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Background: Glioblastoma (GBM) is a poor prognosis grade 4 glioma. After surgical resection, the standard therapy consists of concurrent radiotherapy (RT) and temozolomide (TMZ) followed by TMZ alone. Our previous data on melanoma patients showed that Dendritic Cell vaccination (DCvax) could increase the amount of intratumoral-activated cytotoxic T lymphocytes. Methods: This is a single-arm, monocentric, phase II trial in two steps according to Simon's design. The trial aims to evaluate progression-free survival (PFS) at three months and the safety of a DCvax integrated with standard therapy in resected GBM patients. DCvax administration begins after completion of RTCTwith weekly administrations for 4 weeks, then is alternated monthly with TMZ cycles. The primary endpoints are PFS at three months and safety. One of the secondary objectives is to evaluate the immune response both in vitro and in vivo (DTH skin test). Results: By December 2022, the first pre-planned step of the study was concluded with the enrollment, treatment and follow up of 9 evaluable patients. Two patients had progressed within three months after leukapheresis, but none had experienced DCvax-related G3-4 toxicities Five patients experienced a positive DTH test towards KLH and one of these also towards Frontiers autologous tumor homogenate. The median PFS from leukapheresis was 11.3 months and 12.2 months from surgery. Conclusions: This combination therapy is well-tolerated, and the two endpoints required for the first step have been achieved. Therefore, the study will proceed to enroll the remaining 19 patients. [ABSTRACT FROM AUTHOR]

Objective: The optimal management of rectal cancer remains a subject of ongoing research. This meta-analysis of individual patient data assessed the benefit of chemoradiotherapy (fluorouracil-based) in local advanced rectal cancer: disease-free survival and overall survival. Methods: We pooled the data of 6145 patients from 24 studies of rectal cancer who received neoadjuvant radiotherapy with concomitant fluorouracil or capecitabine and surgery. The PRISMA 2020 abstract checklist was followed. Individual participant survival was reconstructed with an algorithm from published Kaplan–Meier curves. Results: The median OS was not reached; the mean survival time was 135.4 months (127.9–141.5). The median DFS was 176.9 months, and the mean disease-free survival time was 122.6 months (111.7–131.9). Conclusions: We provided a benchmark for future studies on rectal cancer treatment. The present results can be used in decision-making for locally advanced rectal cancer patients. [ABSTRACT FROM AUTHOR]

Background/Objectives: The objective of this study was to assess the connection between the systemic inflammation response index (SIRI) values and failure patterns of patients with IDH wild-type glioblastoma (GB) who underwent radiotherapy (RT) with FLAIR-based gross tumor volume (GTV) delineation. Methods: Seventy-one patients who received RT at a dose of 60 Gy to the GTV and 50 Gy to the clinical target volume (CTV) and had documented recurrence were retrospectively analyzed. Each patient's maximum distance of recurrence (MDR) from the GTV was documented in whichever plane it extended the farthest. The failure patterns were described as intra-GTV, in-CTV/out-GTV, distant, and intra-GTV and distant. For analytical purposes, the failure pattern was categorized into two groups, namely Group 1, intra-GTV or in-CTV/out-GTV, and Group 2, distant or intra-GTV and distant. The SIRI was calculated before surgery and corticosteroid administration. A receiver operating characteristic (ROC) curve analysis was used to determine the optimal SIRI cut-off that distinguishes between the different failure patterns. Results: Failure occurred as follows: intra-GTV in 40 (56.3%), in-CTV/out-GTV in 4 (5.6%), distant in 18 (25.4%), and intra-GTV + distant in 9 (12.7%) patients. The mean MDR was 13.5 mm, and recurrent lesions extended beyond 15 mm in only seven patients. Patients with an SIRI score ≥ 3 demonstrated a significantly higher incidence of Group 1 failure patterns than their counterparts with an SIRI score < 3 (74.3% vs. 50.0%; p = 0.035). Conclusions: The present results show that using the SIRI with a cut-off value of ≥3 significantly predicts failure patterns. Additionally, the margin for the GTV can be safely reduced to 15 mm when using FLAIR-based target delineation in patients with GB. [ABSTRACT FROM AUTHOR]

Chalcogens are used as sensitive redox‐responsive reagents in tumor therapy. However, chalcogen bonds triggered by external ionizing radiation, rather than by internal environmental stimuli, enable site‐directed and real‐time drug degradation in target lesions. This approach helps to bypass chemoresistance and global systemic toxicity, presenting a significant advancement over traditional chemoradiotherapy. In this study, we fabricated a hybrid monodisperse organosilica nanoprodrug based on homonuclear single bonds (disulfide bonds (S−S, approximately 240 kJ/mol), diselenium bonds (Se−Se, approximately 172 kJ/mol), and tellurium bonds (Te−Te, 126 kJ/mol)), including ditelluride‐bond‐bridged MONs (DTeMSNs), diselenide‐bond‐bridged MONs (DSeMSNs) and disulfide‐bond‐bridged MONs (DSMSNs). The results demonstrated that differences in electronegativities and atomic radii influenced their oxidation sensitivities and reactivities. Tellurium, with the lowest electronegativity, showed the highest sensitivity, followed by selenium and sulfur. DTeMSNs exhibited highly responsive cleavage upon exposure to X‐rays, resulting in oxidation to TeO32−. Furthermore, chalcogen‐hybridized organosilica was loaded with manganese ions (Mn2+) to enhance the release of Mn2+ during radiotherapy, thereby activating the the stimulator of interferon genes (STING) pathway and enhancing the tumor immune response to inhibit tumor growth. This investigation of hybrid organosilica deepens our understanding of chalcogens response characteristics to radiotherapy and enriches the design principles for nanomedicine based on prodrugs. [ABSTRACT FROM AUTHOR]

Sustained angiogenesis stands as a hallmark of cancer. The intricate vascular tumor microenvironment fuels cancer progression and metastasis, fosters therapy resistance, and facilitates immune evasion. Therapeutic strategies targeting tumor vasculature have emerged as transformative for cancer treatment, encompassing anti-angiogenesis, vessel normalization, and endothelial reprogramming. Growing evidence suggests the dynamic regulation of tumor angiogenesis by infiltrating myeloid cells, such as macrophages, myeloid-derived suppressor cells (MDSCs), and neutrophils. Understanding these regulatory mechanisms is pivotal in paving the way for successful vasculature-targeted cancer treatments. Therapeutic interventions aimed to disrupt myeloid cell-mediated tumor angiogenesis may reshape tumor microenvironment and overcome tumor resistance to radio/chemotherapy and immunotherapy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate clinical results and long-term patient-reported outcome measures (PROMs) on quality of life in cervical cancer patients following radiochemotherapy (RCT) and brachytherapy (BT) as definitive treatment. Materials and methods: Between 2003 and 2023, a total of 132 patients with advanced cervical cancer were evaluated for possible treatment. Patients treated by postoperative RCT, palliative radiotherapy, and those treated for recurrent disease were excluded. Thus, 46 patients receiving standard RCT and BT as their curative treatment were included in this study. PROMs were assessed prospectively by patients' self-completion of the EORTC-QLQ-C30 and EORTC-QLQ-CX24 questionnaires. Results: Five-year overall survival (OS), distant metastases-free survival (DMFS), and pelvic tumor-free survival rates (PTFS) were 53%, 54%, and 83%, respectively. A significant impact on OS was seen for FIGO (International Federation of Gynecologic Oncology) stage (IIB–IIIA: 79% vs. IIIB–IVA: 33%, p = 0.015), for overall treatment time (OTT; 50–65 d: 64% vs. > 65 d: 38%, p = 0.004), and for rectal D2cc (≤ 73 Gy: 50% vs. > 73 Gy: 38%, p = 0.046). The identical parameters were significantly associated with DMFS (FIGO stage: p = 0.012, OTT: p = 0.008, D2cc: p = 0.024). No parameters with a significant influence on PTFS were seen. In multivariate analysis, an impact of FIGO stage on OS (p = 0.05) and DMFS (p = 0.014) was detected, and of rectal D2cc on DMFS (p = 0.031). The overall QoL score was 63/100. Cognitive function was the least impaired (84/100), while role functioning was the worst (67/100). On the symptom scale, insomnia (46/100), fatigue (41/100), dyspnea (32/100), pain (26/100), and financial difficulties (25/100) were scored the worst. According to EORTC-QLQ-CX24, peripheral neuropathy (36/100) and lymphedema (32/100) occurred most frequently. Impaired sexual/vaginal functioning (32/100) and body image (22/100) were also frequently recorded. Conclusion: In patients with advanced cervical cancer, a combination of RCT and BT remains an excellent treatment option. In terms of patient-reported long-term quality of life, specific support is needed to alleviate symptoms including lymphedema, peripheral neuropathy, and impaired sexual activity. [ABSTRACT FROM AUTHOR]

Despite the advancements made in oncology in recent years, the treatment of pancreatic cancer remains a challenge. Five-year survival rates for this cancer do not exceed 10%. Among the reasons contributing to poor treatment outcomes are the oligosymptomatic course of the tumor, diagnostic difficulties due to the anatomical location of the organ, and the unique biological features of pancreatic cancer. The mainstay of treatment for resectable cancer is surgery and adjuvant chemotherapy. For unresectable and metastatic cancers, chemotherapy remains the primary method of treatment. At the same time, for about thirty years, there have been attempts to improve treatment outcomes by using radiotherapy combined with systemic treatment. Unlike chemotherapy, radiotherapy has no established place in the treatment of pancreatic cancer. This paper addresses the topic of radiotherapy in pancreatic cancer as a valuable method that can improve treatment outcomes alongside chemotherapy.

