Chemoradiotherapy In Patients Research Articles

Primary chemoradiation versus neoadjuvant chemotherapy followed by surgery as treatment strategy for locally advanced vulvar carcinoma (VULCANize2)

BackgroundCurrent treatment options for patients with locally advanced vulvar cancer are limited and associated with high morbidity. Therefore, it is important to develop new and safe treatment strategies for this...

Statement of the Uterus Commission of the Gynecological Oncology Working Group (AGO) on Neoadjuvant Chemotherapy Prior to Definitive Radiochemotherapy in Patients with Locally Advanced Cervical Cancer

AbstractThe presentation of the results of the prospective randomized international multicenter GCIG INTERLACE trial at the 2023 congress of the European Society of Medical Oncology (ESMO) is likely to change the therapy for locally advanced cervical cancer. In the GCIG INTERLACE trial, six cycles of neoadjuvant chemotherapy administered weekly and consisting of carboplatin AUC2 and paclitaxel 80 mg/m2 followed by definitive radiochemotherapy with pelvic radiotherapy (40 – 50.4 Gray) and cisplatin (40 mg/m2 once a week for 5 weeks) and brachytherapy (total dose EQD2 at least 78 Gy at point A) (experimental arm) were compared with definitive radiochemotherapy alone (standard arm) in patients with locally advanced cervical cancer (Fédération Internationale de Gynécologie et dʼObstétrique [FIGO] 2008 stage IB1/node positive, IB2, II, IIIB and IVA) and was found to be significantly superior with significantly longer recurrence-free survival (hazard ratio [HR] 0.65; 95% confidence interval [CI] 0.64 – 0.91; p = 0.013) and significantly longer overall survival rates (HR 0.61; 95% CI: 0.40 – 0.91; p = 0.04) after 5 yearsʼ follow-up. After considering the results of the GCIG INTERLACE trial published at the congress, the Uterus Commission of the AGO is of the opinion that neoadjuvant chemotherapy with carboplatin AUC2 and paclitaxel 80 mg/m2 d1, q7, x6 may be offered to patients with locally advanced cervical cancer (FIGO stage IB1/node positive, IB2, II, IIIB and IVA) in addition to the current standard therapy after the patient has been informed about the risks, with the decision taken on a case-by-case basis. However, before this approach can be discussed at guideline level or defined as the new therapy standard, it will be necessary to wait until the data from the full publication are available.

Abstract CT080: A phase I study of CPI-613 (devimistat) in combination with chemoradiation in patients with pancreatic ductal adenocarcinoma

Abstract Background: Local tumor progression is a cause of significant mortality and morbidity in patients (pts) with inoperable pancreatic ductal adenocarcinoma (PDAC). Effective approaches to achieve durable local control are urgently needed. Metabolic reprogramming and enhanced mitochondrial function are known contributors to chemo- and radio-resistance in PDAC. CPI-613, a lipoic acid analog that selectively inhibits components of the Krebs cycle in tumors, showed promising preclinical synergy in combination with gemcitabine and radiation (gem-RT). We initiated a phase I study (NCT05325281) to determine the maximum tolerated dose (MTD) of CPI-613 when used with gem-RT. Here, we present the results from the first cohort of this study. Methods: Adult pts with inoperable PDAC that, by institutional multidisciplinary review, were considered to benefit from definitive local control of the primary tumor were eligible for the study. CPI-613 was administered once weekly by intravenous infusion over ~ 2 hours at a starting dose of 500 mg/m2 and dose-escalated using a Bayesian optimal interval design. Gemcitabine was given once weekly at 400 mg/m2 and RT at 45-54 Gray (Gy) in 25-30 fractions. Results: By Jan 7, 2024, six pts were enrolled, and five completed the treatment and dose-limiting toxicity (DLT) period. Table 1 describes the characteristics of these five pts. As CPI-613 was not associated with any additional toxicities, specifically cytopenia(s), after the first two pts, the study protocol was amended to allow CPI-613 to be administered on weeks gemcitabine was held for cytopenia(s). The study, therefore, enrolled five pts in the first cohort. All pts received ≥ 16 weeks of systemic chemotherapy with at least stable disease per imaging prior to enrollment. None of the pts experienced DLTs. All treatment-related toxicities were expected from gem-RT, unrelated to CPI-613, and manageable. The trial is currently enrolling pts in the second cohort (CPI-613 dose of 1000 mg/m2). Conclusions: CPI-613 combined with gem-RT was safe and well tolerated at a dose of 500 mg/m2. Recruitment to the study is ongoing to determine the MTD of CPI-613 in combination with gem-RT. Table 1. Characteristic of Patients Sex Race Age ECOG Stage Prior chemotherapy Chemotherapy duration (weeks) M W 67 1 LA FFX 16 M W 64 1 LA GnP 35 M W 73 1 BR* GnP 16 M B 71 1 LA GnP 27 M W 80 1 Oligometastatic** GnP 18 * Medically inoperable ** Two lung metastases treated with stereotactic body radiation therapy (SBRT); BR: Borderline resectable; B: Black; FFX: FOLFIRINOX; GnP: Gemcitabine/Nab-paclitaxel; LA: Locally advanced. M: Male; W: White Citation Format: Mandana Kamgar, Husain Yar Khan, Amro Aboukameel, Sahar F. Bannoura, Brian Y. Chung, Aniko Szabo, Yiwei Li, Mohammed Najeeb Al Hallak, Philip A. Philip, Ben George, Kathleen K. Christians, Douglas B. Evans, Susan Tsai, Beth Erickson, John M. Goldberg, Asfar S. Azmi, William A. Hall. A phase I study of CPI-613 (devimistat) in combination with chemoradiation in patients with pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT080.

