Outcomes Of Chemoradiotherapy Research Articles

Specific association of MTHFD1 expressions with small cell lung cancer development and chemoradiotherapy outcome.

To identify biomarkers that can discriminated small cell lung cancer (SCLC) from non-SCLC (NSCLC), and explore their association with the prognosis of SCLC under chemoradiotherapy. The GSE40275 dataset was used to identify potential targets in SCLC. There were 196 patients of lung cancer (LC) in cohort 1 of this study. MTHFD1 levels in tissues were determined by immunohistochemistry assay in cohort 1. Lung cancer patients who were all underwent local chemoradiotherapy (CRT) were included in cohort 2, and the association of MTHFD1 levels with CRT treatment outcome were determined in cohort 2. Cell experiments were used to determine the function of MTHFD1 on the radio-sensitivity of SCLC and NSCLC cells. The MTHFD1 levels in LC tissues were increased, and could discriminate SCLC from both lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD). Small cell lung cancer patients with MTHFD1 high phenotype had a poorer prognosis after CRT treatment, whereas no significant correlation was found between MTHFD1 levels and prognosis in LUSC and LUAD group. Cell experiments demonstrated that overexpression of MTHFD1 increases radio-resistance in both SCLC and NSCLC in vitro. MTHFD1 expressions might be a novel specifically prognostic biomarker for SCLC and the CRT treatment outcome.

Survival outcome of esophagectomy and chemoradiotherapy for resectable esophageal squamous cell carcinoma in patients >75 years of age.

The gold standard for resectable, locally advanced esophageal squamous cell carcinoma (ESCC) is surgery-based treatment; however, it is unclear whether esophagectomy or chemoradiotherapy is suitable for older patients. This retrospective study aimed to identify the treatment outcomes of surgery-based therapy versus definitive chemoradiotherapy (dCRT) as an initial treatment for older patients with resectable, locally advanced ESCC. Data from 434 patients who received radical treatment for resectable, locally advanced ESCC were collected from January 2011 to December 2020. Of the patients >75 years of age, 49 underwent radical esophagectomy and 26 received dCRT. Survival was compared between the surgery and dCRT groups. The mean ages of the surgery and chemoradiotherapy groups were 77.3 and 78.8 years, respectively. Differences in overall survival (OS) between the two groups were not statistically significant (3-year OS: surgery 66.2%, dCRT 55.7%, p = 0.236). Multivariate analysis for OS showed a hazard ratio of 1.229 for dCRT versus surgery (90% confidence interval 0.681-2.217). OS did not differ between the groups in any of the performance statuses. For patients who were able to receive chemotherapy using fluorouracil and cisplatin, OS tended to be better in the surgery group, but the difference was not statistically significant (3-year OS: surgery 68.1%, dCRT 51.8%, p = 0.117). There was no clear difference in survival outcome between surgery-based therapy and dCRT as an initial treatment for esophageal cancer in older patients. Either treatment may be an option for older patients.

Three-year outcomes of preoperative chemoradiotherapy plus nivolumab in microsatellite stable and microsatellite instability-high locally advanced rectal cancer.

Preoperative chemoradiotherapy (CRT) followed by surgery is the standard treatment for locally advanced rectal cancer (LARC). We reported the short-term outcomes of the VOLTAGE trial that investigated the safety and efficacy of preoperative CRT followed by nivolumab and surgery. Here, we present the 3-year outcomes of this trial. Thirty-nine patients with microsatellite stable (MSS) LARC and five patients with microsatellite instability-high (MSI-H) LARC underwent CRT (50.4 Gy) followed by five doses of nivolumab (240 mg) and surgery. The 3-year relapse-free survival (RFS), overall survival (OS), and associations with biomarkers were evaluated. The 3-year RFS rates in patients with MSS and MSI-H were 79.5% and 100%, respectively, and the 3-year OS rates were 97.4% and 100%, respectively. Of the MSS patients, those with pre-CRT PD-L1 positivity, pre-CRT high CD8 + T cell/effector regulatory T cell (eTreg) ratio, pre-CRT high expression of Ki-67, CTLA-4, and PD-1 had a trend toward better 3-year RFS than those without. Three-year outcomes of patients with MSI-H were better than those of patients with MSS. PD-L1 positivity, elevated CD8/eTreg ratio, and high expression of Ki-67, CTLA-4, and PD-1 could be positive predictors of prognosis in patients with MSS. ClinicalTrials.gov Identifier: NCT02948348.