Introduction: Larynx organ preservation (LOP) in locoregional-advanced laryngeal and hypopharyngeal squamous cell carcinoma (LA-LHSCC) being only R0-resectable (clear margins > 5 mm) by total laryngectomy (TL) is desirable. Based on tumor-specific survival (TSS) and overall survival (OS) data from the RTOG 91-11 trial and meta-analyses of randomized clinical trials (RCTs), cisplatin-based concurrent radiochemotherapy (CRT) is discussed being superior to cisplatin-based induction chemotherapy followed by radiotherapy (IC+RT) and TL followed by postoperative RT (TL+PORT) or radiochemotherapy (TL+PORCT). Outside of RCTs, T4 LHSCC treated with TL+PORCT demonstrated improved OS and TSS compared to CRT alone; comparisons with docetaxel plus cisplatin (TP)-based IC+RT are unpublished. Head-to-head comparisons in RCTs of these four alternatives are missing. Materials and Methods: We utilized monocentric registry data to compare the outcome in the LOP trial DeLOS-II (NCT00508664) and propensity score (PS)- matched LHSCC patients. DeLOS-II utilized endoscopic tumor staging after one cycle of TP-based IC for selecting TL+R(C)T for non-responders versus IC+RT for responders. Main risk factors for survival (localization hypopharynx, T4, N+, tobacco smoking >30 pack years, alcohol consumption >60 g/day, age, sex) were used to calculate the individual PS for each DeLOS-II patient and 330 LHSCC patients suitable for DeLOS-II according to eligibility criteria in Leipzig by CRT (78), TL+PORT (148), and TL+PORCT (104). We performed PS matching with caliper width 0.2. Results: The 52 DeLOS-II patients (whole intent-to-treat cohort) and three PSmatched cohorts (52 LHSCC patients each) had equal distribution regarding risk factors including Charlson comorbidity score (CS; all p > 0.05) but differed in outcome. During 12,498.6 months of follow-up, 162 deaths (36/41/43/42 in DeLOS-II/TL+PORCT/TL+PORT/CRT, p = 0.356) occurred; DeLOS-II patients had superior OS and TSS. Compared to DeLOS-II, the HR (95% CI) observed in TL+PORCT, TL+PORT, and CRT for OS and TSS were 1.49 (0.92-2.43), 1.49 (1.15-3.18), and 1.81 (1.11-2.96) for OS; and 2.07 (0.944-4.58), 3.02 (1.32-6.89), and 3.40 (1.58-7.31) for TSS. Conclusion: In addition potential LOP, LA-LHSCC suitable for LOP according the DeLOS-II protocol may achieve improved survival. [ABSTRACT FROM AUTHOR]

Despite the advancements made in oncology in recent years, the treatment of pancreatic cancer remains a challenge. Five-year survival rates for this cancer do not exceed 10%. Among the reasons contributing to poor treatment outcomes are the oligosymptomatic course of the tumor, diagnostic difficulties due to the anatomical location of the organ, and the unique biological features of pancreatic cancer. The mainstay of treatment for resectable cancer is surgery and adjuvant chemotherapy. For unresectable and metastatic cancers, chemotherapy remains the primary method of treatment. At the same time, for about thirty years, there have been attempts to improve treatment outcomes by using radiotherapy combined with systemic treatment. Unlike chemotherapy, radiotherapy has no established place in the treatment of pancreatic cancer. This paper addresses the topic of radiotherapy in pancreatic cancer as a valuable method that can improve treatment outcomes alongside chemotherapy. [ABSTRACT FROM AUTHOR]

Background Patients with head and neck cancer present particularly considerable levels of emotional distress. However, the actual rates of clinically relevant mental health symptoms and disorders among this population remain unknown. Methods A Preferred Reporting Items for Systematic Review and Meta-Analyses and Meta-analyses of Observational Studies in Epidemiology–compliant systematic review and quantitative random-effects meta-analysis was performed to determine suicide incidence and the prevalence of depression, anxiety, distress, posttraumatic stress, and insomnia in this population. MEDLINE, Web of Science, Cochrane Central Register, KCI Korean Journal database, SciELO, Russian Science Citation Index, and Ovid-PsycINFO databases were searched from database inception to August 1, 2023 (PROSPERO: CRD42023441432). Subgroup analyses and meta-regressions were performed to investigate the effect of clinical, therapeutical, and methodological factors. Results A total of 208 studies (n = 654 413; median age = 60.7 years; 25.5% women) were identified. Among the patients, 19.5% reported depressive symptoms (95% confidence interval [CI] = 17% to 21%), 17.8% anxiety symptoms (95% CI = 14% to 21%), 34.3% distress (95% CI = 29% to 39%), 17.7% posttraumatic symptoms (95% CI = 6% to 41%), and 43.8% insomnia symptoms (95% CI = 35% to 52%). Diagnostic criteria assessments revealed lower prevalence of disorders: 10.3% depression (95% CI = 7% to 13%), 5.6% anxiety (95% CI = 2% to 10%), 9.6% insomnia (95% CI = 1% to 40%), and 1% posttraumatic stress (95% CI = 0% to 84.5%). Suicide pooled incidence was 161.16 per 100 000 individuals per year (95% CI = 82 to 239). Meta-regressions found a statistically significant higher prevalence of anxiety in patients undergoing primary chemoradiation compared with surgery and increased distress in smokers and advanced tumor staging. European samples exhibited lower prevalence of distress. Conclusions Patients with head and neck cancer presented notable prevalence of mental health concerns in all domains. Suicide remains a highly relevant concern. The prevalence of criteria-meeting disorders is significantly lower than clinically relevant symptoms. Investigating the effectiveness of targeted assessments for disorders in highly symptomatic patients is essential. [ABSTRACT FROM AUTHOR]

Objective: Since the update of the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging criteria, there have been few reports on the prognosis of stage III C cervical cancer. Moreover, some studies have drawn controversial conclusions, necessitating further verification. This study aims to evaluate the clinical outcomes and determine the prognostic factors for stage III C cervical cancer patients treated with radical radiotherapy or radiochemotherapy. Methods: The data of 117 stage III C cervical cancer patients (98 III C1 and 19 III C2) who underwent radical radiotherapy or radiochemotherapy were retrospectively analyzed. We evaluated 3-year overall survival (OS) and disease-free survival (DFS) using the Kaplan–Meier method. Prognostic factors were analyzed using the Log-rank test and Cox proportional hazard regression model. The risk of para-aortic lymph node metastasis (LNM) in all patients was assessed through Chi-squared test and logistic regression analysis. Results: For stage III C1 and III C2 patients, the 3-year OS rates were 77.6% and 63.2% (P =.042), and the 3-year DFS rates were 70.4% and 47.4% (P =.003), respectively. The pretreatment location of pelvic LNM, histological type, and FIGO stage was associated with OS (P =.033,.003,.042, respectively); the number of pelvic LNM and FIGO stage were associated with DFS (P =.015,.003, respectively). The histological type was an independent prognostic indicator for OS, and the numbers of pelvic LNM and FIGO stage were independent prognostic indicators for DFS. Furthermore, a pelvic LNM largest short-axis diameter ≥ 1.5 cm and the presence of common iliac LNM were identified as high-risk factors influencing para-aortic LNM in stage III C patients (P =.046,.006, respectively). Conclusions: The results of this study validated the 2018 FIGO staging criteria for stage III C cervical cancer patients undergoing concurrent chemoradiotherapy. These findings may enhance our understanding of the updated staging criteria and contribute to better management of patients in stage III C. [ABSTRACT FROM AUTHOR]

