Combined Chemoradiotherapy Research Articles

Results of combined and chemoradiation treatment of patients with thoracic esophageal cancer according to the data of the regional cancer center

Background. esophageal cancer (ec) is one of the most aggressive malignancies of the gastrointestinal tract. chemoradiation therapy is the standard of care for locally advanced ec.The purpose of the study was to evaluate the efficacy of chemoradiation therapy given alone and in combination with surgery in patients with thoracic esophageal cancer.Material and Methods. From January 1, 2012 to december 31, 2021, a total of 940 patients with thoracic esophageal cancer were registered in the regional cancer registry, of which 178 patients were selected for concurrent chemoradiotherapy (CRT) at clinical stages I–III. thirty seven thoracic esophageal cancer patients who received CRT and required treatment interruption due to complications were not included in our analysis. The final analysis included 141 patients.Results. 37 (20.7 %) patients were unable to complete treatment due to intolerance and the development of severe complications of CRT. Hematological toxicity of grade 3-4 was noted in 21 patients (14.8 %). Non-hematological complications of grade 2-4 were noted in 109 patients (77.3 %). The 5-year relapse-free survival rates in patients undergoing and non-undergoing to surgery were 23.0 and 25.0 %, respectively (p=0.018). Overall 5-year survival rates were 24 and 27 %, respectively (p=0.020). The rate of pathological complete response (pcR) was 43.5 % (in 20 of 46 patients who underwent surgery after CRT). The median survival time in patients with clinical complete response (ccR) was 24.0 months and the median survival time in patients with pcR was 29.0 months. The 3-year survival rates were 21 and 45 %, respectively (p=0.050).Conclusion. The combination of chemoradiotherapy and surgery in patients with thoracic esophageal cancer demonstrated an increase in overall survival in our study. if there is a complete clinical response to CRT and contraindications for surgery or the patient’s refusal to undergo surgery, it is advisable to use the “wait & watch” tactic.

Co-occurrence of symptoms after radiochemotherapy in locally advanced cervix cancer patients: a cluster analysis

Background State of the art combined radiochemotherapy and image-guided brachytherapy for locally advanced cervical cancer (LACC) has shown improved disease control and survival as well as a significant reduction of organ related morbidity. However, LACC cancer survivors are still experiencing a spectrum of symptoms. The aim of this study was to identify co-occurring symptoms in cervix cancer survivors by using patient-reported outcome and physician assessed morbidity. Materials and method EMBRACE I is a multicenter prospective observational study with 1416 LACC patients (2008–2015). Information on physician-assessed morbidity and patient-reported outcome was assessed at baseline and at regular follow-ups up with the CTCAE v.3 and EORTC-C30/CX24, respectively. Patients with at least 2 years of follow-up were included and data from 3 months to 2 years was used in the analysis. Factor analysis was used on both EORTC and CTCAE data with symptoms and follow-ups as observations. The extracted factors represent clusters of symptoms. Subsequently, regression models were built to investigate associations between the symptom clusters and QOL. Results The analysis included 742 patients. Despite the differences in the definition of physician-assessed and patient-reported symptoms, similar clusters are identified by the two assessment methods. Three main organ-related clusters are recognized for urinary, gastro-intestinal and vaginal morbidity. Furthermore, a general symptoms cluster where fatigue, pain, insomnia, neuropathy, and hot flashes have large weights is found. Lastly, a cluster with nausea, vomit and lack of appetite is also identified. The general, gastrointestinal and nausea clusters show significant associations with general QOL. Conclusions This analysis on both PRO and physician-assessed morbidity found a cluster associated with general symptoms and organ-related symptom clusters (urinary, gastrointestinal, vaginal). This shows that LACC survivors experience a variety of co-occurring symptoms. Our analysis also shows that the cluster of general symptoms is associated with a decrease in QOL.

