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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/m 2 /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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

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 tumor-surrounding tissue as adjuvant to RCT, but failed to attenuate tumor growth or promote animal survival. [ABSTRACT FROM AUTHOR]

In 2008, the GEC ESTRO Gyn network launched the first multiinstitutional, observational, and prospective international study on MRI-guided brachytherapy in locally advanced cervical cancer patients (EMBRACE-I). EMBRACE-I was followed by EMBRACE-II from 2016 and ongoing. Among the aims of the EMBRACE studies are to benchmark morbidity outcomes and develop dose-volume effects and predictive models for morbidity. The EMBRACE studies collect both physician (CTCAE v.3) and patient (EORTC QLQ-C30/CX24) reported outcomes, including baseline information, in a regular follow-up schedule. The EMBRACE studies feature high numbers of patients (EMBRACE-I N = 1416, EMBRACE-II N = 1500 expected) enrolled from many institutions worldwide (EMBRACE-I n = 23, EMBRACE-II n = 45). This large-scale multiinstitutional approach offers a unique opportunity to investigate and develop new strategies for improving the quality of assessment and reporting of morbidity. This report presents an overview of the challenges and pitfalls regarding the assessment and reporting of morbidity encountered during more than a decade of development and research activities within the EMBRACE consortium. This includes the recognition and evaluation of inconsistencies in the morbidity assessment, and consequently, the provision of assistance and training in the scoring procedure to reduce systematic assessment bias. In parallel, a variety of methodological approaches were tested to comprehensively summarize morbidity outcomes, and a novel approach was developed to refine dose-effect models and risk factor analyses. The purpose of this report is to present an overview of these findings, describe the learning process, and the strategies that have consequently been implemented regarding educational activities, training, and dissemination. [ABSTRACT FROM AUTHOR]

The coronavirus disease (COVID-19) infection, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide. Reports of COVID-19 among cancer patients are limited and most studies focus mainly on its epidemiological and clinical features. In this study, we report the case of a nasopharyngeal cancer patient from Wuhan who contracted COVID-19 during radiochemotherapy and has since recovered from the infection. We hope that this report will provide valuable insight into the treatment of SARS-CoV-2-infected cancer patients through an account of our experience.

Introduction: Smoking has a negative impact on survival of HNSCC patients. In addition, smoking is associated with the prevalence of co-morbidities and, thus, it may be assumed that not smoking per se but co-morbidities impact the course of therapy in terms of lower compliance and dose-reduction. However, data addressing this issue is sparse and conflicting at present, specifically for HNSCCs.Patients and methods: Patient files and tumor documentation from 643 consecutive cases of the University Head and Neck Cancer Centre Kiel were analyzed retrospectively. Patient characteristics and smoking habits were assessed and correlated with co-morbidities and course of treatment.Results: The examined 643 patient files showed that 113 (17.6%), 349 (54.3%), and 180 (28%) patients were never, active, and former smokers, respectively. Three hundred fifteen (49%) were treated by surgery only; 121 (18.8%) received surgery + adjuvant RCT and 72 (11.2%) surgery + adjuvant RT. 111 (17.3%) received primary RCT and 24 (3.7%) primary RT. 131 (20.4%) and 512 (79.6%) had no or had co-morbidities, respectively. Smoking (>10 py) was significantly associated with co-morbidities (p = 0.002). However, smoking and co-morbidities, neither alone nor in combination, were correlated with failure in reaching target doses of radio(chemo)therapy (p > 0.05). Applying (verified) Carlson-Comorbidity-Index (CCI) did not change the results.Conclusions: As expected, smoking is significantly associated with co-morbidities. Dose-reduction of radio(chemo)therapy is as common among active smokers and patients with co-morbidities as among never smokers and patients without co-morbidities. Thus, smoking and co-morbidity seems to impact survival by other means than impairing planned therapy regimens.