An abnormal glutamate signaling of glioblastoma may contribute to both tumor progression and the generation of glioma-associated epileptic seizures. We hypothesized that the AMPA receptor antagonist perampanel (PER) could attenuate tumor growth and epileptic events. F98 glioma cells, grown orthotopically in Fischer rats, were employed as a model of glioma to investigate the therapeutic efficiency of PER (15 mg/kg) as adjuvant to standard radiochemotherapy (RCT). The epileptiform phenotype was investigated by video-EEG analysis and field potential recordings. Effects on glioma progression were estimated by tumor size quantification, survival analysis and immunohistological staining. Our data revealed that orthotopically-growing F98 glioma promote an epileptiform phenotype in rats. RCT reduced the tumor size and prolonged the survival of the animals. The adjuvant administration of PER had no effect on tumor progression. The tumor-associated epileptic events were abolished by PER application or RCT respectively, to initial baseline levels. Remarkably, PER preserved the glutamatergic network activity on healthy peritumoral tissue in RCT-treated animals. F98 tumors are not only a robust model to investigate glioma progression, but also a viable model to simulate a glioma-associated epileptiform phenotype. Furthermore, our data indicate that PER acts as a potent anticonvulsant and may protect the tumorsurrounding tissue as adjuvant to RCT, but failed to attenuate tumor growth or promote animal survival. [ABSTRACT FROM AUTHOR]

Aim: The optimal management of patients with clinical complete response after neoadjuvant treatment for rectal cancer is controversial. The aim of this study is to compare the morbidity between patients with locally advanced rectal cancer who have had a pathological complete response (pCR) or not after neoadjuvant chemoradiotherapy (NCRT) and total mesorectal excision (TME). The study hypothesis was that pCR may impact the surgical complication rate. Method: A retrospective cohort study was conducted of a prospectively maintained database in Australia and New Zealand, the Binational Colorectal Cancer Audit, that identified patients with locally advanced rectal cancer (<15 cm from anal verge) from 1 January 2007 to 31 December 2019. Patients were included if they had locally advanced rectal cancer and had undergone NCRT and proceeded to surgical resection. Results: There were 4584 patients who satisfied the inclusion criteria, 65% being male. The mean age was 63 years and 11% had a pCR (ypT0N0). TME with anastomosis was performed in 67.8% of patients, and the majority of the cohort received long‐course radiotherapy (81.7%). Both major and minor complications were higher in the TME without anastomosis group (17.3% vs. 14.7% and 30.6% vs. 20.8%, respectively), and the 30‐day mortality was 1.31%. In the TME with anastomosis group, pCR did not contribute to higher rates of surgical complications, but male gender (p < 0.0012), age (p < 0.0001), preoperative N stage (p = 0.0092) and American Society of Anesthesologists (ASA) score ≥3 (p < 0.0002) did. In addition, pCR had no significant effect (p = 0.44) but male gender (p = 0.0047) and interval to surgery (p = 0.015) contributed to higher rates of anastomotic leak. In the TME without anastomosis cohort, the only variable that contributed to higher rates of complications was ASA score ≥3 (p = 0.033). Conclusion: Patients undergoing TME dissection for rectal cancer following NCRT showed no difference in complications whether they had achieved pCR or not. [ABSTRACT FROM AUTHOR]

Objectives: As a few types of glioma, young high-risk low-grade gliomas (HRLGGs) have higher requirements for postoperative quality of life. Although adjuvant chemotherapy with delayed radiotherapy is the first treatment strategy for HRLGGs, not all HRLGGs benefit from it. Accurate assessment of chemosensitivity in HRLGGs is vital for making treatment choices. This study developed a multimodal fusion radiomics (MFR) model to support radiochemotherapy decision-making for HRLGGs. Methods: A MFR model combining macroscopic MRI and microscopic pathological images was proposed. Multiscale features including macroscopic tumor structure and microscopic histological layer and nuclear information were grabbed by unique paradigm, respectively. Then, these features were adaptively incorporated into the MFR model through attention mechanism to predict the chemosensitivity of temozolomide (TMZ) by means of objective response rate and progression free survival (PFS). Results: Macroscopic tumor texture complexity and microscopic nuclear size showed significant statistical differences (p < 0.001) between sensitivity and insensitivity groups. The MFR model achieved stable prediction results, with an area under the curve of 0.950 (95% CI: 0.942–0.958), sensitivity of 0.833 (95% CI: 0.780–0.848), specificity of 0.929 (95% CI: 0.914–0.936), positive predictive value of 0.833 (95% CI: 0.811–0.860), and negative predictive value of 0.929 (95% CI: 0.914–0.934). The predictive efficacy of MFR was significantly higher than that of the reported molecular markers (p < 0.001). MFR was also demonstrated to be a predictor of PFS. Conclusions: A MFR model including radiomics and pathological features predicts accurately the response postoperative TMZ treatment. Clinical relevance statement: Our MFR model could identify young high-risk low-grade glioma patients who can have the most benefit from postoperative upfront temozolomide (TMZ) treatment. Key Points: • Multimodal radiomics is proposed to support the radiochemotherapy of glioma. • Some macro and micro image markers related to tumor chemotherapy sensitivity are revealed. • The proposed model surpasses reported molecular markers, with a promising area under the curve (AUC) of 0.95. [ABSTRACT FROM AUTHOR]

Abstract Background and Aim The German NPC‐GPOH trials introduced treatment including neoadjuvant chemotherapy, radiochemotherapy (RCT) and antiviral treatment in patients aged 25 years or younger with nasopharyngeal cancer (NPC). We conducted a retrospective study on outcomes of patients at the age of ≥26 years treated accordingly at our institution. Methods Consecutive patients who received primary RCT for NPC were included. The Kaplan–Meier method was used to calculate survival probabilities, and the Cox regression analysis was used to test for an influence of the variables on outcomes. Acute and late toxicity were evaluated via CTCAE criteria and LENT/SOMA criteria, respectively. Results In total, 30 patients were included. Diagnosis was made from 09/1994 to 11/2016. The median 5 year overall survival (OS), disease‐free survival (DFS), cancer‐specific survival (CSS) and locoregional recurrence‐free survival (LRC) were 75%, 56%, 83%, and 85%, respectively. We found a negative impact on outcomes (p

BackgroundGlioblastoma (GBM) is a poor prognosis grade 4 glioma. After surgical resection, the standard therapy consists of concurrent radiotherapy (RT) and temozolomide (TMZ) followed by TMZ alone. Our previous data on melanoma patients showed that Dendritic Cell vaccination (DCvax) could increase the amount of intratumoral-activated cytotoxic T lymphocytesMethodsThis is a single-arm, monocentric, phase II trial in two steps according to Simon’s design. The trial aims to evaluate progression-free survival (PFS) at three months and the safety of a DCvax integrated with standard therapy in resected GBM patients. DCvax administration begins after completion of RT-CTwith weekly administrations for 4 weeks, then is alternated monthly with TMZ cycles. The primary endpoints are PFS at three months and safety. One of the secondary objectives is to evaluate the immune response both in vitro and in vivo (DTH skin test).ResultsBy December 2022, the first pre-planned step of the study was concluded with the enrollment, treatment and follow up of 9 evaluable patients. Two patients had progressed within three months after leukapheresis, but none had experienced DCvax-related G3-4 toxicities Five patients experienced a positive DTH test towards KLH and one of these also towards autologous tumor homogenate. The median PFS from leukapheresis was 11.3 months and 12.2 months from surgery.ConclusionsThis combination therapy is well-tolerated, and the two endpoints required for the first step have been achieved. Therefore, the study will proceed to enroll the remaining 19 patients. (Eudract number: 2020-003755-15 https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-003755-15/IT)