Indications de la chirurgie dans les cancers bronchiques non à petites cellules de stade III: Stage III non-small-cell lung cancer: surgical indications

According to the 8th TNM classification, stage III non-small-cell lung cancer (NSCLC) should be subdivided into stage IIIA which represents a heterogeneous group, and stages IIIB and IIIC. N2 involvement defines the most common stage IIIIA subgroup but also the most diverse subcategory.As for stage IIIA, an intervention may be considered for T3N1 and T4N0-1 tumours when a complete resection may be obtained, in some cases after induction therapy or followed by adjuvant therapy. Treatment of N2 involvement remains more controversial. When N2 disease is discovered incidentally during thoracotomy a resection should be performed if this can be complete. Most patients with N2 disease proven by a minimally invasive or invasive technique are treated with induction therapy followed by surgery or radiotherapy. Lobectomy may be recommended in those patients with proven media stinal downstaging after induction therapy. Patients with bulky N2 disease are mostly treated with combined chemoradiotherapy followed by immunotherapy. Immunotherapy has profoundly changed the therapeutic approach for metastatic lung cancer. Recent randomised trials have shown that immunotherapy is also an effective treatment for locally advanced stage III lung cancers, but its exact position in therapeutic algorithms including radiotherapy and/or surgery still remains to be determined.The extreme variability of stage III is at the origin of controversies that have lasted for more than 30 years. Nevertheless, the consensus requires a joint and comprehensive evaluation of the locoregional disease as well as the patient in his globality. Every patient should be discussed in a multidisciplinary team.1877-1203/© 2023 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Терморадиохимиотерапия в комбинированном лечении рака прямой кишки

Currently, the treatment of rectal cancer requires a multidisciplinary approach. So the combined method of treatment, including chemoradiotherapy and the surgical stage, has proven itself reliably. However, the desired results that significantly increase the rates of relapse-free and metastatic survival have not yet been achieved. The use of radio modifiers makes it possible to enhance radiation exposure without increasing the total focal dose. One of the universal radio modifiers is local hyperthermia. Purpose: To develop a method of thermoradiochemotherapy in the combined treatment of distal rectal cancer and evaluate its effectiveness. Material and methods: This work is based on the analysis of the results of treatment of 141 patients with morphologically confirmed locally advanced distal rectal cancer. In accordance with the objectives of the study, all patients were divided into 2 groups. In the combined treatment of 75 patients, the first stage was performed chemoradiotherapy (CLT) in combination with local hyperthermia (LH). Local hyperthermia was not used in the treatment of 66 patients. Results: Long-term results of complex treatment of patients with an independent course of chemoradiotherapy/thermochemoradiotherapy (dynamic observation group) and after surgical treatment are presented. One – year relapse-free survival in the group with an independent course of TRHT was 96.7 %, in the CLT group – 79.3 % (p=0.024). There was a significant increase in three–year relapse-free survival – 93.3 % versus 76.7 % in the control (p=0.041). Among patients who underwent surgical treatment at the second stage, the study of one-year relapse-free survival did not reveal statistical significance. Three – year relapse-free survival in patients with TRHT compared with the CLT group was 96.2 % versus 86.0 % (p=0.038). The effectiveness of thermoradiochemotherapy in patients of this category was evaluated. The tolerability of treatment in all patients is satisfactory. Among all radiation reactions, the most frequently observed phenomena of radiation epidermitis I–II art. in the projection of irradiation fields (Table 1). Acute radiation reactions were reversible and did not have a negative effect on the subsequent stages of treatment. Treatment for all patients (n=141) was implemented in full.

Development and Validation of a Recurrence-Free Survival Prediction Model for Locally Advanced Esophageal Squamous Cell Carcinoma with Neoadjuvant Chemoradiotherapy