In advanced rectal cancer, neoadjuvant radiochemotherapy and total mesorectal excision lead to long overall survival. The quality of life (QOL) of the patients is clearly related to the prognosis. Our question was whether the prognosis can be represented with only one question or one score from the QOL questionnaires. 360 consecutively recruited patients diagnosed with advanced rectal cancer were questioned during radiochemotherapy and a follow-up of 8 years. The questionnaires QLQ-C30 and QLQ-CR38 were used; 10 functional and 17 symptom scores were calculated. The functional score “physical function” and the symptom scores “fatigue”, “nausea and vomiting”, “pain” and “appetite loss” were highly prognostic (p < 0.001) for overall survival. “Physical function” was highly prognostic at all time points up to 1 year after starting therapy (p ≤ 0.001). The baseline “physical function” score divided the cohort into a favorable group with an 8-year overall survival rate of 70.4% versus an unfavorable group with 47.5%. In the multivariable analysis, baseline “physical function”, age and distant metastases were independent predictors of overall survival. The score “physical function” is a powerful unrelated risk factor for overall survival in patients with rectal cancer. Future analyses should study whether increased “physical function” after diagnosis could improve survival.

Abstract Background Despite the combination of surgical resection, radio- and chemotherapy, median survival of glioblastoma multiforme (GBM) patients only slightly increased in the last years. Disease recurrence is definite with no effective therapy existing after tumor removal. Dendritic cell (DC) vaccination is a promising active immunotherapeutic approach. There is clear evidence that it is feasible, results in immunological anti-tumoral responses, and appears to be beneficial for survival and quality of life of GBM patients. Moreover, combining it with the standard therapy of GBM may allow exploiting synergies between the treatment modalities. In this randomized controlled trial, we seek to confirm these promising initial results. Methods One hundred and thirty-six newly diagnosed, isocitrate dehydrogenase wildtype GBM patients will be randomly allocated (1:1 ratio, stratified by O6-methylguanine-DNA-methyltransferase promotor methylation status) after near-complete resection in a multicenter, prospective phase II trial into two groups: (1) patients receiving the current therapeutic “gold standard” of radio/temozolomide chemotherapy and (2) patients receiving DC vaccination as an add-on to the standard therapy. A recruitment period of 30 months is anticipated; follow-up will be 2 years. The primary objective of the study is to compare overall survival (OS) between the two groups. Secondary objectives are comparing progression-free survival (PFS) and 6-, 12- and 24-month OS and PFS rates, the safety profile, overall and neurological performance and quality of life. Discussion Until now, close to 500 GBM patients have been treated with DC vaccination in clinical trials or on a compassionate-use basis. Results have been encouraging, but cannot provide robust evidence of clinical efficacy because studies have been non-controlled or patient numbers have been low. Therefore, a prospective, randomized phase II trial with a sufficiently large number of patients is now mandatory for clear evidence regarding the impact of DC vaccination on PFS and OS in GBM. Trial registration Protocol code: GlioVax, date of registration: 17. February 2017. Trial identifier: EudraCT-Number 2017–000304-14. German Registry for Clinical Studies, ID: DRKS00013248 (approved primary register in the WHO network) and at ClinicalTrials.gov, ID: NCT03395587. Registered on 11 March 2017.