Diagnostic value of water swallow test for dysphagia in patients with head and neck cancer: A systematic review and meta-analysis.

The diagnostic efficacy of the water swallow test (WST) is relatively robust for patients with neurogenic dysphagia; however, its diagnostic performance in identifying dysphagia among patients with HNC varies across studies. Our study aims to assess the diagnostic value of the WST for detecting dysphagia in patients with HNC. Systematic retrieval of studies on the use of WST for screening dysphagia in patients with HNC from databases up to August 1, 2023. Quality assessment of the included studies was performed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Calculate the pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR, diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC) to evaluate the screening ability of WST for dysphagia. A total of seven articles, encompassing eight study groups, were included, involving the analysis of 691 patients. The meta-analysis results demonstrate that the WST has a combined sensitivity, specificity, positive LR, negative LR, DOR, and AUC for diagnosing dysphagia in patients with HNC of 0.82 (95% CI [0.64, 0.92]), 0.79 (95% CI [0.70, 0.86]), 4.00 (95% CI [2.51, 6.36]), 0.22 (95% CI [0.10, 0.50]), 17.94 (95% CI [5.56, 57.92]), and 0.86 (95% CI [0.83, 0.89]), respectively. Significant heterogeneity was observed among the included studies. Meta-regression analysis showed that the pooled sensitivity of tumor sites and treatment was closely related, while the pooled specificity of treatment and version was closely related. The subgroup analysis showed that the WST's pooled sensitivity for diagnosing dysphagia in patients with nasopharyngeal cancer was 0.40 (95% CI [0.26, 0.56]), with an AUC of 0.50, lower than in other HNC sites. The WST performed better in surgical patients than in those undergoing radiotherapy (RT) or chemoradiotherapy (CRT), with lower sensitivity, specificity, and AUC values of 0.49 (95% CI [0.36, 0.61]), 0.66 (95% CI [0.59, 0.72]), and 0.64, respectively, for RT or CRT patients. The modified WST version showed different specificity values of 0.82 (95% CI [0.75, 0.87]), compared to the regular version of 0.68 (95% CI [0.61, 0.74]). Additionally, Deek's test indicated the absence of publication bias in this study (p = 0.32). The WST demonstrates favorable sensitivity and specificity in detecting dysphagia among patients with HNC. However, the diagnostic value may vary depending on factors such as tumor sites, treatment, and the specific version of the WST used.

Total Neoadjuvant Therapy With PD-1 Blockade for High-Risk Proficient Mismatch Repair Rectal Cancer