BackgroundA recurrence-free survival (RFS) prediction model was developed and validated for patients with locally advanced esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy (NCRT) in combination with surgery.Patients and MethodsWe included 282 patients with esophageal squamous cell carcinoma who received neoadjuvant chemoradiotherapy (NCRT) combined with surgery, constructed three models incorporating pathological factors, investigated the discrimination and calibration of each model, and compared the clinical utility of each model using the net reclassification index (NRI) and the integrated discrimination index (IDI).ResultsMultivariable analysis showed that pathologic complete response (pCR) and lymph node tumor regression grading (LN–TRG) (p < 0.05) were independent prognostic factors for RFS. LASSO regression screened six correlates of LN-TRG, vascular invasion, nerve invasion, degree of differentiation, platelet grade, and a total diameter of residual cancer in lymph nodes to build model three, which was consistent in terms of efficacy in the training set and validation set. Kaplan–Meier (K–M) curves showed that all three models were able to distinguish well between high- and low-risk groups (p < 0.01). The NRI and IDI showed that the clinical utility of model 2 was slightly better than that of model 1 (p > 0.05), and model 3 was significantly better than that of model 2 (p < 0.05).ConclusionsClinical prediction models incorporating LN-TRG factors have high predictive efficacy, can help identify patients at high risk of recurrence after neoadjuvant therapy, and can be used as a supplement to the AJCC/TNM staging system while offering a scientific rationale for early postoperative intervention.

The impact of intensified staging and combined therapies in locally advanced pancreatic cancer: a secondary analysis of prospective studies.

To investigate the use of comprehensive pre-treatment staging with multiple diagnostic modalities, including functional imaging and minimally invasive surgical procedures, in locally advanced pancreatic cancer (LAPC) patients. The primary objective was to detect occult metastatic disease using staging laparoscopy and 18FFDG-PET/CT scan. The study also evaluated treatment efficacy and outcomes in LAPC patients treated with combined therapies. This study was a secondary analysis of three prospective studies of chemoradiotherapy (CRT) with or without induction chemotherapy (IC). The inclusion period was from December 2009 until February 2023. An intensified pretreatment staging was conducted for all LAPC patients. Patients without distant disease at initial staging, with borderline resectable or unresectable LAPC, were enrolled in chemoradiotherapy combination protocols (CRT with or without IC). IC regimens included GemOx or FOLFIRINOX for four cycles, followed by concurrent CRT with gemcitabine. The primary endpoint was the detection of occult metastatic disease, and secondary objectives included resection rate, treatment toxicity, overall survival (OS), progression-free survival (PFS), local control (LC), and metastasis-free survival (MFS). Out of the 134 LAPC patients, 33.5% were identified with metastatic disease. Of these, 23.1% had a positive exploratory laparoscopy. Additionally, 13.4% were identified as having distant metastases by 18-FDG PET/CT. The median PFS for all patients who completed CRT was 14.3 months, and the median OS was 17.2 months. Resected patients after the combined therapies demonstrated significantly improved outcomes compared to non-resected patients (median PFS, 22.5mo vs. 9.5mo, P<0.001; median OS, 38.2mo vs. 13mo, P<0.001). Moreover, patients treated with IC followed by CRT showed significantly better outcomes compared to upfront CRT group (median PFS, 19mo vs. 9.9mo, P<0.001; median OS, 19.3mo vs. 14.6mo, P<0.001). At univariate logistic regression analysis, the adding of IC was the only predictor for resection rate (95% CI 0.12-1.02, P=0.05), and this data was confirmed at multivariate analysis (95% CI 0.09-0.98, P=0.04). Haematological and gastrointestinal toxicities were observed during treatment, with manageable adverse events. The use of comprehensive pre-treatment staging, including laparoscopy and 18F-FDG-PET/CT scan, is an effective approach in identifying occult metastatic disease in LAPC patients. Our findings offer valuable insights into accurate staging and treatment efficacy, providing evidence-based support for optimal management strategies in LAPC patients.

Polymorphism at codon 31 of CDKN1A (p21) as a predictive factor for bevacizumab therapy in glioblastoma multiforme