Comparison of Outcome of Concurrent Chemoradiotherapy and Sequential Chemoradiotherapy in Locally Advanced, Inoperable Squamous Cell Carcinoma of Head and Neck Region

Background: Head and neck cancer is prevalent in Bangladesh, with a majority of patients presenting with locally advanced, inoperable disease. This study aimed to compare the effectiveness and accessibility of concurrent and sequential (CCRT with RT) chemoradiotherapy in treating this condition, addressing a debate among oncologists. Materials and Methods: A quasi-experimental study at Rajshahi Medical College Hospital (June 2019 - May 2020) involved 60 inoperable head and neck cancer patients, comparing concurrent chemoradiotherapy with Cisplatin and sequential chemoradiotherapy with Paclitaxel and Cisplatin, monitoring treatment response and toxicities. Results: The mean age was 56.1 (±9.5) years in Arm-A and 56.9 (±9.4) years in Arm-B. The primary endpoint was loco-regional control and early toxicities. In the final response, 14 weeks after the completion of treatment, the overall loco-regional control rate was 86.67% and 76.67% in Arm-A and Arm-B, respectively. Severe toxicities include grade 3 reaction only and happened 18(58%) vs 13(42%) in Arm-A and Arm-B, respectively. Among severe toxicities, mucositis and skin reaction were higher in the concurrent Arm and anemia and neutropenia were higher in the sequential Arm. However, there was no actual difference in the two treatment modalities (p=>0.05). The overall treatment time was short in concurrent chemoradiotherapy (49 vs 133 days) and lower treatment cost as well, which was statistically significant (p=<0.0001). Conclusion: concurrent chemoradiotherapy proves cost-effective and accessible, demonstrating outcomes similar to sequential chemoradiotherapy. It stands as a viable treatment choice for locally advanced, inoperable head and neck squamous cell carcinoma.

Comparison of the Clinical Outcomes of Esophagectomy and Concurrent Chemoradiotherapy in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma.

The efficacy of concurrent chemoradiotherapy (CCRT) or esophagectomy for locally advanced esophageal squamous cell carcinoma (ESCC) is unclear. This study compared the survival and recurrence of patients with locally advanced ESCC after definitive CCRT and surgery. A retrospective study was conducted on patients with locally advanced ESCC who underwent CCRT or esophagectomy at Kosin University Gospel Hospital from January 2010 to December 2016. The patients' baseline characteristics, pathology, recurrence rate, and three-year/five-year overall survival were obtained. This study evaluated ESCC patients with cT1-T2, N+ or cT3-T4, or N, who were treated by definitive CCRT (n=14) or esophagectomy (n=32). No significant difference was noted between the two groups, except for the location of the cancer and performance state. The respective three- and five-year overall survival rates were 30.8% and 23.1% in the CCRT group and 40.2% and 22.5% in the esophagectomy group (p=0.685). In the CCRT group, three patients (21.4%) had a complete response, and two (66.7%) had a recurrence. In the esophagectomy group, an R0 resection was achieved in 28 (87.5%) patients, and a recurrence occurred in 18 (64.3%). The median disease-free survival in the CCRT and esophagectomy groups was 14 and 17 months, respectively (p=0.882). These results showed no significant difference in survival between the definitive CCRT and surgery as the initial treatment. Nevertheless, larger prospective studies will be needed because of the retrospective nature and small number of patients in this study.

Abstract 5143: Molecular investigation of a polymorphic variant in JMJD1C that associates with chemoradiotherapy outcomes in locally advanced rectal and head and neck cancer

Abstract Background: Neoadjuvant chemoradiotherapy (nCRT) is standard therapy for locally advanced rectal cancer (LARC). While only a minority of patients are expected to have a complete response, all are at risk of toxicity. Currently no biomarkers reliably predict response to nCRT in LARC. Further, standard therapy in locally advanced head and neck squamous cell carcinoma (HNSCC) is adjuvant CRT. A major cause of poor outcomes in HNSCC is regional persistence or recurrence post-CRT. No biomarkers, apart from HPV, predict CRT response in HNSCC. CRT causes double-strand breaks (DSBs) and methylation of histones on lysine residues is known to affect chromatin, influencing DSB repair. We hypothesized that single nucleotide polymorphisms (SNP) in the histone 3 lysine 9 (H3K9) demethylase-encoding JMJD1C influenced CRT response. Methods: LARC patients (n=84) were divided into poor (PoR) and complete (CR) responders based on Neoadjuvant Rectal score. Lymphocyte DNA was sequenced, and LARC patient-derived cells were treated with DSB-inducing agents to assess viability. Sequencing was confirmed in an independent cohort of CRT-treated HNSCC patients (n=90) divided into: disease-free (n=30), recurrent disease (n=28), and never-disease-free (n=32). HNSCCs were in the larynx or oral cavity. Not all patients received HPV-testing; p16 expression was positive for 19/43 tumors. CRISPR/Cas9 editing of HPV-negative HNSCC lines (SCC9, Cal27) generated JMJD1C WT or SNP isogenic pairs. Bulk RNA-sequencing, colony survival, and immunofluorescence studies were performed. Results: In LARC patients, CRs were enriched for a coding, missense germline SNP in JMJD1C versus PoRs (discovery n=30, p<0.00001; validation n=54, p=0.001, Fisher’s Exact). When subjected to DSB, LARC patient-derived cells with the SNP displayed greater sensitivity than their WT counterparts (n=12, p<0.001, Mann-Whitney). In HNSCC, a correlation was identified between the same JMJD1C SNP and no recurrence (p=0.0003, Fisher’s Exact). HNSCC SNP cells showed changes in mRNA levels of DNA repair and immune response genes versus HNSCC WT cells (q-value<0.05). Upon irradiation, kinetics of foci resolution of the DNA damage response protein MDC1, specific to DSBs, were slower in SNP versus WT HNSCC cells (p<0.05, Mann Whitney). Further, there was reduced colocalization of BRCA1 with RAP80, a crucial factor for homology-directed DSB repair, in SNP versus WT HNSCC cells (p<0.01, Mann-Whitney).Targeted introduction of the SNP into HNSCC cell lines reduced viability and radiation response. Conclusion: Our study identifies a polymorphic coding variant in JMJD1C, as a predictive biomarker for CRT effectiveness in LARC and HNSCC, and defines a DNA repair mechanism by which JMJD1C influences response to irradiation. Citation Format: Adria Hasan, Elena V. Demidova, Philip Czyzewicz, Shreya M. Shah, Karthik Devarajan, Thomas J. Galloway, Margret B. Einarson, Barbara Burtness, Erica A. Golemis, Joshua E. Meyer, Sanjeevani Arora. Molecular investigation of a polymorphic variant in JMJD1C that associates with chemoradiotherapy outcomes in locally advanced rectal and head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5143.