An ongoing debate exists regarding the feasibility of placing self-expanding metallic stents (SEMS) within 5 cm of the anal verge. Traditionally, SEMS have been considered contraindicated for patients with a malignant rectal obstruction within this region due to potential impact on the anorectal ring or anal canal, which can cause incontinence, proctalgia, and tenesmus. However, in the case of a 63-year-old female who presented with distention, abdominal pain, and diminishing stool output, the rectal exam identified a bulky fixed mass. Imaging studies revealed large bowel obstruction and high-grade stricture, with a minuscule residual lumen. Endoscopy identified a bulky mass obscuring the lumen at 5 cm from the anal verge, and biopsy confirmed adenocarcinoma. Despite the traditionally held contraindication, a 2.5 cm × 9.0 cm colonic stent was successfully deployed, leading to brisk colonic decompression. This allowed the patient to promptly undergo chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Hypoxia-induced autophagy leads to an increase in vasculogenic-mimicry (VM) and the development of resistance of glioblastoma-cells to bevacizumab (BEV). Chloroquine (HCQ) inhibits autophagy, reduces VM and can thus produce a synergistic effect in anti-angiogenic-therapy by delaying the development of resistance to BEV. We retrospectively compared the combined addition of HCQ+BEV and adjuvant-radiochemotherapy (aRCT) to aRCT alone for recurrent-glioblastoma (rGBM) in regards of overall survival (OS). Between 2006 and 2016, 134 patients underwent neurosurgery for rGBM at our institution. Forty-two patients (Karnofsky-Performance-Score>60%) with primary-glioblastoma underwent repeat-surgery and aRCT for recurrence. Four patients (9.5%) received aRCT+HCQ+BEV. Five patients received aRCT+BEV. In rGBM-patients who were treated with aRCT+HCQ+BEV, median OS was 36.57 months and median post-recurrence-survival (PRS) was 23.92 months while median PRS in the control-group was 9.63 months (p=0.022). In patients who received aRCT+BEV, OS and PRS were 26.83 and 12.97 months, respectively. Although this study was performed on a small number of highly selected patients, it demonstrates a synergistic effect of HCQ+BEV in the treatment of rGBM which previously could be demonstrated based on experimental data. A significant increase of OS in patients who receive aRCT+HCQ+BEV cannot be ruled out and should be further investigated in randomised-controlled-trials. [ABSTRACT FROM AUTHOR]

Background Oral mucositis is a major complication for head and neck cancer (HNC) patients after radiotherapy or chemotherapy. A meta-analysis was performed to assess the efficacy of turmeric in the treatment of oral mucositis in HNC patients. Methods Randomized controlled trials investigating our topic were included in the meta-analysis. The clinical outcomes considered were the severity of oral mucositis, pain level, and weight loss. Results A total of eight articles that met our inclusion criteria were included in our meta-analysis. At the 3-week follow-up visit, the turmeric group showed significantly lower grades of oral mucositis compared to the control group (p = 0.03). When compared to the placebo group, a significant difference in the degree of oral mucositis was observed at the 4-(p = 0.03) and 6-week (p < 0.00001) follow-up visits. No significant difference in pain levels was observed between the turmeric and control groups at any of the follow-up visits. However, a significant improvement in pain levels for the turmeric group when compared with the placebo group was observed only at the 6-week follow-up visit (p = 0.006). Interestingly, a significant improvement in pain levels was observed for the turmeric group at the 2-, 4-, 5-, and 6-week follow-up visits (p < 0.05) when compared to the non-placebo group. The turmeric group showed less weight loss than the control group at the final follow-up visit (p = 0.03). Conclusion Our meta-analysis showed that using turmeric may be effective in improving both the severity of oral mucositis and pain levels in HNC patients who have received radiotherapy or radiochemotherapy. In addition, the turmeric group experienced less weight loss. [ABSTRACT FROM AUTHOR]

Aim: Local excision (LE) in selected cases after neoadjuvant radiochemotherapy (RCT) for locally advanced rectal cancer in clinically complete or major responders has been recently reported as an alternative to standard radical resection. Completion total mesorectal excision (cTME) is generally performed when high‐risk pathological features are found in LE surgical specimens. The aim of this study was to evaluate the incidence of residual tumour and lymph node metastases after cTME in patients previously treated by RCT + LE. The secondary aims were to quantify the rate of postoperative morbidity and mortality and to evaluate the long‐term oncological outcome of this group of patients. Methods: All patients treated from 2007 to 2020 by LE for locally advanced rectal cancer with a clinically complete or major response to RCT who had a subsequent cTME for high‐risk pathological factors (ypT >1 and/or TRG >2 and/or positive margins) were included in this multicentre retrospective study. Pathological data, postoperative short‐term morbidity (classified according to Clavien–Dindo) and mortality and oncological long‐term outcome after cTME were recorded in a database. Statistical analysis was performed using Wizard for iOS version 1.9.31. Results: A total of 47 patients were included in the study. The rate of R0 resection was 95.7%, and a sphincter‐saving procedure was performed in 37 patients (78.7%), with a protective stoma rate of 78.4%. In 28 cases (59.6%), it was possible to perform a minimally invasive approach. A residual tumour (pT and/or pN) on cTME specimens was found in 21 cases (44.7%). The rate of lymph node metastases was 12.8%. The overall short‐term (within 30 days) postoperative morbidity was 34%, but grade >2 postoperative complications occurred in only nine patients (19.1%), with a reoperation rate of 6.4%. No short‐term postoperative deaths occurred. At a median follow‐up of 57 months (range: 21–174), the long‐term stoma‐free rate was 70.2%, and the actuarial 5‐year overall survival (OS), disease‐free survival (DFS) and local control (LC) were 86.7%, 88.9% and 95.7%, respectively. Conclusion: When patients exhibit high‐risk pathological factors after RCT + LE, cTME should be suggested due to the high risk of residual tumour or lymph node involvement (44.7%). The results after cTME in terms of the rate of R0 resection, sphincter‐saving procedure, postoperative morbidity and mortality and long‐term oncological outcome seem to be acceptable and do not represent a contraindication to use LE as a first‐step treatment in patients with major or complete clinical response after RCT. [ABSTRACT FROM AUTHOR]

Ganglioneuromas (GN) are benign neuroblastic tumors that arise from neural crest cells. Since they present with nonspecific symptoms, diagnosis is often incidental. We are reporting a case of an adult appendiceal GN incidentally found during rectal cancer surgery. A 42-year-old male was diagnosed with recurrent rectal cancer after experiencing urinary difficulties and buttock pain. A multiple-stage pelvic exenteration was carried out after neoadjuvant chemotherapy and chemoradiation. Prophylactic appendectomy was done during the course of surgery, and pathology reported an appendix with GN at the distal tip. GN are often found incidentally and rarely cause appendicitis. Depending on their location and size, they might become symptomatic. While there is some controversy on whether surgery is the treatment of choice for all GN, diagnosis is rarely apparent preoperatively, and all appendiceal masses should be resected. [ABSTRACT FROM AUTHOR]

IntroductionAnal squamous cell carcinoma (ASC) is a rare gastrointestinal malignancy showing an increased incidence over the past decades. YKL-40 is an immune modulator and pro-angiogenetic factor that showed a promising prognostic and predictive potential in several malignancies, but limited data are available for ASC. This study aims to provide an extensive evaluation of the prognostic and predictive role of YKL-40 in a multicenter cohort of ASC patients.MethodsWe retrospectively retrieved 72 consecutive cases of ASC diagnosed between February 2011 and March 2021. Both serum and tissue protein expression of YKL-40 were assessed, the latter in ASC tumor cells and peritumor immune cells.ResultsIncreased YKL-40 serum levels at the time of diagnosis were associated with older age (p = 0.035), presence of cardiovascular/metabolic comorbidities (p = 0.007), and death for any cause (p = 0.011). In addition, high serum levels of YKL-40 were associated with a poor prognosis (HR: 2.82, 95% CI: 1.01–7.84; p = 0.047). Protein expression of YKL-40 in ASC tumor cells was significantly associated with low tumor grade (p = 0.031), while the increased expression in peritumor immune cells was associated with a worse response of patients to chemoradiotherapy (p = 0.007). However, YKL-40 protein expression in ASC tumor cells or peritumor immune cells did not significantly impact patient overall survival.DiscussionIn conclusion, YKL-40 resulted a relevant prognostic (serum level) and predictive (tissue protein expression in peritumor immune cells) biomarker and can considerably improve ASC patient clinical management.

Background and purpose: To assess feasibility, toxicity and outcome of moderately hypofractionated radiotherapy concomitant to capecitabine after induction chemotherapy for advanced pancreatic cancer. Materials and methods: Patients with advanced pancreatic cancer without distant progression after induction chemotherapy (CHT) were considered. Radiochemotherapy (RCT) consisted of 44.25 Gy in 15 fractions to the tumor and involved lymph-nodes concomitant to capecitabine 1250 mg/m2/day. Feasibility and toxicity were evaluated in all pts. Overall survival (OS), progression free survival (PFS), distant PFS (DPFS) and local PFS (LPFS) were assessed only in stage III patients. Results: 254 patients, 220 stage III, 34 stage IV, were treated. Median follow up was 19 months. Induction CHT consisted of Gemcitabine (35 patients), or drug combination (219 patients); median duration was 6 months.Four patients (1.6 %) did not complete RT (1 early progression, 3 toxicity), median duration of RT was 20 days, 209 patients (82 %) received ≥ 75 % of capecitabine dose.During RCT G3 gastrointestinal toxicity occurred in 3.2% of patients, G3-G4 hematologic toxicity in 5.4% of patients. Subsequently, G3, G4, G5 gastric or duodenal lesions occurred in 10 (4%), 2 (0.8%) and 1 patients (0.4%), respectively.Median PFS, LPFS, and DPFS were 11.9 months (95 % CI:11.4–13), 16 months (95 % CI:14.2–17.3) and 14.0 months (95 % CI:12.6–146.5), respectively.Median OS was 19.5 months (95 % CL:18.1–21.3). One- and two-year survival were 85.2 % and 36 %, respectively. Conclusions: The present schedule of hypofractionated RT after induction CHT is feasible with acceptable toxicity rate and provides an outcome comparable with that achievable with standard doses and fractionation.