Total neoadjuvant therapy (TNT) is the standard treatment for locally advanced rectal cancer, especially for patients with high-risk factors. However, the efficacy of TNT combined with immunotherapy for patients with proficient mismatch repair (pMMR) rectal cancer is unknown. To evaluate the safety and efficacy of TNT with induction chemoimmunotherapy followed by long-course chemoradiation in patients with high-risk, pMMR rectal cancer and to identify potential molecular biomarkers associated with treatment efficacy. This cohort study was a single-arm phase 2 trial conducted at Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, from June 2020 to October 2021. Biopsies and plasma were collected before treatment for whole-exome sequencing and cell-free DNA sequencing, respectively. Data were analyzed from May 2022 to September 2022. Participants received 3 cycles of induction oxaliplatin and capecitabine combined with camrelizumab and radiotherapy (50.6 Gy in 22 fractions) with concurrent capecitabine. Patients without disease progression received 2 cycles of consolidation oxaliplatin/capecitabine. The primary end point was pathologic complete response rate. Of 25 patients enrolled (19 men [76%]; 6 women [24%]; median [IQR] age, 58 [48-64] years), 22 patients (88%) completed the TNT schedule. The pathologic complete response rate was 33.3% (7/21). Twelve patients (48%) achieved clinical complete response, and 4 patients (16%) chose to watch and wait. R0 resection was achieved in 21 of 21 patients, and the major pathologic response rate was 38.1% (8/21). The most common adverse event was nausea (80%, 20/25); grade 3 toxic effects occurred in 9 of 25 patients (36%). Patients with tumor shrinkage of 50% or greater after induction oxaliplatin/capecitabine and camrelizumab or clinical complete response had higher percentages of LRP1B mutation. Mutation of LRP1B was associated with high tumor mutation burden and tumor neoantigen burden. Patients with high tumor mutation burden all benefited from therapy. This study found that TNT with induction chemoimmunotherapy followed by long-course chemoradiation was safe and effective for patients with high-risk rectal cancer with pMMR status. Longer follow-up and larger clinical studies are needed to validate this innovative regimen. There is also an urgent need to further validate the predictive value of LRP1B and discover other novel biomarkers with potential predictive value for rectal cancer.

NEXT: A phase 2 study of nivolumab adjuvant to chemoradiation in patients (pts) with localized urothelial carcinoma.

612 Background: Definitive chemoradiation (CRT) is the preferred bladder preservation treatment for non-metastatic urothelial cancer (nmUC). The NEXT trial (NCT03171025) evaluated the efficacy of adjuvant nivolumab to definitive CRT in pts with nmUC. Methods: This multicenter study enrolled nmUC pts who received standard-of-care CRT. Nivolumab 480 mg was administered every 4 weeks for up to 12 doses. Primary endpoint: failure-free survival (FFS) at 2 years (yrs). Secondary endpoint: safety. This is the first efficacy and safety analysis after completion of enrollment, and correlation of disease risk features, and changes in plasma cell-free DNA (cfDNA) with outcomes. Shallow whole genome sequenced data from plasma cfDNA was mapped to the human reference genome (HG19), and copy number instability (CNI) Score (Oncocyte) was derived from statistically significant altered regions. Results: From 8/03/2017 to 1/25/2023, 28 pts were enrolled. The median age was 72 yrs (range 54-86 yrs). Ten patients (36%) had ≥ T3 and/or N+ disease. At time of data cut-off (9/14/23), median nivolumab cycles were 8.5 (range 1-12), and median follow-up was 11 months (range 6 - 45). FFS at 2 yrs (n=24) was 38.7 % (95% CI 23%-65.2%). Disease relapse occurred in 16 pts, of which 9 had local recurrences. Grade ≥3 treatment-related adverse events (AEs) occurred at a frequency of 10.7%. These were elevated transaminases, diarrhea, and polymyalgia rheumatica. Grade 3 radiation therapy oncology group (RTOG) AEs occurred in 2 pts. One or more high-risk disease features (ie. plasmacytoid differentiation, T4, N+, multiple tumors, tumors > 5 cm, residual disease before CRT, CIS, and hydronephrosis) were present in 22 pts (79%). In a Cox proportional hazards model, the number of high-risk features was a significant predictor of progression (p = 0.006). Each additional high-risk feature was associated with a hazard ratio for progression of 1.77 (95% CI 1.17-2.67). Median CNI (mCNI) on C1D1 of nivolumab in relapsed pts was 31 (range 3-232) vs. 24 (range 3-109) in pts with ongoing response. The mCNI on C4D1 for pts who progressed was 15.5 (range 6-371) vs. 9 (range 3-65) in pts with ongoing response. Oncogenic gene copy number changes and the associated pathways associated with progression are listed in the table. Conclusions: Adjuvant nivolumab to CRT for nmUC has promising efficacy with tolerable AEs, even in pts with high-risk disease. Disease relapse correlates with high-risk clinical features and CNI in plasma cfDNA. Oncogenic copy number changes in genes involved in DNA repair, RTK-RAS-PI3K, WNT, and cell cycle pathways are present in cfDNA of those who progressed (Table). Clinical trial information: NCT03171025 . [Table: see text]

Comparing Methods to Determine Complete Response to Chemoradiation in Patients with Locally Advanced Cervical Cancer.