Abstract 1192: Diversity of TCR repertoire on peripheral CD8+PD-1+ T-cell predicting the PFS of chemoradiotherapy followed by durvalumab maintenance in unresectable locally advanced NSCLC patients

Abstract Background: Chemoradiotherapy (CRT) followed by Durvalumab consolidation has been the standard treatment for unresectable locally advanced non-small cell lung cancer (LA-NSCLC) patients. This study aimed to evaluate how CRT changes TCR repertoire on peripheral CD8+PD-1+ T-cells, and the change affects the clinical outcomes of CRT followed by durvalumab treatment. Methods: This was a prospective cohort study conducted from November 2019 to May 2021 in three institutes (National Cancer Center Hospital, Kansai Medical University Hospital, and Aichi Cancer Center Hospital) in Japan. We revealed the diversity of TCR repertoire (diversity evenness 50 [DE50]) on PD-1+CD8+ T cells, and CD8+ T cell phenotype in PBMCs before and after CRT treatment. Results: A total of 40 patients treated with CRT were included. Of these patients, 32 patients received durvalumab consolidation treatment after CRT (Durva cohort). The diversity and usage of T cell Receptor Beta Variable (TRBV) and T-cell receptor beta joining gene (TRBJ) usage were significantly positively correlated before and after CRT (TRBV usage: r=0.62, p<0.001, TRBJ usage: r=0.55, p<0.001). Regarding the association of TCR repertoire diversity with CD8+ T cell phenotype, DE50 and frequencies of CD8 naive were significantly positively correlated before CRT (p=0.049), while there was no correlation between PD-L1 expression and TCR repertoire before CRT (r=0.03, p=0.89) In Durva cohort, DE50 in patients with non-recurrence was higher than those with recurrence both before and after CRT (Before CRT: 0.0032 vs. 0.0019, p=0.13, After CRT: 0.0026 vs. 0.0014, p=0.06). The progression-free survival (PFS) of patients with DE50High before CRT was significantly greater than those with DE50Low (NR vs. 14.3 months; p=0.01). Moreover, when the patients were exploratory classified based on the PD-L1 expression status and the diversity of TCR repertoire, the PFS of the CRT followed by durvalumab apparently differed (DE50High, PD-L1 TPS≥1%, NR, and DE50Low, PD-L1 TPS<1%, 5.9 (4.6-7.3) months, p=0.001). Conclusions: TCR diversity of peripheral CD8+PD-1+ T-cell predicted the recurrence in unresectable locally advanced NSCLC patients treated with chemoradiotherapy followed by durvalumab maintenance. Additionally, the TCR diversity combined with PD-L1 expression status could more accurately predict the efficacy of the CRT followed by durvalumab. Citation Format: Masayuki Shirasawa, Tatsuya Yoshida, Yuki Takeyasu, Takaji Matsutani, Shigehiro Yagishita, Shigehisa Kitano, Hiroaki Kuroda, Toyoaki Hida, Takayasu Kurata, Yuichiro Ohe. Diversity of TCR repertoire on peripheral CD8+PD-1+ T-cell predicting the PFS of chemoradiotherapy followed by durvalumab maintenance in unresectable locally advanced NSCLC patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1192.

