1 month, and 3 months post-chemoradiotherapy treatment. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) software (v. 21.0, Chicago. 2012). Descriptive and frequency statistics were performed for different parameters assessed in 3DCRT and IMRT group. Grade 3 mucositis was the most predominant grade observed in both groups at the end of treatment. Thirty-six patients (69.3%) versus 24 patients (46.1%) developed grade 3 mucositis in 3DCRT and IMRT group, respectively (P = 0.013). Healing was better with IMRT group when compared to 3DCRT group 1 month and 3 months post-RT. Mucositis was severe in patients undergoing concomitant CT. IMRT reduced the incidence of severe mucositis and also improved the treatment-compliance compared to 3DCRT in locally advanced head neck cancer patients treated by chemoradiotherapy.

Unplanned Hospitalization and Subsequent Mortality in Lung Cancer Patients Undergoing Concomitant Chemo-/Immuno-Therapy and Radiotherapy: An Analysis of Over 10,000 Patients in a Nationwide Database

Radiotherapy (RT) and concomitant chemotherapy (CHT) is a major modality for treating many malignancies including lung cancer and is associated with toxicity-related unplanned hospitalization (UPH). Previous investigations of factors associated with UPH have been single institutional retrospective studies and none assessed the role of concurrent immunotherapy (IO). Here, we aimed to identify factors associated with UPH and in-hospital mortality by leveraging a multi-institutional nationwide database. The Vizient® Clinical Data Base which includes data from 98% of the AAMC hospitals and 110 cancer hospitals, was queried for lung cancer patients (any histology) treated in 2019-2021 with RT+CHT/IO. Endpoints were UPH and mortality during or within 30 days of completion of RT. The variables included age, sex, race, ethnicity, income level (quartile), an education level (quartile), any concomitant CHT or IO drugs, RT technique (3D vs. IMRT vs. SBRT), obesity, prior hospitalization within 3 months, prior oncologic surgery within 3 months, prior CHT and/or IO within 3 months, insurance types, hospital types (Rural vs. Urban, AAMC vs. non-AAMC, NCCN vs. non-NCCN, bed size tertile). Logistic regression was performed to identify variables associated with UPH and in-hospital mortality. Data from the Vizient Clinical Data Base used with permission of Vizient, Inc. All rights reserved. A total of 10,337 patients were included. The rate of UPH and mortality among UPH was 24.5% and 3.2%, respectively. Factors associated with UPH included other races (vs. White, OR 1.44; 95% CI 1.11-1.88; p<0.001), living in a low income zip code (OR 1.7; 95% CI 1.39-2.09; p = 0.0006), living in a zip code with lower education attainment (OR 0.71; 95% CI 0.58-0.86; p = 0.0007), CHT/IO types (cis-etoposide vs. carbo-Taxol, OR 1.33; 95% CI 1.13-1.57; p<0.0001), obesity (OR 1.71; 95% CI 1.53-1.92; p<0.0001), prior hospitalization (OR 2.0; 95% CI 1.80-2.22; p<0.0001), prior oncologic surgery (OR 0.34; 95% CI 0.22-0.52; p<0.0001), other primary payers (vs. commercial; OR 1.75; 95% CI 1.37-2.23; p<0.0001), rural hospital (OR 1.3; 95% CI 1.07-1.62, p<0.01), small bed size (OR 0.59; 95% CI 0.5-0.71; p<0.0001). Factors associated with in-hospital mortality included CHT/IO type (p<0.0001, but cis-etoposide vs. carbo-taxol no difference), prior hospitalization (OR 0.34; 95% CI 0.2-0.56; p<0.0001), AAMC (OR 2.12; 95% CI 1.23-3.67; p = 0.007), bed size (OR 0.58; 95% CI 0.38-0.88; p<0.01). In the largest study to date regarding UPH and in-hospital mortality related to lung RT, we identified factors contributing to these endpoints. Future prospective studies are warranted to develop strategies to prevent these complications in high-risk populations.

A Comparative Analysis of Effect of HIV Infection on Outcomes of Cervical Cancer Treated with Radiotherapy

There is paucity of data on management of human immunodeficiency virus (HIV) positive cervical cancer and its clinical outcomes in Indian women. The primary objective of this study was to compare disease free survival (DFS) and overall survival (OS) between HIV-positive and HIV-negative patients receiving radiotherapy (RT) for cervical cancer. The secondary endpoints were toxicity and various factors affecting DFS and OS. Patients diagnosed with cervical cancer on histopathology and treated with RT with or without concomitant chemotherapy (CT) at an institution between 2015 and 2020 were included in this retrospective analysis. On the basis of HIV serology test, 70 patients were included in each arm, Arm A had HIV-negative patients and Arm B had HIV-positive patients. In both the arms, external beam radiotherapy (EBRT) in adjuvant or radical setting was given with a total dose of 46-50 Gy to whole pelvis and iliac nodes; 2 Gy/fraction daily as 5 fractions/week by conventional four-field box technique or conformal 3-dimensional radiotherapy (3DCRT) or Intensity modulated radiotherapy (IMRT). Concurrent cisplatin was administered as weekly 40mg/m2 to patients with ECOG< = 2, creatinine clearance >40mL/min in radical and adjuvant patients as indicated. CD4 counts ≥200 cells/mm3 was a prerequisite for concurrent cisplatin in Arm B. Intracavitary or interstitial brachytherapy was delivered as indicated. Statistical analysis was done using statistical software. Kaplan-Meier method used for all survival analysis. Log rank test was used to calculate statistical significance for various prognostic factors followed by Cox regression test for multivariate analysis. Median age was 46.5 years (range: 30-76). In Arm A, 62 patients (88.57%) and 5 patients (7.14%) received radical and adjuvant RT. In Arm B 61 patients (87.14%) and 2 patients (2.85%) were given radical and adjuvant RT. 66 patients (94.28%) in Arm A and 52 patients (74.28%) in Arm B received concurrent cisplatin. At a median follow up of 33.8 months (range: 1.2 to 85.4), 2-year DFS was 88.9% for Arm-A and 86.5% for Arm-B (p = 0.134) and 2-year OS was 91.4% and 82.9% for Arm-A and Arm-B (p = 0.001), respectively. Grade III/IV skin toxicity was seen in and 4 patients (5.71%) in Arm A and 12 patients (17.14%) in Arm B (p = 0.34). Grade III/IV gastrointestinal toxicity was seen in 2(2.85%) patients and 4(5.7%) patients in Arm A and Arm B respectively (p = 0.40). 14(20%) patients in Arm A and 27(38.5%) patients in Arm B had Grade III/IV hematologic toxicity (p = 0.016). On multivariate analysis, anemia (Hb≤12 gm/dl) and OTT ≥56 days were associated with unfavorable DFS (p = 0.03 and p = 0.001) and OS (p = 0.04 and p = 0.01) in Arm B. In view of comparable DFS outcomes in both the arms, HIV-positive cervical cancer patients can be managed with the standard treatment protocol as HIV-negative patients. HIV-positive patients are more likely to experience poorer DFS and OS. However, results need to be validated on prospective study.