There is no consensus on the most reliable procedure to determine remission of cervical cancer after chemoradiotherapy (CRT). Therefore, this study aims to assess the diagnostic performance of two different imaging techniques, MRI and 18F[FDG]-PET/CT, in determining the presence of locoregional residual disease after CRT in patients with locally advanced cervical cancer. Patients diagnosed with locally advanced cervical cancer (FIGO 2009) treated with CRT were retrospectively identified from a regional cohort. The accuracy of MRI and 18F[FDG]-PET/CT in detecting locoregional residual disease was assessed with histology as the reference standard. The negative predictive value (NPV) and positive predictive value (PPV) for locoregional residual disease detection of MRI and 18F[FDG]-PET/CT combined were 84.2% (95% CI 73.2-92.1), and 70.4% (95% CI 51.8-85.2), respectively. The NPV and PPV of MRI alone were 80.2% (95% CI 71.2-87.5) and 47.7% (95% CI 35.8-59.7), respectively, and values of 81.1% (95% CI 72.2-88.3) and 55.8 (95% CI 42.2-68.7), respectively, were obtained for 18F[FDG]-PET/CT alone. In this study, the reliability of MRI and 18F[FDG]-PET/CT in detecting locoregional residual disease was limited. Combining MRI and 18F[FDG]-PET/CT did not improve predictive values. Routine use of both MRI and 18F[FDG]-PET/CT in the follow-up after CRT should be avoided. MRI during follow-up is the advised imaging technique. Pathology confirmation of the presence of locoregional residual disease before performing salvage surgery is warranted.

Frontal and anterior temporal hypometabolism post chemoradiation in head and neck cancer: A real-world PET study.

Adverse neurological effects after cancer therapy are common, but biomarkers to diagnose, monitor, or risk stratify patients are still not validated or used clinically. An accessible imaging method, such as fluorodeoxyglucose positron emission tomography (FDG PET) of the brain, could meet this gap and serve as a biomarker for functional brain changes. We utilized FDG PET to evaluate which brain regions are most susceptible to altered glucose metabolism after chemoradiation in patients with head and neck cancer (HNCa). Real-world FDG PET images were acquired as standard of care before and after chemoradiation for HNCa in 68 patients. Linear mixed-effects voxelwise models assessed changes after chemoradiation in cerebral glucose metabolism quantified with standardized uptake value ratio (SUVR), covarying for follow-up time and patient demographics. Voxelwise analysis revealed two large clusters of decreased glucose metabolism in the medial frontal and polar temporal cortices following chemoradiation, with decreases of approximately 5% SUVR after therapy. These findings provide evidence that standard chemoradiation for HNCa can lead to decreased neuronal glucose metabolism, contributing to literature emphasizing the vulnerability of the frontal and anterior temporal lobes, especially in HNCa, where these areas may be particularly vulnerable to indirect radiation-induced injury. FDG PET shows promise as a sensitive biomarker for assessing these changes.

Chemoradiotherapy for squamous cell carcinoma of the rectum: a retrospective propensity-score matched analysis

A lack of evidence-based data on the chemoradiotherapy (CRT) efficacy in patients with squamous cell carcinoma of the rectum (SCCR) makes further study of this topic extremely important.Aim: The aim of our research was to estimate the efficacy of CRT in patients with SCCR compared to the rectal adenocarcinoma and squamous cell carcinoma of the anal canal (SCCAC).Materials and methods: Our study was based on analysis of medical records of patients with ICD–X code C20 and ICD-O 8070 / 3, 8070 / 3.1, 80703 in a database from 2007 to 2020 obtained from the archive of Research Institute FSBI “N. N. Blokhin Cancer Research Center” of the Ministry of Health of Russia. We included patients with SCCR who received CRT as initial treatment into the experimental group. Groups with rectal adenocarcinoma and SCCAC were created using propensity-score matching 1:2 taking into account sex, age, the cN clinical stage, histological grade and tumor size. The main study endpoints were 3‑year overall survival (OS) and disease-free survival (DFS) rates, complete clinical response rate and complete clinical or pathological response rate at 6 months after CRT, local recurrence and distant metastases rates, surgery rate.Results: We included 15 patients in SCCR group and 30 patients in rectal adenocarcinoma group and SCCAC group each. There were no significant differences in parameters that could affect the prognosis. The complete clinical response was achieved in 7 (46.7 %) patients with SCCR versus 3 (10.0 %) patients with adenocarcinoma (p = 0.005) and 24 (80.0 %) patients with SCCAC (p = 0.005). The surgery rate was 26.6 % (4 patients) in SCCR group, 6.67 % (2 patients) in SCCAC group, 90 % (27 patients) in adenocarcinoma group (p < 0.001). The recurrence rate was 26.7 % (4 patients) in SCCR group versus 10.0 % (3 patients) in adenocarcinoma group (p = 0.146) and 6.7 % (2 patients) in SCCAC group (p = 0.063). The metastases rate was 26.7 % (4 patients) in SCCR group, 26.7 % (8 patients) in adenocarcinoma group (p > 0.99). In SCCAC group metastases were detected in 1 (3.3 %) patient, which was significantly different compared to the SCCR group (p = 0.019). Median follow up was 44 months. The 3‑year OS was 78.8 % in SCCR group versus 91.0 % in adenocarcinoma group (p = 0.675), and 86.3 % in SCCAC group (p = 0.953). The 3‑year OS in adenocarcinoma and SCCAC groups did not differ (p = 0.996). The 3‑year DFS was 34.7 % in SCCR group versus 55.6 % in adenocarcinoma group (p = 0.504) and 82.9 % in SCCAC group (p = 0.031). The 3‑year DFS differences in adenocarcinoma and SCCAC groups were significant (p = 0.041).Conclusions: We have obtained important data on the CRT comparative efficacy in patients with SCCR, SCCAC and rectal adenocarcinoma. The high complete clinical response rate in SCCR group makes it possible to consider the use of CRT as the main treatment method. Results of our research can be used to plan the treatment of patients with SCCR.