Neoplasia-related and treatment-induced lymphopenia: impact on the outcome of chemoradiotherapy in laryngeal cancer

Introduction The role of the immune system in the efficacy of radiotherapy (RT) has been well established. We examined the role of neoplasia-related and treatment-induced lymphopenia in the outcome of RT or chemoradiotherapy (CRT) in squamous cell laryngeal cancer. Materials and Methods We retrospectively analyzed a series of 135 laryngeal carcinomas treated with radical or postoperative RT/CRT. Six lymphocyte-related variables were defined and examined: i. lymphocyte counts (LCs) before a brief course of induction chemotherapy, ii. pre-RT LCs, iii. post-RT LCs, iv. pre-RT neutrophil/lymphocyte ratio (N/L), v. pre-RT monocyte/lymphocyte ratio (M/L), and vi. pre-RT platelet/lymphocyte ratio (Pt/L). Results RT and CRT resulted in a significant decrease of LCs at the end of therapy, and this was significantly more prominent in patients treated with radical intent and neck irradiation (median LC nadir 810/μl vs. 1250/μl; p = .0003). Induction chemotherapy did not intensify the lymphotoxic effect of RT. LCs lower than the 33rd percentile before RT (<1718/μl) and after RT (<720/μl) were significantly linked to poor locoregional progression-free survival (LRFS; p = .02 and p = .08, respectively) and disease-specific overall survival (OS; p = .02 and p = .03, respectively). This was also confirmed multivariate analysis (LRFS: p = .006/HR = 2.41 and p = .08/HR = 1.76, respectively; OS: p = .001/HR = 3.06 and p = .02/HR = 2.07, respectively). High pre-RT N/L, M/L, and Pt/L ratios were also of ominous prognostic relevance. Conclusions Both neoplasia-related and RT-induced lymphopenia define the outcome of RT in terms of locoregional failure, incidence of metastasis, and, finally, disease-specific survival of patients with laryngeal cancer. Restoration of pre-RT lymphopenia and protection of peripheral lymphocytes during RT emerge as critical issues that demand therapeutic interventions to maximize the efficacy of RT/CRT in patients with laryngeal cancer.

Mitochondria-related chemoradiotherapy resistance genes-based machine learning model associated with immune cell infiltration on the prognosis of esophageal cancer and its value in pan-cancer

Esophageal cancer, known for its high incidence and low five-year survival rate, poses significant treatment challenges. A key aspect of this challenge is the close link between mitochondria and resistance to chemoradiotherapy (CRT). Currently, there is a scarcity of biomarkers for predicting CRT response and prognosis in esophageal cancer. Our study addresses this gap by developing a prognostic model that incorporates mitochondria-related CRT resistance (MRCRTR) genes, including CTSL, TBL1X, CLN8, MMP1, PDPN, and MRPL37. Survival analysis using Kaplan–Meier curves reveals that patients with high MRCRTR scores have lower survival rates than those with low scores. Utilizing a nomogram, we successfully predict the one-, two-, and three-year overall survival rates for esophageal cancer patients. Cox regression analysis confirms the MRCRTR score as an independent prognostic factor. Furthermore, our single-cell and correlation analyses suggested that MRCRTR genes might influence CRT resistance by modulating the immune microenvironment and impacting angiogenesis. Our pan-cancer analysis also indicates the potential applicability of MRCRTR scores to head and neck squamous cell carcinoma. The validation of these findings, conducted with samples from Xiang-ya Hospital, aligns closely with our bioinformatics results. Our study not only explores the role of MRCRTR genes in predicting the prognosis of esophageal cancer but also enhances the understanding of the interplay between CRT, mitochondria, and patient outcomes.

Impact of nutritional intervention on concurrent chemoradiotherapy outcomes in locally advanced esophageal cancer: A pharmacological perspective

Purpose: To determine the pharmacological implications of nutritional intervention and the occurrence of toxic side effects in patients with locally advanced esophageal cancer undergoing concurrent chemoradiotherapy.&#x0D; Methods: An extensive retrospective analysis of clinical data was carried out on individuals who received concurrent chemo-radiotherapy. 150 patients were included in the study, with 85 patients receiving nutritional management (intervention group) and 65 patients without nutritional support (control group). Assessments were conducted for Nutritional Risk Screening-2002 (NRS-2002) and patient-generated subjective global assessment (PG- SGA) scores, serum nutritional parameters, toxic side effects and treatment completion rates at 2, 4, and 6 weeks before and during chemo-radiotherapy.&#x0D; Results: After concurrent chemo-radiotherapy, intervention group exhibited significantly lower NRS2002 and PG- SGA scores compared to control group (p = 0.002 and 0.001, respectively). Intervention group had a statistically significant increase in PALB (p = 0.001) and ALB, while control group experienced a significant decline in ALB (albumin) and PALB (pre-albumin) levels. Grip strength also significantly decreased in control group compared to intervention group (p = 0.003). Intervention group showed a significantly lower incidence of radiation esophagitis. Moreover, a smaller proportion of patients in intervention group experienced interruptions or delays in radiotherapy compared to control group (95 % vs. 83.3 %).&#x0D; Conclusion: Nutritional intervention has a pharmacological impact on maintaining nutritional status, reducing treatment toxicities and improving the completion rates of chemo- radiotherapy in patients with locally advanced esophageal cancer. Further investigations and longer-term studies are warranted to shed more light on the potential impact of nutritional interventions on the overall survival rates of these patients