Glioblastoma (GBM), a prevalent and malignant brain tumor, poses a challenge in surgical resection due to its invasive nature within the brain parenchyma. CDKN1A (p21, Waf-1), a cyclin-dependent kinase inhibitor, plays a pivotal role in regulating cell growth arrest, terminal differentiation, and apoptosis. The existence of natural variants of CDKN1A has been associated with specific cancer types. In this retrospective study, our objective was to identify polymorphic variants of CDKN1A, specifically c.93C > A (codon 31 Ser31Arg), and investigate its potential impact within the scope of bevacizumab therapy for glioblastoma multiforme. This study involved a cohort of 139 unrelated adult Chinese GBM patients in Taiwan. Genomic DNA extracted from tumor samples was utilized for genotyping using the polymerase chain reaction (PCR) restriction fragment length polymorphism method (PCR–RFLP analysis). Through unconditional logistic regression analysis, odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. Our findings unveiled that among these GBM patients, the distribution of codon 31 polymorphisms was as follows: 23.02% were Serine homozygotes (Ser/Ser), 27.34% were Arginine homozygotes (Arg/Arg), and 49.64% were Serine/Arginine heterozygotes (Ser/Arg). While CDKN1A c.93C > A polymorphisms did not exhibit a direct association with overall survival in GBM patients, noteworthy survival benefits emerged among individuals with Arg/Arg and Arg/Ser genotypes who received combined concurrent chemoradiotherapy (CCRT) and bevacizumab treatment compared to those who underwent CCRT alone. Our findings indicate a significant involvement of the CDKN1A c.93C > A polymorphism in the development and onset of GBM, offering potential implications for the early prognostication of bevacizumab therapy outcomes.

Cell-type specific anti-cancerous effects of nitro-oleic acid and its combination with gamma irradiation.

Nitro-fatty acids (NFAs) are endogenous lipid mediators capable of post-translational modifications of selected regulatory proteins. Here, we investigated the anti-cancerous effects of nitro-oleic acid (NO2OA) and its combination with gamma irradiation on different cancer cell lines. The effects of NO2OA on cell death, cell cycle distribution, or expression of p21 and cyclin D1 proteins were analyzed in cancer (A-549, HT-29 and FaDu) or normal cell lines (HGF, HFF-1). Dose enhancement ratio at 50 % survival fraction (DERIC50) was calculated for samples pre-treated with NO2OA followed by gamma irradiation. NO2OA suppressed viability and induced apoptotic cell death. These effects were cell line specific but not in general selective for cancer cells. HT-29 cell line exerted higher sensitivity toward NO2OA treatment among cancer cell lines tested: induction of cell cycle arrest in the G2/M phase was associated with an increase in p21 and a decrease in cyclin D1 expression. Pre-treatment of HT-29 cells with NO2OA prior irradiation showed a significantly increased DERIC50, demonstrating radiosensitizing effects. In conclusion, NO2OA exhibited potential for combined chemoradiotherapy. Our results encourage the development of new NFAs with improved features for cancer chemoradiation.

REHABILITATION STRATEGIES FOLLOWING ENDOMETRIAL CANCER TREATMENT: EXPLORING CONTEMPORARY APPROACHES AND MANAGEMENT ISSUES

The incidence of oncogynecological pathologies, including endometrial cancer (EC), tends to increase, especially among women of reproductive age. Treatment of EC involves radical surgical intervention, as well as combined chemoradiotherapy according to indications, which has a traumatic effect on the physical, psycho-emotional, and social well-being of the patient. A comprehensive personalized rehabilitation program significantly improves the quality of life (QoL). However, the issue of introducing restorative measures into еру clinical practice remains open.

Sellar atypical teratoid/rhabdoid tumor in adults: survival analysis of treatment strategies. Illustrative case.

Atypical teratoid/rhabdoid tumor (ATRT) is a rare, highly aggressive central nervous system tumor predominantly found in children. Limited information exists on ATRT in adults, posing challenges in diagnosis and treatment. This study presents the case of an adult patient with ATRT in the sellar region and explores the impact of different treatment regimens on patient survival. A 60-year-old female with an ATRT underwent resection of the tumor, followed by adjuvant chemoradiotherapy. Molecular genetic analysis revealed compound heterozygous SMARCB1 point mutations. Survival analysis was performed on previously published adult ATRT cases, comparing treatment approaches. The cohort's overall median survival was 6 months, with patients receiving combined chemoradiotherapy showing the longest median survival of 23.5 months. Statistical analysis demonstrated a significant difference in survival between patients treated with surgery alone and those receiving surgery followed by chemoradiotherapy (p < 0.001). However, no significant difference was observed between patients treated with surgery alone and those with postoperative radiotherapy (p = 0.105). Early initiation of adjuvant chemoradiotherapy following surgery improves survival outcomes in adult patients with ATRT. Because of limited data on standardized treatment protocols for adults with ATRT, further research and larger-scale studies are needed to establish effective treatment guidelines for this population.