Head and neck squamous cell carcinoma (HNSCC) is among the 10 most common cancers and demonstrates high mortality rates. Well known for its relation to smoking and alcohol consumption, in within the past 10 years a high number of cases, especially of the oropharynx could be shown to be based on an infection of human papilloma virus, high risk subtypes, mostly type 16 and 18. Often it is connected to younger age at onset, better outcome and better response to radiochemotherapy.Next to well established radiochemotherapy schemes, including targeted therapy as cetuximab, in the recent 2 years a complete new therapeutic approach manifested, called checkpoint inhibition. The drugs of this class block a binding of a membranous ligand to a surface receptor on T-cells. Without blocking, this binding is physiological in antigen-presenting cells or many other normal tissue cells (e.g. heart muscle, trophoblast) inhibiting activation of the cytotoxic T-cells. Research revealed an identical way of tumor cells escaping cell death caused by patient’s own immune system. By blocking this inhibition, in several carcinoma entities, a very effective disease control was achieved. So far, 2 pairs of binding are approved for treatment: CD80-CTLA4 and PD1-PDL1. In CD80-CTLA4, it is an inhibitor to CTLA4 (e. g. Ipilimumab), in PD1-PDL1, for both, the ligand an receptor are several inhibitors on the market (e. g. Nivolumab, Pembrolizumab, Atezolizumab, Durvalumab). So far, there could not be found a highly predictive marker for the grade of efficiency of these inhibitors. Next to very recent and complex markers, tumor mutational burden, the immunohistochemical staining for the ligand, PD-L1 could be established in a few number of carcinoma, incuding adenocarcinoma of the lung. Next to different ways of interpretation of the staining, also different staining procedures used in the trials are hindering an easy establishment of this marker in pathology laboratories. The staining procedures used in trials are not comparable with common immunohistochemistry due to very high costs of reagents (test-kits sold by the involved companies, so called companion diagnostic). To overcome these drawbacks, different studies were performed comparing the different antibody clones of immunohistochemical stains used in the official trials and antibodies of other companies. These harmonization studies brought to light that most antibodies stain equally, even the antibodies available from other companies thus making this stain more effordable and possible for introduction in the marker-portfolio of labs of pathology.In HNSCC there is a better response to checkpoint inhibitors in cases of high PD-L1 expression, but also in negative cases, an effect could be seen. The actual approval are exclusively for patients in second line without PD-L1 testing. Upcoming approvals for first line treatment by checkpoint inhibitors are likely to include immunohistochemical testing for PD-L1.

Background and objective Currently, the prognosis of lobectomy and sub-lobectomy for the treatment of stage Ia small cell lung cancer (SCLC) is rarely reported. We retrospectively studied T1N0M0 (≤3 cm) SCLC patients aged ≥60 years, aiming to comparatively analyze the prognosis of lobectomy and sub-lobectomy in treating patients with Ia SCLC. Methods Patients with stage Ia SCLC diagnosed by pathologic between 1992 and 2010 were selected from the “Surveillance, Epidemiology and End Results database”(SEER). Outcome data were compared using Kaplan-Meier (Log-rank test) and Cox model multivariate analysis. Results We identified 515 patients. Median overall survival (OS) of the lobectomy (n=110), sublobar resection (n=57) and non-surgical (n=348) cohort were 45, 23 and 16 months, respectively. The corresponding 5-year OS of the three groups were 44%, 30%, and 14%, respectively. No significant difference in the prognosis of patients with or without lymph node examination/ dissection (P=0.107) and the 5-year OS of patients underwent lobectomy with chemoradiation was 50%. Cox multivariable analysis showed that operation treatment, including lobectomy and sublobectomy, was one of the independent factors associated with the prognosis of early SCLC patients, and patients undergo lobectomy shows a better OS compared with sublobar resection (Lob vs Sub, HR=0.645; 95%CI: 0.433-0.961, P=0.031). Conclusion For age ≥60 years T1N0M0 (≤3 cm) SCLC patients, we recommend anatomical lobectomy combined with adjuvant chemoradiation.

The coronavirus disease (COVID-19) infection, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide. Reports of COVID-19 among cancer patients are limited and most studies focus mainly on its epidemiological and clinical features. In this study, we report the case of a nasopharyngeal cancer patient from Wuhan who contracted COVID-19 during radiochemotherapy and has since recovered from the infection. We hope that this report will provide valuable insight into the treatment of SARS-CoV-2-infected cancer patients through an account of our experience. [ABSTRACT FROM AUTHOR]