Surgical outcomes of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy in patients of locally advanced carcinoma of esophagus: A prospective cross-sectional comparative study

Background: Neoadjuvant chemoradiotherapy + radiotherapy (NACT+RT) or neoadjuvant chemotherapy (NACT) has been shown to improve survival in locally advanced esophageal carcinoma (EC). Comparative evaluation of NACT+RT versus NACT is ambiguous. Aims and Objectives: The current study was designed to evaluate the outcomes of NACT+RT versus NACT in locally advanced EC. Materials and Methods: In this prospective cross-sectional study, patients with operable, non-metastatic squamous cell carcinoma, and adenocarcinoma of the mid and lower esophagus (T3–T4a) were treated with NACT (paclitaxel 175 mg/m2 plus carboplatin 5 Area under curve (AUC) every 3 weeks) or NACT+RT (NACT with 45 Gy in 25 fractions over 5 weeks). Response, R0 resections, post-operative complications, and recurrence were comparatively evaluated. Results: Of 40 enrolled patients, 20 received NACT and 20 received NACT+RT. In the NACT arm, 50% of patients had a partial response and 20% had disease progression. In the NACT+RT arm, 10% of patients had disease progression whereas 25% of patients had complete pathological response. Transhiatal esophagectomy was performed in 60% of patients in the NACT arm, whereas in the NACT+RT arm, 80% of patients had three-stage esophagectomy. The average surgery duration was numerically greater for the NACT+RT arm; blood loss was also greater. Pulmonary complications and anastomotic leak rate were higher in NACT+RT arm whereas other complications such as hoarseness of voice, and wound dehiscence were higher in the NACT arm. Conclusion: NACT+RT had better partial and complete response rates and low recurrence rates versus NACT. Post-operative complications were higher in the NACT+RT, especially pulmonary complications and anastomotic leak. Further, large-scale studies are warranted to confirm the efficacy of NACT versus NACT+RT in EC.

Analysis of definitive chemo-radiation outcomes in anal cancer: insights from a tertiary cancer center in the MENA Region.

Outcomes of chemo-radiation (CRT) for anal cancer in Middle East and North Africa (MENA) are scarce. We aim to report treatment outcomes for anal cancer treated at tertiary cancer center, with a particular focus on patients managed with non-oncological surgery prior definitive CRT. We conducted a retrospective review of patients diagnosed with locally advanced anal carcinoma, who underwent definitive CRT King Hussein Cancer Center, from January 2007 till January 2020. Patient demographics and disease characteristics were extracted, and a univariate chi-squared test was employed to assess the impact of chemotherapy type, HPV status, and pre-treatment non-oncological surgery on outcomes, including complete remission (CR), disease-free survival (DFS), and overall survival (OS). Kaplan-Meier tests were employed to analyze the obtained survival data. Among the 34 initially identified patients, 30 were eligible, 24 (80%) achieved CR. Notably, 20 out of 21 HPV positive patients achieved CR, versus 1 out 4 HPV-negative achieved CR, p=0.006The 5-years OS for HPV-positive patients was 89% compared with 25% for HPV-negative, p=0001. There was no statistical significant difference in patients outcomes as regard type of chemotherapy, radiation technique and non-oncologic resection prior to CRT. Herein, we reported the first series of anal cancer from our region. CRT had yielded an oncologic outcome comparable with series in the literature. HPV-positive patients demonstrated better results. Moreover, we found non-oncologic resection prior to CRT did not seem to impact the outcomes. Further studies are warranted to overcome the limitations of our study.

Common Variants in Osteopontin and CD44 Genes as Predictors of Treatment Outcome in Radiotherapy and Chemoradiotherapy for Non-Small Cell Lung Cancer.

Osteopontin (OPN)-CD44 signaling plays an important role in promoting tumor progression and metastasis. In cancer, OPN and CD44 overexpression is a marker of aggressive disease and poor prognosis, and correlates with therapy resistance. In this study, we aimed to evaluate the association of single nucleotide polymorphisms (SNPs) in the OPN and CD44 genes with clinical outcomes in 307 non-small cell lung cancer (NSCLC) patients treated with radiotherapy or chemoradiotherapy. The potential impact of the variants on plasma OPN levels was also investigated. Multivariate analysis showed that OPN rs11730582 CC carriers had a significantly increased risk of death (p = 0.029), while the CD44 rs187116 A allele correlated with a reduced risk of locoregional recurrence (p = 0.016) in the curative treatment subset. The rs11730582/rs187116 combination was associated with an elevated risk of metastasis in these patients (p = 0.016). Furthermore, the OPN rs1126772 G variant alone (p = 0.018) and in combination with rs11730582 CC (p = 7 × 10-5) was associated with poor overall survival (OS) in the squamous cell carcinoma subgroup. The rs11730582 CC, rs187116 GG, and rs1126772 G, as well as their respective combinations, were independent risk factors for unfavorable treatment outcomes. The impact of rs11730582-rs1126772 haplotypes on OS was also observed. These data suggest that OPN and CD44 germline variants may predict treatment effects in NSCLC.