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.

379P Nimotuzumab in combination with chemoradiation for patients with intermediate stage and locally advanced nasopharyngeal carcinoma: A retrospective comparative analysis using 5-year real-world survival data

379P Nimotuzumab in combination with chemoradiation for patients with intermediate stage and locally advanced nasopharyngeal carcinoma: A retrospective comparative analysis using 5-year real-world survival data

Predicting Complete Response after Chemoradiation in Patients with Localized Rectal Cancer.

Current strategies for localized rectal cancer include multimodal approach with neoadjuvant treatments followed by surgery. Some patients may present complete response after chemoradiation (CRT) and possible candidates to nonoperative management. We aim to detect complete-responders only based on the pretreatment radiological information using radiomics. We retrospectively studied 44 randomly selected rectal cancer patients who underwent an MR study for rectal cancer staging and, subsequently, were treated with CRT. Median age was 66 y and 59% were females. Tumors were located in the proximal rectum in 11p, 25p in the middle and 8p in the distal. The initial TNM classification, 38p had T3 stage, 19p N1 and 17p N2. Two patients did not receive chemotherapy. Median dose: 50.4Gy (48-54Gy). One radiologist and one radiation oncologist with expertise in MR manually contoured the primary tumor using Phillips IntelliSpace Portal software. We computed a total of 1688 radiomic features from the T2w images using the pyRadiomics package. We compared several machine learning (ML) classification algorithms (linear regression (LR), gaussian processes (GP), multi-layer perceptron (MLP), support vector machines (SVM), and random forest (RF)), as well as several combinations of classifiers using the scikit-learn python module. We used a stratified 5-fold cross validation approach to assess them. The performance was assessed by calculating the average of the area under the curve (AUC) from receiver operating characteristic (ROC) curve analysis for each one of the k splits generated during cross-validation. Mean accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1-score were also computed. Pathological TNM (ypTNM): 22p had ypT0N0, 9p ypT3-4, 10p ypT2 and 9p ypN1. Tumor volume between responders and non-responders were: 26.10±16.24cc vs. 22.78±34.49cc (p = 0.68). Predictions from the classifiers showed good classification capabilities identifying ypT0N0 (i.e., AUC≥0.73±0.17) for all classifiers; however, combined classifiers demonstrated superior capabilities compared to stand-alone classifiers. Specifically, the RF-MLP, RF-GP-SVM, RF-GP-MLP and RF-GP-LR combinations showed the best results with a mean accuracy, sensitivity, specificity, PPV, NPV, and F1-score of 0.80±0.13, 0.90±0.20, 0.72±0.10, 0.71±0.12, 0.92±0.16, 0.79±0.15, with slight differences for AUC CONCLUSION: We trained a series of ML algorithms based on T2w MR imaging radiomic features and evaluated their ability to distinguish responders from non-responders. MR data have a richness of information that allows identifying the response to CRT treatment in a predictive context, especially when using combined classifiers. A validation prospective set to detect ypT0N0 is warranted. Clinical utility should be evaluated.