Background/Objectives: The objective of this study was to assess the connection between the systemic inflammation response index (SIRI) values and failure patterns of patients with IDH wild-type glioblastoma (GB) who underwent radiotherapy (RT) with FLAIR-based gross tumor volume (GTV) delineation. Methods: Seventy-one patients who received RT at a dose of 60 Gy to the GTV and 50 Gy to the clinical target volume (CTV) and had documented recurrence were retrospectively analyzed. Each patient’s maximum distance of recurrence (MDR) from the GTV was documented in whichever plane it extended the farthest. The failure patterns were described as intra-GTV, in-CTV/out-GTV, distant, and intra-GTV and distant. For analytical purposes, the failure pattern was categorized into two groups, namely Group 1, intra-GTV or in-CTV/out-GTV, and Group 2, distant or intra-GTV and distant. The SIRI was calculated before surgery and corticosteroid administration. A receiver operating characteristic (ROC) curve analysis was used to determine the optimal SIRI cut-off that distinguishes between the different failure patterns. Results: Failure occurred as follows: intra-GTV in 40 (56.3%), in-CTV/out-GTV in 4 (5.6%), distant in 18 (25.4%), and intra-GTV + distant in 9 (12.7%) patients. The mean MDR was 13.5 mm, and recurrent lesions extended beyond 15 mm in only seven patients. Patients with an SIRI score ≥ 3 demonstrated a significantly higher incidence of Group 1 failure patterns than their counterparts with an SIRI score < 3 (74.3% vs. 50.0%; p = 0.035). Conclusions: The present results show that using the SIRI with a cut-off value of ≥3 significantly predicts failure patterns. Additionally, the margin for the GTV can be safely reduced to 15 mm when using FLAIR-based target delineation in patients with GB.

Simple Summary: Neoadjuvant radiochemotherapy (RCT) and total neoadjuvant therapy (TNT) have significantly reduced local recurrence rates in rectal cancer. However, late local recurrences remain a distinct issue. Most recurrences occur within two years; general follow-up programs typically last for 5 years. We found four patients with late local recurrences > 8 years after surgery. This study highlights that neoadjuvant therapy delays local recurrence. Neoadjuvant radiochemotherapy (RCT) and lately total neoadjuvant therapy (TNT) improved local recurrence rates of rectal cancer significantly compared to total mesorectal excision (TME) alone. Yet the occurrence and impact of late local recurrences after many years appears to be a distinct biological problem. We included n = 188 patients with rectal cancer after RCT and radical resection in this study; n = 38 of which had recurrent disease (sites: local (8.0%), liver (6.4%), lung (3.7%)). We found that 68% of all recurrences developed within the first two years. Four patients, however, experience recurrence >8 years after surgery. Here, we report and characterize four cases of late local recurrence (10% of patients with recurrent disease), suggesting that neoadjuvant therapy in principle delays local recurrence. [ABSTRACT FROM AUTHOR]

Simple Summary: Identification of the optimal treatment strategy is challenging in elderly with non-small cell lung cancer (NSCLC). Outcomes (1) in elderly vs. younger patients and (2) with low-dose cisplatin vs. cisplatin/vinorelbine were studied. Elderly included more males, had a lower Karnofsky index, more comorbidities, and lower stages. Low-dose cisplatin patients had higher age, more comorbidities, and lower stages. We observed reduced dermatitis and dysphagia and increased anemia and thrombocytopenia in elderly, without increased ≥grade 3 toxicities. Low-dose cisplatin was less toxic than cisplatin/vinorelbine. Survival was lower in elderly vs. younger and comparable between both chemotherapy protocols. In elderly, gender, Karnofsky index, stage, and multimodal treatment (including additional surgery/systemic therapy) were prognostic factors. In elderly, we found acceptable toxicities with radiotherapy but the need for the improvement of outcomes. Multimodal strategies showed a favorable prognosis and can reasonably be considered. Low-dose cisplatin should be discussed on an individual basis due to favorable toxicity and outcomes. Identification of the optimal treatment strategy is challenging in elderly with localized non-small cell lung cancer (NSCLC). Concurrent chemotherapy with low-dose cisplatin represents an option for elderly. Outcomes (1) in elderly (≥70 years, n = 158) vs. younger patients (n = 188) and (2), independently of age, in definitive radiochemotherapy, with low-dose cisplatin (n = 125) vs. cisplatin/vinorelbine (n = 76) were studied. Elderly included more males, had a lower Karnofsky index, more comorbidities, and lower stages. Low-dose cisplatin patients (vs. cisplatin/vinorelbine) had higher age, more comorbidities, and lower stages. We observed reduced dermatitis and dysphagia and increased anemia and thrombocytopenia in elderly vs. younger patients, without increased ≥grade 3 toxicities. Low-dose cisplatin was less toxic than cisplatin/vinorelbine. Survival outcomes were lower in elderly vs. younger and comparable between low-dose cisplatin and cisplatin/vinorelbine. In elderly, gender, Karnofsky index, stage, and multimodal treatment (including additional surgery/systemic therapy) were identified as prognostic factors. In conclusion, we found evidence for an acceptable toxicity profile and the need for improvement of outcomes in elderly with localized NSCLC. Multimodal strategies (including additional surgery/systemic treatment) showed favorable outcomes and should be reasonably considered in elderly who are deemed fit enough. Low-dose cisplatin should be discussed on an individual basis due to favorable toxicity and outcomes. [ABSTRACT FROM AUTHOR]

Background: To retrospectively access outcome, adverse events and prognostic factors in oropharyngeal carcinoma (OPC) patients treated with intensity-modulated radiotherapy (IMRT). Methods: Ninety-eight OPC patients were treated between 2000 and 2015. Thirty-three patients received definitive and 65 adjuvant radiotherapy. Seventy-one percent had simultaneous chemotherapy. Patients were systematically followed up (mean 114 months, range 19-197 months). Statistical analysis used Kaplan-Meier method, Cox regression analysis, and log-rank test. Adverse events were classified according to common toxicity criteria version (CTCAE) 4.03. Results: The 1-, 5-, and 10-year overall survival rates in the adjuvant vs. definitive cohort were 90.8% vs. 66.7%, 67.4% vs. 33.1%, and 57.7% vs. 16.5%. Survival in the adjuvant cohort was significantly longer than in the definitive cohort (P < 0.00005). Patients <65 years had a significantly longer survival than older patients. Locoregional tumor control rates after 1-, 5-, and 10 years in the adjuvant vs. definitive cohort were 90.2% vs. 66.7%, 82.2% vs 45.4%, and 72.1% vs. 30.3%. Locoregional tumor control in the adjuvant cohort was significantly longer than in the definite cohort (P < 0.005). Distant metastases were diagnosed in 20.4% of all patients. Most patients had mild CTCAE grade 1 and 2 adverse events and mild late adverse events including xerostomia, dysphagia, and lymphedema. Conclusion: Intensity-modulated radiotherapy for OPC is an important part of the treatment algorithm alone and in particular after surgery while the additional benefits of chemotherapy might be age dependent. Despite advanced tumor stages, nearly half of our patients were alive in the long term. The majority of patients had relatively mild chronic adverse events. [ABSTRACT FROM AUTHOR]

Simple Summary: Neoadjuvant chemotherapy is the standard treatment for locally advanced rectal cancer. Preoperative chemoradiotherapy yields clinically significant tumor regression; while some patients exhibit a minimal response, others exhibit a complete pathologic response. We developed deep learning and machine learning models to predict chemoradiotherapy response across external tests using multicenter data. The machine learning model, which used harmonized image features extracted from 18F-FDG PET, showed higher performance and demonstrated reproducibility through external tests compared to the deep learning models using 18F-FDG PET images. Our study highlights the feasibility of predicting the chemoradiotherapy response of individual patients using non-invasive and reliable image feature values. We developed machine and deep learning models to predict chemoradiotherapy in rectal cancer using 18F-FDG PET images and harmonized image features extracted from 18F-FDG PET/CT images. Patients diagnosed with pathologic T-stage III rectal cancer with a tumor size > 2 cm were treated with neoadjuvant chemoradiotherapy. Patients with rectal cancer were divided into an internal dataset (n = 116) and an external dataset obtained from a separate institution (n = 40), which were used in the model. AUC was calculated to select image features associated with radiochemotherapy response. In the external test, the machine-learning signature extracted from 18F-FDG PET image features achieved the highest accuracy and AUC value of 0.875 and 0.896. The harmonized first-order radiomics model had a higher efficiency with accuracy and an AUC of 0.771 than the second-order model in the external test. The deep learning model using the balanced dataset showed an accuracy of 0.867 in the internal test but an accuracy of 0.557 in the external test. Deep-learning models using 18F-FDG PET images must be harmonized to demonstrate reproducibility with external data. Harmonized 18F-FDG PET image features as an element of machine learning could help predict chemoradiotherapy responses in external tests with reproducibility. [ABSTRACT FROM AUTHOR]