Induction chemoimmunotherapy may improve outcomes of chemoradiotherapy in patients with unresectable stage III NSCLC.

Currently, the value of induction chemoimmunotherapy before chemoradiotherapy (CRT) in unresectable stage III non-small cell lung cancer (NSCLC) has not been explored. This study was designed to explore the efficacy and safety of induction chemoimmunotherapy in patients with unresectable stage III NSCLC. Unresectable stage III NSCLC patients who received CRT with or without induction chemoimmunotherapy between August 2014 and December 2021 were retrospectively enrolled. Progression-free survival (PFS) and overall survival (OS) were assessed from the initiation of treatment and estimated by the Kaplan-Meier method. The potential factors affecting PFS and OS were analyzed by univariate and multivariate Cox regression models. One-to-one propensity score matching (PSM) was used to further minimize confounding. A total of 279 consecutive patients were enrolled, with 53 (19.0%) receiving induction chemoimmunotherapy followed by CRT (I-CRT group), and the remaining 226 (81.0%) receiving CRT alone (CRT group). After PSM, the median PFS was 24.8 months in the I-CRT group vs. 13.3 months in the CRT group (P=0.035). The median OS was not reached (NR) vs. 36.6 months ((P=0.142). The incidence of treatment-related adverse events (TRAEs) was similar in both groups, except that the incidence of hematological toxicity was higher in the I-CRT group (77.1% vs. 58.3%, P=0.049). Compared to induction chemotherapy, induction chemoimmunotherapy demonstrated a superior objective response rate (60.4% vs. 22.2%, P<0.001) and further prolonged PFS (median NR vs. 13.2 months, P=0.009) and OS (median NR vs. 25.9 months, P=0.106) without increasing the incidence of TRAEs in patients receiving concurrent chemoradiotherapy. Induction chemoimmunotherapy is safe and may improve outcomes of CRT in patients with unresectable stage III NSCLC. Moreover, induction chemoimmunotherapy may further improve treatment response and survival outcomes compared to induction chemotherapy before cCRT.

EP08.02-02 Real World Chemoradiotherapy Outcomes for Frail Older Adults with Unresectable Stage III Non Small Cell Lung Cancer (NSCLC)

EP08.02-02 Real World Chemoradiotherapy Outcomes for Frail Older Adults with Unresectable Stage III Non Small Cell Lung Cancer (NSCLC)

Clinical Outcomes and Immunotoxicity in People with HIV (PWH) after Definitive Chemoradiation (CRT) for Anal Squamous Cell Carcinoma

Anal cancer disproportionately affects PWH despite antiretroviral therapy. Data on CRT outcomes are limited. Modern IMRT CRT decreases acute toxicity but may exacerbate immune dysregulation from chronic HIV. Although historical CRT has been associated with prolonged CD4 count suppression, little is known about late immunotoxicity in PWH after contemporary CRT. We report clinical outcomes and long term immunotoxicity. Single-center retrospective review of all PWH confirmed on chart review with anal squamous cell carcinoma without prior pelvic irradiation treated with definitive IMRT CRT. Patient and CRT factors including HIV suppression (<200 copies/mL), mean CD4 count (cells/µL), and receipt of capecitabine (C) or 5-fluorouracil (F) +/- mitomycin (M) were summarized with n (%) or median (interquartile range). Progression-free and overall survival (PFS; OS) were estimated per Kaplan-Meier with 95% confidence intervals and compared with log-rank tests. Mean CD4 count and CD4:CD8 were compared by HIV suppression status (Welch's t-test); longitudinal changes in median CD4 count and CD4:CD8 were compared between baseline vs. nadir (within 6 months of CRT start) and 1-year follow-up for patients with complete data (Wilcoxon signed-rank test). A total of 23 PWH were treated between 2010-2022, median age 52, median 16 (13 - 19) years after HIV diagnosis; 4 had unsuppressed HIV; AJCC 8th stage I/II/III/IV 5/5/12/1. Radiation dose was median 54 Gy in 30 fractions over 42 (40 - 44) days. Most had C+M (57%); only 43% had 2×M with either C or F. One had neoadjuvant carboplatin/paclitaxel/pembrolizumab. With 2.9 (1.03 - 3.3) years follow-up, median OS was 6.6 (6.2 - unreached [UR]) years. With 2.2 (0.67 - 2.7) years follow-up, median PFS was UR. OS and PFS were similar regardless of HIV suppression status (both P ≥ 0.09). Overall baseline CD4 count was 458 (226 - 484), and CD4:CD8 was 0.54 (0.2 - 0.7). Nadir CD4 was 100 (59 - 126) and CD4:CD8 was 0.3 (0.2 - 0.4). Baseline and nadir CD4 count and CD4:CD8 were lower if HIV-unsuppressed (each P ≤ 0.04). One year after CRT, CD4 count was 252 (102 - 276), while CD4:CD8 was 0.5 (0.2 - 0.7). For 7 patients with repeated values the change in median from baseline to nadir, 6-, and 12-months post-CRT was -282, -549 (both P = 0.02), -480 (P = 0.9) for CD4 counts, and -0.7, -0.5, -0.4 (each P > 0.5) for CD4:CD8 ratios; none had unsuppressed HIV. Definitive IMRT CRT with guideline-concordant doublet chemotherapy for anal cancer in PWH is effective despite unsuppressed HIV. Treatment leads to prolonged immunological changes that may increase the risk of HIV-related morbidity and mortality. Modifiable treatment-related causes of hematoimmunologic toxicity should be investigated further, and immune surveillance after CRT should be considered to better understand impact on quality of life.