Survival outcomes of anal adenocarcinoma versus rectal adenocarcinoma: A retrospective cohort study.

Anal adenocarcinoma(AA) is a rare malignancy with decreased survival compared to rectal adenocarcinoma (RA). However, AA continues to be treated with similar algorithms compared to rectal cancer with minimal data regarding the efficacy of these treatment algorithms. A retrospective chart review of patients with non-metastatic AA at a single tertiary-care institution from 1995 to 2020. This cohort was matched 2:1 to a group of RA patients for comparison. The primary outcome of interest was overall survival rates. Sixteen patients with stages I-III AA were matched to a cohort of RA. There were no significant differences between the cohorts with regard to patient demographics, comorbidities, disease stage or histologic features. There were also no significant differences in treatment modalities between the two cohorts with amajority undergoing multimodal therapy with chemoradiation and surgery. All patients with AA demonstrated significantly worse survival than all patients with rectal adenocarcinoma (five-year survival 47.7% vs. 82.3%, respectively. p < 0.05). When looking at a sub-group of patients who underwent combination chemoradiation and surgery from each cohort, anal adenocarcinoma continued to exhibit lower overall survival (five-year survival 41.6% and 86.4%, respectively. p < 0.05). In a multi-variable model that adjusted for location, American Joint Committee on Cancer (AJCC) stage and treatment pathway, tumor location in the anal canal was an independent predictor of overall survival (Hazard ratio [HR] 2.7, p < 0.05). AA has worse survival as compared to RA despite similar treatment. This study highlights the need to evaluate the current classification and treatment pathways to improve outcomes.

Locally advanced cervical cancer: how the improvement in techniques in external beam radiotherapy and brachytherapy impacts on survival outcomes and long-term toxicities.

Platinum-based chemoradiotherapy and brachytherapy are the standard treatment for locally advanced cervical cancer. Reported long-term outcomes for treated with both IMRT and 3D-Image-guided-adaptive brachytherapy are lacking. This retrospective study included 165 patients with FIGO Stage IB-IVB cervical cancer, treated with chemoradiotherapy in combination with brachytherapy. External beam radiotherapy was delivered as IMRT/VMAT/TOMO helical or 3DCRT. The intracavitary brachytherapy treatment (ICBT) was performed using two different planning system (with or without optimization). Among the patient subgroups, comprising those who received IMRT/VMAT/Tomo helical and 3DCRT, as well as those who underwent ICBT planning optimization and those who did not, homogeneity was observed in terms of age, performance status, T stage, N status, TNM stage, and histology. With a median follow-up time of 60.5months, the 5-year overall survival (OS) in the 3DCRT and IMRT groups was 74.9% and 92.8%, respectively (p = 0.033). The 5-year OS in the ICBT planning optimization group was 93.7%, compared to 75% in the non-optimization group (p = 0.014). Regarding late radiation toxicities, patients in the IMRT group had a lower incidence of chronic rectal toxicity compared to those in the 3DCRT group (6.5% vs. 34.1%, p = 0.001). The group with ICBT planning optimization had a lower incidence of late urinary toxicities (10.4%) compared to the non-optimized ICBT planning group (18.2%, p = 0.012). Similarly, the ICBT planning optimization group had a lower incidence of late rectal toxicity (6.5% with 80% grade 1 and 20% grade 2) compared to the non-optimized ICBT planning group (34.1%, p = 0.001). In this series, the group of patients receiving optimized ICBT had an advantage in terms of OS and CSS suggesting that the use of new Treatment Planning Systems associated with 3D imaging, improves the long-term survival. Additionally, a significant reduction in late rectal and urinary toxicity has been observed.