766P A comparative study of sequential and interdigitated brachytherapy with chemoradiation in patients of locally advanced carcinoma cervix

766P A comparative study of sequential and interdigitated brachytherapy with chemoradiation in patients of locally advanced carcinoma cervix

The efficacy of neoadjuvant chemoradiotherapy in signet ring cell carcinoma of the rectum: a retrospective propensity-score matched study

INTRODUCTION: there is a lack of information chemoradiotherapy (CRT) efficacy in signet ring cell carcinoma of the rectum (SRCCR). The aim of our research was to investigate the efficacy of preoperative CRT in patients with SRCCR.PATIENTS AND METHODS: we conducted a retrospective analysis of medical records from the archive of Research Institute FSBI “N.N. Blokhin Cancer Research Center” of the Ministry of Health of Russia and multicenter registry of the Russian Society of Specialists in Colorectal Cancer (RSSCC) from 2000 to 2020 and included in the study group patients with histologically confirmed primary SRCCR who received preoperative CRT. A control group with rectal adenocarcinoma was created using propensity-score matching from the institutional database 1:1 taking into account sex, age, tumor size, the cT and cN clinical stage. We estimated the rate of Dworak tumor regression grade 3-4, RECIST, 5-year overall survival (OS) and disease-free survival (DFS) rates.RESULTS: the study and control group included 22 patients each. The study group included 11 patients (50%) with cT3 and cT4 clinical stage. 10 (45,5%) patients had cT3 clinical stage and 12 (54,5%) patients had cT4 clinical stage in the control group (p = 0,763). The number of patients with cN1-2 clinical stage was 17 (77,3%) and 16 (72,7%) in the study and control group, respectively (p = 0,728). The rate of Dworak tumor regression grade 3–4 was 40,9% in the group of patients with SRCCR and 45,5% in the group of patients with rectal adenocarcinoma (p = 0,761).When assessed by RECIST scale, 9 (40,9%), 12 (54,5%) and 1 (4,5%) patients with SRCCR had partial tumor response, stabilization and progression, respectively. Partial response was observed in 18 (81,8%) patients and stabilization — in 4 (18,2%) patients with rectal adenocarcinoma (p = 0,018). Median followup was 58,8 months. The 5-year OS was 34% in the SRCCR group and 71,3% in the group with rectal adenocarcinoma (p = 0,024), and the 5-year PFS was 30,2% with SRCCR and 52,2% with adenocarcinoma (p = 0,115).CONCLUSIONS: CRT leads to comparable grade 3–4 tumor regression in SRCCR and rectal adenocarcinoma, but the objective response rate is lower. This histological subtype has significantly lower OS values.

P07.01.A MR-GUIDED LITT THERAPY IN PATIENTS WITH PRIMARY IRRESECTABLE GLIOBLASTOMA: A CONTROLLED, PROSPECTIVE PILOT STUDY (EMITT PILOT-STUDY)

Abstract BACKGROUND Laser interstitial thermal therapy (LITT) is growing as a minimally invasive procedure in the treatment of brain tumours, even if high-quality evidence is lacking. We aimed to assess practical feasibility of a randomized controlled trial (RCT) in patients with primary irresectable glioblastoma (nGBM) and to collect pilot data on technical feasibility and safety of LITT. METHODS Adult patients with radiologically suspected glioblastoma where the multidisciplinary tumour board advised biopsy-only with KPS ≥70 and feasible trajectories to reach ≥70% ablation were prospectively included. Patients were randomized to receive either biopsy combined with LITT or biopsy alone, followed by chemoradiation (CRT). Main endpoints were practical feasibility of RCT (inclusion rate, willingness to be randomized and ability to complete the follow-up procedures), technical feasibility (time from indication to procedure, time from procedure to CRT, duration of procedure) and safety (complications reported following the Clavien Dindo classification (CD). RESULTS A total of 15 patients with an irresectable nGBM were included in the study (5 in the control and 10 in the LITT arm). Patients were highly motivated to participate to the study and all patients completed the follow-up procedure. After including 9 patients randomization was stopped. All patients were planned within 2 weeks after indication and no delay was observed in referring patients for adjuvant CRT. One, two or three laser probes were used to reach ≥70% expected ablation. Total procedure time varied between 200-540 minutes. Two CD≥3 complications occurred in the LITT arm. CONCLUSION Our pilot data suggest an RCT investigating LITT in patients with an irresectable nGBM is feasible, with initial safety data appearing in line with that of tumour resection. As a next step, we have designed a national multicenter RCT in order to evaluate survival benefit, quality of life and cost-effectiveness of LITT in this population.