Radical Chemoradiotherapy vs. Radical Surgery plus Adjuvant Chemotherapy or Chemoradiotherapy in Locally Advanced Primary Small Cell Carcinoma of the Esophagus: A Multicenter Retrospective Study in China

The purpose was to compare the treatment outcomes of radical chemoradiotherapy versus radical surgery plus adjuvant chemotherapy or chemoradiotherapy in locally advanced primary small cell carcinoma of the esophagus (LA-PSCCE). The hypothesis was that radical chemoradiotherapy had better overall survival (OS) than radical surgery plus adjuvant chemotherapy or chemoradiotherapy. This large-scale multicenter retrospective study in China enrolled patients with newly diagnosed LA-PSCCE (T3-4N0M0 or TanyN+M0, AJCC 8th edition) from 2008 to 2021. According to different curative treatment approaches, patients were divided into two groups: radical chemoradiotherapy (group: CRT), and radical surgery following adjuvant chemotherapy or chemoradiotherapy (group: S + CT/CRT). The propensity score match (PSM) was applied to reduce the effect of confounding biases in clinicopathological characteristics (age, gender, KPS, tumor location, tumor length, and cTNM stage). Univariate Cox-regression analysis and Kaplan-Meier curve were calculated for OS. Statistical results were summarized as hazard ratio (HR), 95% confidence interval (CI) and P value. A two-sided P < 0.05 was regarded to be statistically significant. A total of 291 patients with a median follow-up of 4.3 years were retrospectively enrolled. After PSM analysis, 94 and 94 patients were eventually included in group CRT and S + CT/CRT, respectively. Group CRT demonstrated a significantly superior survival than group S + CT/CRT (HR, 0.63; 95% CI, 0.43-0.91; P = 0.01), with a 3-year OS of 49.5% and 27.8% (P = 0.02), respectively. In secondary analysis, patients treated with radical chemoradiotherapy consistently showed significant survival benefit than those with radical surgery plus adjuvant chemoradiotherapy (HR, 0.4; 95% CI, 0.21-0.79; P = 0.008). For patients with newly diagnosed LA-PSCCE, radical chemoradiotherapy should be a preferred recommendation in real-world clinical practice.

Amide proton transfer (APT) and magnetization transfer (MT) in predicting short-term therapeutic outcome in nasopharyngeal carcinoma after chemoradiotherapy: a feasibility study of three-dimensional chemical exchange saturation transfer (CEST) MRI