Matching between Clinical and Dosimetric Results in Comparing Intensity Modulated Radiotherapy with Three-Dimensional Conformal Radiotherapy in Locally Advanced Lung Cancer

Background Radiation therapy plays an essential role in the treatment of locally advanced lung cancer, but it inevitably leads to incidental and unnecessary dose to critical organs, including the lung, heart, and esophagus. Objective A dosimetric study to compare 3D CRT to IMRT in locally advanced lung cancer as regards normal tissue irradiation and target coverage using COSI &amp; modified COSI indices, DVH, homogeneity index, conformity index, target coverage index. Also to evaluate acute and late toxicity of esophagus, heart and lung in three-dimensional conformal radiotherapy and intensity modulated radiotherapy, in patients with locally advanced lung cancer who received definitive concurrent chemo-radiation or sequential chemo-radiation according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Patients and Methods 20 patients were selected to participate in our retrospective study from 2014 till 2019. They were recruited from bronchogenic cancer clinic, clinical oncology department in Ain Shams University Hospitals using a convenient sampling method. Diagnosis of NSCLC or SCLC was confirmed histologically and further radiological assessment for TNM staging was performed. All patients where 18 years old or older and were prescribed for either combined or sequential chemoradiotherapy for treatment of locally invasive lung cancer with ECOG PS equal or less than 2. They received 3D CRT of total 60 Gy. On the same CT contour defined for 3D CRT another plan was done for IMRT by computer based inverse planning with specific dose constrains to surrounding organs. Results In our study IMRT technique helped in sparing doses delivered to heart, lung &amp; esophagus in comparison with 3D CRT, but it was statistically significant for the lung only with p-value = 0.003. As regard the dosimetric indices IMRT showed better target coverage, dose homogenity &amp; dose conformity in comaparison with 3D CRT, but it was statistically significant for CI with p-value= 0.028. Using the COSI &amp; mCOSI also was in favor of IMRT but it was stastistically significant in mCOSI with pvalue=0.023 Conclusion IMRT showed superior outcomes as regards delivered doses (both to target and at-risk organs) compared to the conventional 3D CRT achieving the main purpose for patients with locally advanced lung cancer receiving chemoradiothrapy which is better target volume coverage and less unnecessary dose to at-risk nearby vital organs. As IMRT spares OAR it’s expected that clinical toxicity noticed with 3DCRT will be less thus, more tolerability to CCRT.

Phase I / II trial of metformin as a chemo-radiosensitizer in a head and neck cancer patient population

ObjectivesRetrospective studies have shown that head and neck squamous cell carcinoma (HNSCC) patients taking metformin demonstrate superior survival compared to their counterparts. We sought to determine whether metformin combined with chemoradiation would improve HNSCC patient survival compared to historical controls. Materials and methodsWe conducted a Phase I/II prospective, single arm clinical trial in patients with newly diagnosed HNSCC (NCT02949700). Patients received platinum-based chemoradiation in combination with orally dosed metformin at one of 2 doses- 850 mg BID or 1500 mg BID administered during radiation, with a 2-week lead-in phase. Toxicity, disease response and survival metrics were ascertained throughout the study period. ResultsA total of 25 patients were evaluable for toxicity and survival; 9 failed to reach the predetermined 70% compliance with the study drug. No dose limiting toxicities were identified in the Phase I component and there were no grade 4 adverse events likely related to metformin throughout the study. The primary outcome for the Phase II component was met with a response rate of 96%. Three-year overall survival was ∼70% in the per protocol p16 + cohort and 0% in the per protocol p16- cohort. Survival among participants with a ≥70% metformin compliance to <70% metformin compliance demonstrated a trend towards improvement in the ≥70% compliance cohort, though this did not reach significance. ConclusionMetformin is well tolerated during concurrent chemoradiation for HNSCC. Its effectiveness as a chemo-radiosensitizer remains unclear and will require further study with randomized controlled clinical trials in this patient population.

Comparison of carcinosarcoma and adenocarcinoma of the gallbladder: a study based on SEER population for propensity matching and nomogram analysis.