Background: Tumor hypoxia is associated with resistance to radiotherapy and chemotherapy. In head and neck squamous cell carcinoma (HNSCC), nimorazole, an oxygen mimic, combined with radiotherapy (RT) enabled to improve loco-regional control (LRC) in some patients with hypoxic tumors but it is unknown whether this holds also for radiochemotherapy (RCTx). Here, we investigated the impact of nimorazole combined with RCTx in HNSCC xenografts and explored molecular biomarkers for its targeted use. Methods: Irradiations were performed with 30 fractions in 6 weeks combined with weekly cisplatin. Nimorazole was applied before each fraction, beginning with the first or after ten fractions. Effect of RCTx with or without addition of nimorazole was quantified as permanent local control after irradiation. For histological evaluation and targeted gene expression analysis, tumors were excised untreated or after ten fractions. Using quantitative image analysis, micromilieu parameters were determined. Results: Nimorazole combined with RCTx significantly improved permanent local control in two tumor models, and showed a potential improvement in two additional models. In these four models, pimonidazole hypoxic volume (pHV) was significantly reduced after ten fractions of RCTx alone. Our results suggest that nimorazole combined with RCTx might improve TCR compared to RCTx alone if hypoxia is decreased during the course of RCTx but further experiments are warranted to verify this association. Differential gene expression analysis revealed 12 genes as potential for RCTx response. When evaluated in patients with HNSCC who were treated with primary RCTx, these genes were predictive for LRC. Conclusions: Nimorazole combined with RCTx improved local tumor control in some but not in all HNSCC xenografts. We identified prognostic biomarkers with the potential for translation to patients with HNSCC. [ABSTRACT FROM AUTHOR]

Purpose: In 2012, the CROSS trial implemented a new neoadjuvant radiochemotherapy protocol for patients with locally advanced, resectable cancer of the esophagus prior to scheduled surgery. There are only limited studies comparing the CROSS protocol with a PF-based (cisplatin/5-fluorouracil) nRCT protocol. Methods: In this retrospective, monocentric analysis, 134 patients suffering from esophageal cancer were included. Those patients received either PF-based nRCT (PF group) or nRCT according to the CROSS protocol (CROSS group) prior to elective en bloc esophagectomy. Perioperative mortality and morbidity, nRCT-related toxicity, and complete pathological regression were compared between both groups. Logistic regression analysis was performed in order to identify independent factors for pathological complete response (pCR). Results: Thirty-day/hospital mortality showed no significant differences between both groups. Postoperative complications ≥ grade 3 according to Clavien-Dindo classification were experienced in 58.8% (PF group) and 47.6% (CROSS group) (p = 0.2) respectively. nRCT-associated toxicity ≥ grade 3 was 30.8% (PF group) and 37.2% (CROSS group) (p = 0.6). There was no significant difference regarding the pCR rate between both groups (23.5% vs. 30.5%; p = 0.6). In multivariate analysis, SCC (OR 7.7; p < 0.01) and an initial grading of G1/G2 (OR 2.8; p = 0.03) were shown to be independent risk factors for higher rates of pCR. Conclusion: We conclude that both nRCT protocols are effective and safe. There were no significant differences regarding toxicity, pathological tumor response, and postoperative morbidity and mortality between both groups. Squamous cell carcinoma (SCC) and favorable preoperative tumor grading (G1 and G2) are independent predictors for higher pCR rate in multivariate analysis. [ABSTRACT FROM AUTHOR]

Abstract Background Tumor hypoxia is associated with resistance to radiotherapy and chemotherapy. In head and neck squamous cell carcinoma (HNSCC), nimorazole, an oxygen mimic, combined with radiotherapy (RT) enabled to improve loco-regional control (LRC) in some patients with hypoxic tumors but it is unknown whether this holds also for radiochemotherapy (RCTx). Here, we investigated the impact of nimorazole combined with RCTx in HNSCC xenografts and explored molecular biomarkers for its targeted use. Methods Irradiations were performed with 30 fractions in 6 weeks combined with weekly cisplatin. Nimorazole was applied before each fraction, beginning with the first or after ten fractions. Effect of RCTx with or without addition of nimorazole was quantified as permanent local control after irradiation. For histological evaluation and targeted gene expression analysis, tumors were excised untreated or after ten fractions. Using quantitative image analysis, micromilieu parameters were determined. Results Nimorazole combined with RCTx significantly improved permanent local control in two tumor models, and showed a potential improvement in two additional models. In these four models, pimonidazole hypoxic volume (pHV) was significantly reduced after ten fractions of RCTx alone. Our results suggest that nimorazole combined with RCTx might improve TCR compared to RCTx alone if hypoxia is decreased during the course of RCTx but further experiments are warranted to verify this association. Differential gene expression analysis revealed 12 genes as potential for RCTx response. When evaluated in patients with HNSCC who were treated with primary RCTx, these genes were predictive for LRC. Conclusions Nimorazole combined with RCTx improved local tumor control in some but not in all HNSCC xenografts. We identified prognostic biomarkers with the potential for translation to patients with HNSCC.

Background: Intensity-modulated conformal radiotherapy (IMRT) has become the technique of choice for the treatment of locally advanced or inoperable nonsmall cell lung cancer (NSCLC). Nevertheless, this technique presents dosimetric uncertainties, particularly in treating moving targets such as pulmonary neoplasms. Moreover, it theoretically increases the risk of isolated nodal failure (INF) due to reduced incidental irradiation. Objective: The objective of this study was to evaluate the efficacy and safety of IMRT in patients with inoperable NSCLC and to describe the pattern of relapses. Methods: Patients with locally advanced NSCLC treated with radiotherapy and chemotherapy between 2015 and 2018 at the Oscar Lambret Center were retrospectively included in the study. Overall and progression-free survival were estimated using the Kaplan–Meier method. The cumulative incidence of the different components of relapse was estimated using the Kalbfleisch and Prentice method. Prognostic factors for relapse/death were investigated using the Cox model. A comparison with literature data was performed using a onesample log-rank test. Results: Seventy patients were included, and 65 patients (93%) had stage III disease. All the patients received chemotherapy, most frequently with cisplatin and navelbine. The dose received was 66 Gy administered in 33 fractions. The median follow-up and survival were 49.1 and 39.1 months, respectively. A total of 35 deaths and 43 relapses, including 29 with metastatic components, were reported. The overall survival rates at 1 and 2 years were 80.2% (95% confidence interval 68.3%-88.0%) and 67.2% (95% confidence interval 54.2%-77.3%), respectively. Locoregional relapse was observed in 14 patients, including two INF, one of which was located in the lymph node area adjacent to the clinical target volume. Median relapse-free survival was 15.2 months. No variable was statistically associated with the risk of relapse/death in multivariate analysis. Seven patients (10%) experienced grade 3 or higher toxicity. Conclusion: The use of IMRT for locally advanced or inoperable NSCLC led to favorable long-term clinical outcomes. The rate of locoregional relapse, particularly isolated lymph node failure, was low and comparable with that of the three-dimensional radiotherapy series, as was the rate of early and late toxicities. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiochemotherapy (RCT) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) causes side effects in healthy tissue such as the sternocleidomastoid muscle (SCM). These side effects depend on the interval between completion of RCT and restaging CT. For salvage surgery, the optimal time window for surgery is clinically postulated at between 6 and 12 weeks after completion of RCT. Thus, no extensive tissue fibrosis is to be expected. This interval is based on clinical studies exploring surgical complications. Studies directly exploring radiation-induced changes of the SCM in HNSCC patients are sparse. This study applied radiomics to quantify radiation-induced changes in the SCM and paravertebral musculature (PVM). In 98 locally advanced HNSCC patients, three radiomic key features (volume, mean positivity of pixels, uniformity) were analyzed in CT scans before and in the mean 8 weeks after treatment. No significant changes in radiomic key features were observed after adjustment for changes in body mass index (BMI). These data support the clinically postulated time window for salvage surgery of 6 to 12 weeks. Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) frequently require primary radiochemotherapy (RCT). Despite intensity modulation, the desired radiation-induced effects observed in HNSCC may also be observed as side effects in healthy tissue, e.g., the sternocleidomastoid muscle (SCM). These side effects (e.g., tissue fibrosis) depend on the interval between the completion of RCT and restaging CT. For salvage surgery, the optimal time window for surgery is currently clinically postulated at between 6 and 12 weeks after completion of RCT. Thus, no extensive tissue fibrosis is to be expected. This interval is based on clinical studies exploring surgical complications. Studies directly exploring radiation-induced changes of the SCM in HNSCC patients are sparse. The present study quantified tissue alterations in the SCM and paravertebral musculature (PVM) after RCT, applying radiomics to determine the optimal time window for salvage surgery. Three radiomic key parameters, (1) volume, (2) mean positivity of pixels (MPP), and (3) uniformity, were extracted with mint LesionTM in the staging CTs and restaging CTs of 98 HNSCC patients. Of these, 25 were female, the mean age was 62 (±9.6) years, and 80.9% were UICC Stage IV. The mean restaging interval was 55 (±28; range 29–229) days. Only the mean volume significantly decreased after RCT, from 9.0 to 8.4 and 96.5 to 91.9 mL for the SCM and PVM, respectively (both p = 0.007, both Cohen's d = 0.28). In addition, the mean body mass index (BMI) decreased from 23.9 (±4.2) to 21.0 (±3.6) kg/m² (p < 0.001; Cohen's d = 0.9). The mean BMI decreased significantly and was correlated with the volume decrease for the SCM (r = 0.27; p = 0.007) and PVM (r = 0.41; p < 0.001). If t-test p-values were adjusted for the BMI decrease, no significant change in volumes for the SCM and PVM was observed (both p > 0.05). The present data support the clinically postulated optimal interval for salvage surgery of 6 to 12 weeks. [ABSTRACT FROM AUTHOR]