BackgroundThe three-dimensional chemical exchange saturation transfer (3D CEST) technique is a novel and promising magnetic resonance sequence; however, its application in nasopharyngeal carcinoma (NPC) lacks sufficient evaluation. This study aimed to assess the feasibility of the 3D CEST technique in predicting the short-term treatment outcomes for chemoradiotherapy (CRT) in NPC patients.MethodsForty NPC patients and fourteen healthy volunteers were enrolled and underwent the pre-treatment 3D CEST magnetic resonance imaging and diffusion-weighted imaging (DWI). The reliability of 3D CEST was assessed in healthy volunteers by calculating the intra- and inter-observer correlation coefficient (ICC) for amide proton transfer weighted-signal intensity (APTw-SI) and magnetization transfer ratio (MTR) values. NPC patients were divided into residual and non-residual groups based on short-term treatment outcomes after CRT. Whole-tumor regions of interest (ROIs) were manually drawn to measure APTw-SI, MTR and apparent diffusion coefficient (ADC) values. Multivariate analysis and the receiver operating characteristic curve (ROC) were used to evaluate the prediction performance of clinical characteristics, APTw-SI, MTR, ADC values, and combined models in predicting short-term treatment outcomes in NPC patients.ResultsFor the healthy volunteer group, all APTw-SI and MTR values exhibited good to excellent intra- and inter-observer agreements (0.736–0.910, 0.895–0.981, all P > 0.05). For NPC patients, MTR values showed a significant difference between the non-residual and residual groups (31.24 ± 5.21% vs. 34.74 ± 1.54%, P = 0.003) while no significant differences were observed for APTw-SI and ADC values (P > 0.05). Moreover, the diagnostic power of MTR value was superior to APTw-SI (AUC: 0.818 vs. 0.521, P = 0.017) and comparable to ADC values (AUC: 0.818 vs. 0.649, P > 0.05) in predicting short-term treatment outcomes for NPC patients. The prediction performance did not improve even when combining MTR values with APTw-SI and/or ADC values (P > 0.05).ConclusionsThe pre-treatment MTR value acquired through 3D CEST demonstrated superior predictive performance for short-term treatment outcomes compared to APTw-SI and ADC values in NPC patients after CRT.

Genetic and epigenetic alterations in MGMT gene and correlation with concomitant chemoradiotherapy (CRT) in cervical cancer.

The MGMT (O6-methylguanine-DNA methyltransferase) gene plays a crucial role in repairing DNA damage caused by alkylating agents, including those used in chemotherapy. Genetic and epigenetic alterations can influence the regulation of MGMT gene, which in turn may impact the response to concomitant chemoradiotherapy (CRT) in cervical cancer. The present study was undertaken to evaluate the correlation of such variations in MGMT gene with the treatment outcome of concomitant chemoradiotherapy (CRT) in cervical cancer. A total of 460 study subjects (240 controls and 220 patients) were subjected to genotypic analysis of MGMT gene variants rs12917(T/C) and rs2308327(A/G) by Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). Out of them, 48 each of controls and patients were analyzed for promoter methylation and expression by methylation-specific PCR and real-time PCR, respectively. Patients (n = 48) were followed up and evaluated for treatment (CRT) outcome. Statistical analyses were done using GraphPad (9.0) and SPSS version 18.0. Individuals with GG genotype, G allele of rs2308327, and haplotype 'TA' of both variants showed a significant increase in the development of cervical cancer (P ≤ 0.05). In epigenetic regulation, there was a significant hypermethylation of MGMT gene and down-regulation of their expression in patients compared to control individuals. In treatment outcome of CRT, GG genotype of rs2308327(A/G) gene variant showed better response and GG + AG was significantly associated with vital status (alive). Unmethylated MGMT gene showed better median overall survival up to 25months significant in comparison to methylated MGMT promoter. Gene variant rs2308327(A/G) and promoter hypermethylation regulated MGMT gene can be a good prognostic for treatment response in cervical cancer patients.

Peri-operative chemotherapy versus preoperative chemoradiotherapy in treatment of gastro-oesophageal junctional adenocarcinomas: A 10-year cohort study

BackgroundGastro-oesophageal junctional (GOJ) cancers have been, more latterly, considered a distinct tumor entity with characteristic genetic profiles. The optimal multimodal therapy of advanced GOJ cancers remains debatable. In this comparative study, we analyzed the outcomes of peri-operative chemotherapy (CT) versus pre-operative chemoradiotherapy (CRT) in treatment of advanced GOJ adenocarcinomas. MethodsThis study included patients with locally advanced but resectable GOJ adenocarcinomas who underwent surgical resection after oncological therapy between 2010 till 2019 at our institution. Follow up to May 2021 was completed. The outcomes between CT and CRT groups were retrospectively analyzed. The long-term follow up data was obtained via direct contact with the patients during oncological clinics, cross-checked with hospital/national patients’ electronic databases. Results107 patients had GOJ cancers; 90 (84%) patients met our inclusion criteria. Perioperative chemotherapy was administrated in 65 (72%) patients. Overall median survival rate was 2.2 years in CRT-group compared to 2.4 years in CT-group (p-value 0.29), with comparable recurrence rates (48% vs 36% respectively). R0-resections were higher in CRT-group (84%) compared to CT-group (71%), yet insignificant p-value 0.197. Preoperative chemoradiotherapy achieved higher complete pathological response (28% vs 6%, p-value 0.009) and negative lymph nodes rates (64% vs 37%, p-value 0.014) compared to CT-group. Short-term outcomes (postoperative complications, morbidity rates and length of hospital stay) were similar across both groups. ConclusionPreoperative chemoradiotherapy was associated with higher complete pathological response and negative lymph nodes rates for GOJ adenocarcinomas compared to peri-operative chemotherapy, without an increase in postoperative complications or morbidity rates. However, it wasn't associated with improved overall or disease-free survival rates.