Carcinosarcoma of the gallbladder (CSGB) is an uncommon malignancy, and limited literature is available on its clinicopathological features, prognosis, and treatment options. Using the SEER database, we selected 7634 gallbladder adenocarcinoma patients (diagnosed from 2004 to 2015) and 58 carcinosarcoma of the gallbladder patients (diagnosed from 1988 to 2019) based on predetermined criteria. We compared the overall survival (OS) and cancer-specific survival (CSS) before and after propensity score matching in two groups. Cox univariate and multivariate analyses were performed, and a nomogram was further generated to investigate the impact of clinical and pathological variables on the survival of patients with CSGB. Finally, we evaluated the effect of different treatment modalities on the overall survival of CSGB patients. Notably, CSGB patients had larger tumors and underwent surgery more frequently than gallbladder adenocarcinoma patients, with lower rates of deeper tumor infiltrates, and lymph node infiltrates. Conversely, gallbladder adenocarcinoma patients had a higher proportion of AJCC staging (III-IV). Despite these differences, no significant differences were found in OS and CSS between the two groups before and after propensity score matching. For CSGB patients, AJCC staging, surgery and tumor size were significant prognostic factors, while treatment modalities such as surgery combined with chemotherapy, or combined radiochemotherapy, as well as radical resection, did not significantly prolong patient survival. No significant difference was found in survival rates between CSGB and gallbladder adenocarcinoma patients, while radical surgery and different combined treatment modalities did not provide significant survival benefits.

Modulation of PD‑L1 expression by standard therapy in head and neck cancer cell lines and exosomes.

Although checkpoint inhibitors (CPI) have recently extended the treatment options and improved clinical response of advanced stage head and neck squamous cell carcinoma (HNSCC), treatment success remains unpredictable. Programmed cell death ligand‑1 (PD‑L1) is a key player in immunotherapy. Tumor cells, and exosomes derived therefrom, are carriers of PD‑L1 and efficiently suppress immune responses. The aim of the present study was to analyze the influence of established therapies on PD‑L1 expression of HNSCC cell lines and their exosomes. The HNSCC cell lines, UM‑SCC‑11B, UM‑SCC‑14C and UM‑SCC‑22C were treated with fractionated radiotherapy (RT; 5x2Gy), cisplatin (CT) and cetuximab (Cetux) as monotherapy, or combined therapy, chemoradiotherapy (CRT; RT and CT) or radioimmunotherapy (RT and Cetux). The expression of PD‑L1 and phosphorylated (p)ERK1/2 as a mediator of radioresistance were assessed using western blotting, immunohistochemistry and an exvivo vital tissue culture model. Additionally, exosomes were isolated from concentrated supernatants of the (un‑)treated HNSCC cell lines by size exclusion chromatography. Exosomal protein expression levels of PD‑L1 were detected using western blotting and semi‑quantitative levels were calculated. The functional impact of exosomes from the (un‑)treated HNSCC cell lines on the proliferation (MTS assay) and apoptosis (Caspase 3/7 assay) of the untreated HNSCC cell lines were measured and compared. The HNSCC cell lines UM‑SCC‑11B and UM‑SCC‑22B showed strong expression of pERK1/2 and PD‑L1, respectively. RT upregulated the PD‑L1 expression in UM‑SCC‑11B and UM‑SCC‑14C and in exosomes from all three cell lines. CT alone induced PD‑L1 expression in all cell lines. CRT induced the expression of PD‑L1 in all HNSCC cell lines and exosomes from UM‑SCC‑14C and UM‑SCC‑22B. The data indicated a potential co‑regulation of PD‑L1 and activated ERK1/2, most evident in UM‑SCC‑14C. Exosomes from irradiated UM‑SCC‑14C cells protected the unirradiated cells from apoptosis by Caspase 3/7 downregulation. The present study suggested a tumor cell‑mediated regulation of PD‑L1 upon platinum‑based CRT in HNSCC and in exosomes. A co‑regulation of PD‑L1 and MAPK signaling response was hypothesized.

Trends in use of radiation therapy, chemotherapy, and combination chemoradiotherapy in advanced uterine cancer before, during, and after GOG 258

ObjectiveTo explore the use of Gynecologic Oncology Group 258 (GOG 258) study regimens before, during, and after the study.MethodsPatients aged 18 years or older with endometrial cancer between 2004–2019 were...