Locally advanced rectal cancer has a high risk of local recurrence which can be reduced by multimodal therapy. Neoadjuvant radiotherapy or radiochemotherapy has been established. Nevertheless, this has not proved to improve overall survival. The benefit of adjuvant chemotherapy after neoadjuvant radiotherapy or radiochemotherapy remains unclear. Current studies are investigating total neoadjuvant therapy with different sequences of radiotherapy and chemotherapy followed by rectal resection. This procedure shows high pathologic complete remissions up to 28 % as well as an improvement in disease-free and metastasis-free survival. Under study conditions, in case of clinical complete remission, watchful waiting with close follow-up and surgery can be considered only in case of local tumor recurrence. [ABSTRACT FROM AUTHOR]

Purpose: We analyzed clinical features and the representative HE-stained pathologic images to predict 5-year overall survival via the deep-learning approach in cervical cancer patients in order to assist oncologists in designing the optimal treatment strategies. Methods: The research retrospectively collected 238 non-surgical cervical cancer patients treated with radiochemotherapy from 2014 to 2017. These patients were randomly divided into the training set (n = 165) and test set (n = 73). Then, we extract deep features after segmenting the HE-stained image into patches of size 224 × 224. A Lasso–Cox model was constructed with clinical data to predict 5-year OS. C-index evaluated this model performance with 95% CI, calibration curve, and ROC. Results: Based on multivariate analysis, 2 of 11 clinical characteristics (C-index 0.68) and 2 of 2048 pathomic features (C-index 0.74) and clinical–pathomic model (C-index 0.83) of nomograms predict 5-year survival in the training set, respectively. In test set, compared with the pathomic and clinical characteristics used alone, the clinical–pathomic model had an AUC of 0.750 (95% CI 0.540–0.959), the clinical predictor model had an AUC of 0.729 (95% CI 0.551–0.909), and the pathomic model AUC was 0.703 (95% CI 0.487–0.919). Based on appropriate nomogram scores, we divided patients into high-risk and low-risk groups, and Kaplan–Meier survival probability curves for both groups showed statistical differences. Conclusion: We built a clinical–pathomic model to predict 5-year OS in non-surgical cervical cancer patients, which may be a promising method to improve the precision of personalized therapy. [ABSTRACT FROM AUTHOR]

Abstract Background Hypoxia-mediated radioresistance is the main obstacle to the successful treatment of glioblastoma (GBM). Enhancing hypoxic radiosensitivity and alleviating tumor hypoxia are both effective means to improve therapeutic efficacy, and the combination of the two is highly desirable and meaningful. Results Herein, we construct a low-dose pleiotropic radiosensitive nanoformulation consisting of a high-Z atomic nanocrystal core and mesoporous silica shell, surface-modified with angiopep-2 (ANG) peptide and loaded with nitric oxide (NO) donor and hypoxia-activated prodrug (AQ4N). Benefiting from ANG-mediated transcytosis, this nanoformulation can efficiently cross the BBB and accumulate preferentially in the brain. Low-dose radiation triggers this nanoformulation to exert a three-pronged synergistic therapeutic effect through high-Z-atom-dependent dose deposition enhancement, NO-mediated hypoxia relief, and AQ4N-induced hypoxia-selective killing, thereby significantly inhibiting GBM in situ growth while prolonging survival and maintaining stable body weight in the glioma-bearing mice. Meanwhile, the proposed in vivo 9.4 T BOLD/DWI can realize real-time dynamic assessment of local oxygen supply and radiosensitivity to monitor the therapeutic response of GBM. Conclusions This work provides a promising alternative for hypoxia-specific GBM-targeted comprehensive therapy, noninvasive monitoring, and precise prognosis. Graphical Abstract

BackgroundIntensity-modulated conformal radiotherapy (IMRT) has become the technique of choice for the treatment of locally advanced or inoperable non-small cell lung cancer (NSCLC). Nevertheless, this technique presents dosimetric uncertainties, particularly in treating moving targets such as pulmonary neoplasms. Moreover, it theoretically increases the risk of isolated nodal failure (INF) due to reduced incidental irradiation.ObjectiveThe objective of this study was to evaluate the efficacy and safety of IMRT in patients with inoperable NSCLC and to describe the pattern of relapses.MethodsPatients with locally advanced NSCLC treated with radiotherapy and chemotherapy between 2015 and 2018 at the Oscar Lambret Center were retrospectively included in the study. Overall and progression-free survival were estimated using the Kaplan–Meier method. The cumulative incidence of the different components of relapse was estimated using the Kalbfleisch and Prentice method. Prognostic factors for relapse/death were investigated using the Cox model. A comparison with literature data was performed using a one-sample log-rank test.ResultsSeventy patients were included, and 65 patients (93%) had stage III disease. All the patients received chemotherapy, most frequently with cisplatin and navelbine. The dose received was 66 Gy administered in 33 fractions. The median follow-up and survival were 49.1 and 39.1 months, respectively. A total of 35 deaths and 43 relapses, including 29 with metastatic components, were reported. The overall survival rates at 1 and 2 years were 80.2% (95% confidence interval 68.3%-88.0%) and 67.2% (95% confidence interval 54.2%-77.3%), respectively. Locoregional relapse was observed in 14 patients, including two INF, one of which was located in the lymph node area adjacent to the clinical target volume. Median relapse-free survival was 15.2 months. No variable was statistically associated with the risk of relapse/death in multivariate analysis. Seven patients (10%) experienced grade 3 or higher toxicity.ConclusionThe use of IMRT for locally advanced or inoperable NSCLC led to favorable long-term clinical outcomes. The rate of locoregional relapse, particularly isolated lymph node failure, was low and comparable with that of the three-dimensional radiotherapy series, as was the rate of early and late toxicities.