Long-term treatment outcomes of temozolomide-based chemoradiation in patients with adult-type diffuse IDH-mutant grade 2 astrocytoma

PurposeTo report the long-term outcomes in adult patients with grade 2 IDH-mutant astrocytoma treated with temozolomide (TMZ)-based chemoradiation. Methods: One hundred and three patients with histologically proven grade 2 astrocytoma received radiation therapy (RT), 50.4–54 Gy in 1.8 Gy fractions, and adjuvant TMZ up to 12 cycles. Fifty-two patients received RT at the time of tumor progression and 51 in the early postoperative period for the presence of at least one high-risk feature (age > 40 years, preoperative tumor size > 5 cm, large postoperative residual tumor, tumor crossing the midline, or presence of neurological symptoms). Overall survival (OS) and progression-free survival (PFS) were calculated from the time of diagnosis.ResultsWith a median follow-up time of 9.0 years (range, 1.3–15 years), median PFS and OS times were 9 years (95%CI, 6.6–10.3) and 11.8 years (95%CI, 9.3–13.4), respectively. Median PFS was 10.6 years in the early treatment group and 6 years in delayed treatment group (hazard ratio (HR) 0.30; 95%CI 0.16–0.59; p = 0.0005); however, OS was not significantly different between groups (12.8 vs. 10.4 years; HR 0.64; 95%CI 0.33–1.25; p = 0.23). Extent of resection, KPS, and small residual disease were associated with OS, with postoperative tumor ≤ 1 cc that emerged as the strongest independent predictor (HR: 0.27; 95%CI 0.08–0.87; p = 0.01).ConclusionsTMZ-based chemoradiation is associated with survival benefit in patients with grade 2 IDH-mutant astrocytoma. For this group of patients, chemoradiation can be deferred until time of progression in younger patients receiving extensive resection, while early treatment should be recommended in high-risk patients.

Total neoadjuvant therapy with short-course radiotherapy Versus long-course neoadjuvant chemoradiotherapy in Locally Advanced Rectal cancer, Korean trial (TV-LARK trial): study protocol of a multicentre randomized controlled trial

BackgroundFor locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT) may enhance tumour response, reduce recurrence, and improve patient compliance compared to upfront surgery. Recent studies have shown that chemoradiotherapy (CRT) followed by consolidation chemotherapy leads to higher rate of pathologic complete response (pCR) than induction chemotherapy followed by CRT. However, an optimal TNT regimen that maximise the pCR rate and minimise toxicity has not been established. Therefore, the aim of this trial was to investigate whether preoperative short-course radiotherapy followed by chemotherapy with four cycles of CAPOX can double the pCR rate compared to a standard schedule of long-course preoperative CRT in patients with LARC.MethodsThis is a multi-centre, prospective, open label, randomised controlled trial. Patients with clinical primary tumour stage 3 and higher or regional node-involved rectal cancer located within 10 cm from the anal verge were randomly assigned equally to short-course radiotherapy (25 Gy in 5 fractions over 1 week) followed by four cycles of CAPOX (intravenous oxaliplatin [130 mg/m2, once a day] on day 1 and capecitabine [1,000 mg/m2, twice a day] from days 1 to 14) (TNT) or CRT (50.4 Gy in 28 fractions over 5 weeks, concurrently with concomitant oral capecitabine 825 mg/m2 twice a day). After preoperative treatment, total mesorectal excision was performed 2–4 weeks in the TNT group and 6–10 weeks in the CRT group, followed by optional additional adjuvant chemotherapy. The primary endpoint is the pCR rate, and secondary endpoints include disease-related treatment failure, quality of life, and cost-effectiveness. Assuming a pCR rate of 28% and 15% in the TNT and CRT groups, respectively, and one-side alpha error rate of 0.025 and power of 80%, 348 patients will be enrolled considering 10% dropout rate.DiscussionThe TV-LARK trial will evaluate the superiority of employed TNT regimen against the standard CRT regimen for patients with LARC. We aimed to identify a TNT regimen that will improve the pCR rate and decrease systemic recurrence in these patients.Trial registrationCris.nih.go.kr ID: KCT0007169 (April 08, 2022). The posted information will be updated as needed to reflect the protocol amendments and study progress.

Evaluation of Response and Toxicity in Patients with Locally Advanced Rectal Cancer Treated with Neoadjuvant Chemoradiation

Purpose: To study the response after neoadjuvant chemoradiation in patients with locally advanced rectal cancer with capecitabine 825 mg/m2 daily PO bid with radiation at a dose of 45Gy/20#/4 weeks, to study the clinical profile of different patients with locally advanced rectal cancer, and to assess the toxicity of patients treated with neoadjuvant chemoradiationtherapy. Materials and Methods: A prospective observational study was conducted in 60 patients with histopathologically proven locally advanced rectal carcinoma from October 2018 to April 2020 . Neoadjuvant chemoradiation was planned with capecitabine 825 mg/m2 PO bid with radiation at a dose of 45 Gy/20#/4 weeks. Radiological response was assessed 6 weeks after treatment completion, and surgery was planned according to the response. Results: Thirty-seven patients underwent definitive surgery. Pathological complete response was observed in one patient, near complete response in seven, partial response in 27, and poor or no response in two patients. Of 37 patients who have undergone surgery, 30% of patients received sphincter preserving surgery. Radiation-induced acute skin and lower gastrointestinal tract lesions were observed. Capecitabine-induced diarrhea, hematological toxicities, and a few patients with hand foot syndrome were observed. Conclusion: In locally advanced rectal cancer, preoperative radio-chemotherapy with capecitabine improves local control and reduces the risks of acute and late toxicity compared to postoperative radiochemotherapy. Thus, preoperative radiochemotherapy with capecitabine is safe and well tolerated in locally advanced rectal cancer, especially in tumors of the lower and middle rectum.