Pneumonitis After Concurrent Chemoradiation and Immune Checkpoint Inhibition in Patients with Locally Advanced Non-small Cell Lung Cancer

AimsPneumonitis is a common and potentially deadly complication of combined chemoradiation and immune checkpoint inhibition (CRT-ICI) in patients with locally advanced non-small cell lung cancer (LA-NSCLC). In this study we sought to identify the risk factors for pneumonitis with CRT-ICI therapy in LA-NSCLC cases and determine its impact on survival. Materials and methodsWe conducted a retrospective chart review of 140 patients with LA-NSCLC who underwent curative-intent CRT-ICI with durvalumab between 2018 and 2021. Pneumonitis was diagnosed by a multidisciplinary team of clinical experts. We used multivariable cause-specific hazard models to identify risk factors associated with grade ≥2 pneumonitis. We constructed multivariable Cox proportional hazard models to investigate the impact of pneumonitis on all-cause mortality. ResultsThe median age of the cohort was 67 years; most patients were current or former smokers (86%). The cumulative incidence of grade ≥2 pneumonitis was 23%. Among survivors, 25/28 patients had persistent parenchymal scarring. In multivariable analyses, the mean lung dose (hazard ratio 1.14 per Gy, 95% confidence interval 1.03–1.25) and interstitial lung disease (hazard ratio 3.8, 95% confidence interval 1.3–11.0) increased the risk for pneumonitis. In adjusted models, grade ≥2 pneumonitis (hazard ratio 2.5, 95% confidence interval 1.0–6.2, P = 0.049) and high-grade (≥3) pneumonitis (hazard ratio 8.3, 95% confidence interval 3.0–23.0, P < 0.001) were associated with higher all-cause mortality. ConclusionsRisk factors for pneumonitis in LA-NSCLC patients undergoing CRT-ICI include the mean radiation dose to the lung and pre-treatment interstitial lung disease. Although most cases are not fatal, pneumonitis in this setting is associated with markedly increased mortality.

Treatment of primary or recurrent non-resectable pancreatic cancer with proton beam irradiation combined with gemcitabine-based chemotherapy.

Pancreatic cancer accounts for around 4.6% of cancers deaths worldwide per year. Despite many advances in treatment regimes, the prognosis is still poor. Only 20% of tumors are primarily resectable. Recurrences-both with distant metastasis as well as locoregional-are frequent. For patients with primary nonresectable localized disease or localized recurrences, we offered chemoradiation to achieve local control over along period of time. We here report our results on combined chemoradiation of pancreatic tumors and local recurrences using proton beam therapy. We report on 25patients with localized nonresectable pancreatic cancer (15patients) or local recurrent disease (10patients). All patients were treated with combined proton radiochemotherapy. Overall survival, progression-free survival, local control, and treatment-related toxicity were analyzed using statistically methods. Median RT dose was 54.0 Gy (RBE) for proton irradiation. The toxicity of treatment was acceptable. Four CTCAE gradeIII and IV adverse events (bone marrow disfunction, gastrointestinal [GI] disorders, stent dislocation, myocardial infarction) were recorded during or directly after the end of radiotherapy; two of them were related to combined chemoradiation (bone marrow disfunction, GI disorders). Six weeks after radiotherapy, one additional gradeIV toxicity was reported (ileus, caused by peritoneal carcinomatosis, not treatment related). The median progression-free survival was 5.9months and median overall survival was 11.0months. The pretherapy CA19‑9 level was astatistically significant prognostic factor for enhanced overall survival. Local control at 6months and 12months were determined to be 86% and 80%, respectively. Combined proton chemoradiation leads to high local control rates. Unfortunately, PFS and OS are driven by distant metastasis and were not improved compared to historical data and reports. With this in mind, enhanced chemotherapeutical regimes, in combination with local irradiation, should be evaluated.

A phase I study of the Wee1 kinase inhibitor adavosertib (AZD1775) in combination with chemoradiation in cervical, upper vaginal, and uterine cancers

ObjectiveWee1 kinase is a crucial regulator of the G2/M checkpoint which prevents entry of damaged DNA into mitosis. Adavosertib (AZD1775), a selective inhibitor of Wee1, induces G2 escape and increases...