Colorectal cancer remains one of the most commonly diagnosed cancers. Advanced rectal cancer patients receive neoadjuvant radiochemotherapy as well as surgery and suffer from reduced health-related quality of life due to various side effects. We were interested in the role of the COVID-19 pandemic and how it affected those patients' quality of life. A total of 489 advanced rectal cancer patients from the University Hospital Erlangen in Germany were surveyed between May 2010 and March 2022 and asked to fill out the EORTC QLQ-C30 and QLQ-CR38 questionnaires over eight different time points: at the beginning, during and after radiochemotherapy, right before surgery, and in yearly intervals after surgery for up to four years. Answers were converted to scores to compare the COVID-19 period to the time before March 2020, focusing on the follow-ups, the developments over time—including by sex and age—and the influence of the TNM cT-stage. Overall, a trend of impaired functional and symptom scores was found across all surveys with few significances (body image −10.6 percentage points (pp) after one year; defecation problems +13.5 pp, insomnia +10.2 pp and weight loss +9.8 pp after three years; defecation problems +11.3 pp after four years). cT4-stage patients lost significantly more weight than their cT1-3-stage counterparts (+10.7 to 13.7 pp). Further studies should be conducted to find possible causes and develop countermeasures for future major infectious diseases. [ABSTRACT FROM AUTHOR]

Objective: Mean lung dose (MLD) and percent of total lung (TL) volume that receive a dose greater than 20 Gy (V20) have been the most validated parameters in the prediction of radiation pneumonitis (RP). However, these parameters present mean values of TL parenchyma and predict the right and the left lung as a unique functional organ unit, not take into account the difference in function and dose density between the lungs. Furthermore, there have been very limited data evaluating ipsilateral lung dosimetric constraints in addition to TL parameters to predict RP in non-small cell lung cancer (NSCLC) patients treated with radiochemotherapy (RCT). Methods: Between 2010 and 2017, clinical-radiological findings of NSCLC patients treated with RCT were evaluated in terms of RP, retrospectively. MLD, V20, and V30 values of ipsilateral lung were assessed from dose-volume histogram and registered. The primary endpoint was to assess the relation between ipsilateral lung dose constraints and RP risk. Results: There were 75 patients. There was =Grade 2 RP in 33 cases (%44). In univariate analysis, ipsilateral MLD, ipsilateral V20, ipsilateral V30, and TL V30 were found to be significant. Ipsilateral MLD and PTV were found to be the independent risk factors for RP. Cutoff values for RP risk were determined as 18Gy, 35%, and 28% for ipsilateral MLD, ipsilateral V20, and ipsilateral V30, respectively. Predictive values for ipsilateral MLD and ipsilateral V20 were higher than TL. Conclusions: In NSCLC patients treated with RCT, MLD, V20, and V30 values of ipsilateral lung parameters might increase the predictability of RP risk in addition to TL parameters. Advances in Knowledge: Cutoff values for RP risk were determined as 18Gy, 35%, and 28% for ipsilateral MLD, ipsilateral V20, and ipsilateral V30, respectively. Predictive values for ipsilateral MLD and ipsilateral V20 were higher than TL. [ABSTRACT FROM AUTHOR]

Simple Summary: The prognosis of pancreatic cancer is always serious. In most cases, the cancer is diagnosed at an advanced stage. The treatment is based on the combination of many treatment methods. In the presented work, we focus on the analysis of the role of radiotherapy in the radical treatment of pancreatic cancer. Radiotherapy in combination with chemotherapy or as stereotactic radiotherapy after chemotherapy contributes to the improvement of the results of preoperative treatment in pancreatic cancers with borderline resectability. In locally advanced cases, the use of radiotherapy increases the probability of local cure and reduces the intensity of pain. Therefore, the use of radiotherapy in subsequent stages of treatment in patients with locally advanced pancreatic cancer should be considered. The diagnosis rate of pancreatic cancer is steadily increasing. The average age of onset is close to 70 years. In most cases, the disease is diagnosed at an advanced stage. The indications for and techniques of radiotherapy are changing over time. The aim of this thesis is to present the role and possibilities of radiotherapy from the perspective of radiation oncologist. The most common cause of treatment failure in pancreatic cancer remains generalisation. The implementation of new systemic treatment regimens contributes to improved treatment outcomes regardless of the stage of the disease. With improved treatment outcomes in terms of the incidence of distant metastases, the impact of local curability on the length and quality of life of patients increases. Modern radiotherapy offers the opportunity to achieve high local cure rates. Postoperative radiotherapy in combination with chemotherapy seems justified in the group of postoperative pancreatic cancer patients with pT3 and pN+ features. In the group of patients with borderline resectable pancreatic cancer, the impact of radiotherapy in combination with the latest chemotherapy regimens is difficult to define clearly. In the setting of a diagnosis of advanced pancreatic cancer, radiotherapy, especially stereotactic radiotherapy, in combination with chemotherapy, contributes to improved local curability and allows to achieve a significantly reduced level of pain. [ABSTRACT FROM AUTHOR]

Objective: Epilepsy is a common comorbidity of glioblastoma. Seizures may occur in various phases of the disease. We aimed to assess potential risk factors for seizures in accordance with the point in time at which they occurred. Methods: We retrospectively analyzed medical files of adult patients with de novo glioblastoma treated at our institution between January 2006 and January 2020. We categorized seizures as preoperative seizures (POS), early postoperative seizures (EPS; before initiation of radio[chemo]therapy [RCT]), seizures during radiotherapy (SDR; during or <30 days after RCT), and posttherapeutic seizures (PTS; ≥30 days after completion of RCT). We addressed associations between patients' characteristics and their seizures. Results: In the final cohort (N = 520), 292 patients experienced seizures. POS, EPS, SDR, and/or PTS occurred in 29.6% (154/520), 6.0% (31/520), 13.8% (70/509), and 36.1% (152/421) of patients, respectively. POS occurred more frequently in patients with higher Karnofsky Performance Scale scores (odds ratio [OR] = 3.27, p =.001) and tumor location in the temporal lobe (OR = 1.51, p =.034). None of the parameters we analyzed was related to the occurrence of EPS. SDR were independently associated with tumor location (parietal lobe, OR = 1.86, p =.027) and POS, but not EPS, and were independent of RCT. PTS were independently associated with tumor progression (OR = 2.32, p <.001) and with occurrence of SDR (OR = 3.36, p <.001), and negatively correlated with temporal lobe location (OR =.58, p <.014). In patients with tumors exclusively located in the temporal lobe, complete tumor resection was associated with a decreased risk of postoperative seizures. Significance: Seizures in glioblastoma patients have various, time‐dependent risk factors. Temporal lobe localization was a risk factor for preoperative seizures; surgery may have had a protective effect in these patients. RCT did not have dose‐dependent pro‐ or anticonvulsive effects. PTS were associated with tumor progression. [ABSTRACT FROM AUTHOR]

Objective: Identifying MRI texture parameters able to distinguish inflammation, fibrosis, and residual cancer in patients with naso-oropharynx carcinoma after radiochemotherapy (RT-CHT). Material and methods: In this single-centre, observational, retrospective study, texture analysis was performed on ADC maps and post-gadolinium T1 images of patients with histological diagnosis of naso-oropharyngeal carcinoma treated with RT-CHT. An initial cohort of 99 patients was selected; 57 of them were later excluded. The final cohort of 42 patients was divided into 3 groups (inflammation, fibrosis, and residual cancer) according to MRI, 18F-FDG-PET/CT performed 3–4 months after RT-CHT, and biopsy. Pre-RT-CHT lesions and the corresponding anatomic area post-RT-CHT were segmented with 3D slicer software from which 107 textural features were derived. T-Student and Wilcoxon signed-rank tests were performed, and features with p-value < 0.01 were considered statistically significant. Cut-off values—obtained by ROC curves—to discriminate post-RT-CHT non-tumoural changes from residual cancer were calculated for the parameters statistically associated to the diseased status at follow-up. Results: Two features—Energy and Grey Level Non-Uniformity—were statistically significant on T1 images in the comparison between 'positive' (residual cancer) and 'negative' patients (inflammation and fibrosis). Energy was also found to be statistically significant in both patients with fibrosis and residual cancer. Grey Level Non-Uniformity was significant in the differentiation between residual cancer and inflammation. Five features were statistically significant on ADC maps in the differentiation between 'positive' and 'negative' patients. The reduction in values of such features between pre- and post-RT-CHT was correlated with a good response to therapy. Conclusions: Texture analysis on post-gadolinium T1 images and ADC maps can differentiate residual cancer from fibrosis and inflammation in early follow-up of naso-oropharyngeal carcinoma treated with RT-CHT. [ABSTRACT FROM AUTHOR]

Aim: To examine the factors that influence meaning in life (MiL) in patients with advanced lung cancer who are undergoing radiochemotherapy. Methods: A cross‐sectional, multivariate stepwise regression analysis and structural equation modeling were used to examine factors influencing MiL in 231 patients with lung cancer in an oncology department of a tertiary hospital in China. Their mood state, family care, social support, and psychological distress were measured. Results: Sex, marital status, and family income significantly affected MiL (p <.05). MiL was significantly correlated (p <.01) with psychological distress (r = −.203), and most significantly (F = 66.883, p <.01; 46.2% of MiL) with mood state (r = −.631), family care (r =.384), and social support (r =.410). Conclusion: To enhance MiL, nurses need to consider patients' mood states and family/social support, as well as tailor patient care toward different sexes and backgrounds. Clinical staff should pay attention to the psychological changes, family care, and social support of patients with advanced lung cancer. [ABSTRACT FROM AUTHOR]