Feasibility and Tolerability of Adjuvant Capecitabine-Based Chemoradiation in Patients With Breast Cancer and Residual Disease After Neoadjuvant Chemotherapy: A Prospective Clinical Trial

Addition of adjuvant capecitabine improves overall survival for patients with breast cancer lacking pathologic complete response to standard-of-care neoadjuvant chemotherapy. Combining radiosensitizing capecitabine concurrent with radiation may further improve disease control, although the feasibility and tolerability of chemoradiation in this setting is unknown. This study aimed to determine the feasibility of this combination. Secondary objectives included the effect of chemoradiation on physician-reported toxicity, patient-reported skin dermatitis, and patient-reported quality of life compared with patients with breast cancer treated with adjuvant radiation. Twenty patients with residual disease following standard neoadjuvant chemotherapy were enrolled in a prospective single-arm trial and treated with adjuvant capecitabine-based chemoradiation. Feasibility was defined as ≥75% of patients completing chemoradiation as planned. Toxicity was assessed using Common Terminology Criteria for Adverse Events version 5.0 and the patient-reported radiation-induced skin reaction scale. Quality of life was measured using the RAND Short-Form 36-Item Health Survey. Eighteen patients (90%) completed chemoradiation without interruption or dose reduction. The incidence of grade ≥3 radiation dermatitis was 5% (1 of 20 patients). Patient-reported radiation dermatitis did not show a clinically meaningful difference following chemoradiation (mean increase, 55 points) compared with published reports of patients with breast cancer treated with adjuvant radiation alone (mean increase, 47 points). On the other hand, patient-reported quality of life demonstrated a clinically meaningful decline at the end of chemoradiation (mean, 46; SD, 7) compared with the reference population of patients treated with adjuvant radiation alone (mean, 50; SD, 6). Adjuvant chemoradiation with capecitabine is feasible and tolerable in patients with breast cancer. Although current studies using adjuvant capecitabine for residual disease following neoadjuvant chemotherapy have specified sequential treatment of capecitabine and radiation, these results support the conduct of randomized trials in this setting to investigate the efficacy of concurrent radiation with capecitabine and provide patient-reported toxicity estimates for trial design.

Predictive value of baseline serum carbohydrate antigen 19-9 level on treatment effect of neoadjuvant chemoradiotherapy in patients with resectable and borderline resectable pancreatic cancer in two randomized trials.

Guidelines suggest that the serum carbohydrate antigen (CA19-9) level should be used when deciding on neoadjuvant treatment in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer). In patients with resectable pancreatic cancer, neoadjuvant therapy is advised when the CA19-9 level is 'markedly elevated'. This study investigated the impact of baseline CA19-9 concentration on the treatment effect of neoadjuvant chemoradiotherapy (CRT) in patients with resectable and borderline resectable pancreatic cancers. In this post hoc analysis, data were obtained from two RCTs that compared neoadjuvant CRT with upfront surgery in patients with resectable and borderline resectable pancreatic cancers. The effect of neoadjuvant treatment on overall survival was compared between patients with a serum CA19-9 level above or below 500 units/ml using the interaction test. Of 296 patients, 179 were eligible for analysis, 90 in the neoadjuvant CRT group and 89 in the upfront surgery group. Neoadjuvant CRT was associated with superior overall survival (HR 0.67, 95 per cent c.i. 0.48 to 0.94; P = 0.019). Among 127 patients (70, 9 per cent) with a low CA19-9 level, median overall survival was 23.5 months with neoadjuvant CRT and 16.3 months with upfront surgery (HR 0.63, 0.42 to 0.93). For 52 patients (29 per cent) with a high CA19-9 level, median overall survival was 15.5 months with neoadjuvant CRT and 12.9 months with upfront surgery (HR 0.82, 0.45 to 1.49). The interaction test for CA19-9 level exceeding 500 units/ml on the treatment effect of neoadjuvant CRT was not significant (P = 0.501). Baseline serum CA19-9 level defined as either high or low has prognostic value, but was not associated with the treatment effect of neoadjuvant CRT in patients with resectable and borderline resectable pancreatic cancers, in contrast with current guideline advice.