Treatment Outcomes of Concurrent Nimotuzumab with Intensity Modulated Radiotherapy in Advanced Nasopharyngeal Carcinoma Patients Unfit for Concurrent Chemoradiotherapy: A Single Institute Experience

To assess the safety and efficacy of intensity-modulated radiotherapy (IMRT) combined with nimotuzumab for patients with locally advanced nasopharyngeal carcinoma (LA-NPC) medically unfit to receive concomitant chemotherapy. From 2016.6 to 2020.9, 34 newly diagnosed patients with local-regional advanced NPC medically unfit for concurrent chemoradiation had undergone definitive radiotherapy and were retrospectively evaluated. All patients were treated with IMRT combined treatment modality of nimotuzumab with or without cisplatin-based induction chemotherapy. Nimotuzumab was administered concurrently with IMRT at a weekly dose of 200 mg. Acute and late radiation-related toxicities were evaluated based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 during and after IMRT. The Kaplan-Meier method was used for survival analysis. Univariate and multivariate prognostic analyses were performed by using the Cox proportional hazard model. The median follow-up time for the entire group was 15 months (range 5 to 55 months). At the time of this analysis, a total of 2 cases developed loco-regional recurrence. In addition, 4 patients developed distant metastasis. There was a total of 5 deaths: 3 patients died from distant metastasis, 1 patient died from the progression of loco-regional disease after recurrence, and the causes of death for the additional 1 case was a nasopharyngeal ulcer and deadly bleeding. The 1-year OS rate of the whole cohort was 87.9%, and the 1-year LFFR, DFFR, and PFS rates were 100%, 91.0%, and 91.0%, respectively. During the period of concurrent nimotuzumab and IMRT, no grade 3-4 hematologic toxicities and dermatitis were observed. Grade 3-4 radiotherapy-related oral mucositis was reported in 7 patients (20.6%). No infusion reaction was observed. No acneiform eruptions were found among these patients. The most commonly observed late complication was xerostomia. The degree of dry mouth in most patients was mild-to-moderate at the time of the last follow-up. Finally, 7 patients developed either unilateral or bilateral hearing impairment. One female patient experienced a nasopharyngeal ulcer and deadly bleeding after 5 months of completion of radiotherapy. Concurrent nimotuzumab with IMRT for the treatment of LA-NPC was well tolerated, with encouraging survival data, and it could be an effective treatment alternative for patients with LA-NPC medically unfit for concomitant chemotherapy. Further clinical trials are needed to confirm these findings.

TREATMENT OUTCOMES OF UTERINE CARCINOMA: A SINGLE INSTITUTION RETROSPECTIVE STUDY

BackgroundEndometrial cancer has a lifetime risk of 2.6% for women living in industrialized countries and it is the most prevalent kind of cancer diagnosed in those regions. In terms of gynecologic cancer-related deaths, it ranks after ovarian and cervical cancer as the third most common cause.&#x0D; ObjectivesTo evaluate endometrial cancer patients’ long-term treatment outcomes, including disease-free survival and overall survival, as well as to pinpoint independent predictive markers.&#x0D; Materials and MethodsAt the Zhianawa Cancer Center, a retrospective analysis was conducted. All patients who had been referred for radiation therapy between March 2009 and January 2019 were included in the research, except those who had distant metastases. In the end, 89 patients were included. Using the Kaplan-Meier technique, overall survival and disease-free survival were calculated, and the significance of the variations across curves was evaluated using the log-rank test.&#x0D; ResultsAll patients underwent surgery, 96.6% received adjuvant radiotherapy, and 42.7% received concomitant chemotherapy. The 5-year and 10-year disease-free survivals were 62.9% and 56.2%, and the overall 5-year and 10-year survivals were 74.2% and 66.3% respectively. The statistically significant variables impacting disease-free survival were lymphovascular invasion and marginal status, and the only statistically significant prognostic variable affecting overall survival was the FIGO stage.&#x0D; ConclusionIn this analysis, we concluded that uterine cancer has a good prognosis, and its outcome was influenced by stage, lymphovascular space invasion, and surgical marginal status.