• ctDNA can be detected in the majority of patients with locally advanced HNSCC. • ctDNA was correlated with gross tumour volume before treatment start. • Concentration of ctDNA was correlated with treatment response and disease recurrence. • Monitoring of ctDNA/cvDNA is a promising non-invasive biomarker for patients with HNSCC under RCTX. Definitive radiochemotherapy (RCTX) with curative intent is one of the standard treatment options in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Despite this intensive therapy protocol, disease recurrence remains an issue. Therefore, we tested the predictive capacity of liquid biopsies as a novel biomarker during RCTX in patients with HNSCC. We sequenced the tumour samples of 20 patients with locally advanced HNSCC to identify driver mutations. Subsequently, we performed a longitudinal analysis of circulating tumour DNA (ctDNA) dynamics during RCTX. Deep sequencing and UMI-based error suppression for the identification of driver mutations and HPV levels in the plasma enabled treatment-response monitoring prior, during and after RCTX. In 85% of all patients ctDNA was detectable, showing a significant correlation with the gross tumour volume (p -value 0.032). Additionally, the tumour allele fraction in the plasma was negatively correlated with the course of treatment (p -value <0.05). If ctDNA was detectable at the first follow-up, disease recurrence was seen later on. Circulating HPV DNA (cvDNA) could be detected in three patients at high levels, showing a similar dynamic behaviour to the ctDNA throughout treatment, and disappeared after treatment. Monitoring RCTX treatment-response using liquid biopsy in patients with locally advanced HNSCC is feasible. CtDNA can be seen as a surrogate marker of disease burden, tightly correlating with the gross tumour volume prior to the treatment start. The observed kinetic of ctDNA and cvDNA showed a negative correlation with time and treatment dosage in most patients. [ABSTRACT FROM AUTHOR]

Summary: Purpose Galunisertib, a TGF-β inhibitor, has demonstrated antitumor effects in preclinical and radiographic responses in some patients with malignant glioma. This Phase 1b/2a trial investigated the clinical benefit of combining galunisertib with temozolomide-based radiochemotherapy (TMZ/RTX) in patients with newly diagnosed malignant glioma (NCT01220271). Methods This is an open-label, 2-arm Phase 1b/2a study (N = 56) of galunisertib (intermittent dosing: 14 days on/14 days off per cycle of 28 days) in combination with TMZ/RTX (n = 40), versus a control arm (TMZ/RTX, n = 16). The primary objective of Phase 1b was to determine the safe and tolerable Phase 2 dose of galunisertib. The primary objective of Phase 2a was to confirm the tolerability and pharmacodynamic profile of galunisertib with TMZ/RTX, and the secondary objectives included determining the efficacy and pharmacokinetic (PK) profile of galunisertib with TMZ/RTX in patients with glioblastoma. This study also characterized the changes in the major T-cell subsets during TMZ/RTX plus galunisertib treatment. Results In the Phase 2a study, efficacy results for patients treated with galunisertib plus TMZ/RTX or TMZ/RTX were: median overall survival (18.2 vs 17.9 months), median progression-free survival (7.6 vs 11.5 months), and disease control rate (80% [32/40] vs 56% [9/16] patients) respectively. PK profile of galunisertib plus TMZ/RTX regimen was consistent with previously published PK data of galunisertib. The overall safety profile across treatment arms was comparable. Conclusion No differences in efficacy, safety or pharmacokinetic variables were observed between the two treatment arms. [ABSTRACT FROM AUTHOR]

Introduction: Esophageal cancer (EC) is a common malignant tumor entity with increasing occurrence. The incidence of esophageal adenocarcinoma (AC), particularly, is constantly rising in the Western world. The mainstays of therapy with curative intent for EC in advanced stages are neoadjuvant radiochemotherapy (neoRCT) with surgery and definitive radiochemotherapy (defRCT). Methods: We examined our internal files to identify patients suffering from EC. Palliative cases were excluded. Statistical testing was performed by χ2 test, Student's t test, Kaplan-Meier analyses, and the Mann-Whitney U test. Results: One hundred and twenty-two cases were included. Histology revealed squamous cell carcinoma in 92 cases and AC in 23 cases. Ninety-five patients underwent defRCT, 27 underwent neoRCT, and 114 (in both therapy regimes) received simultaneous chemotherapy. There was no difference in the overall survival (OS) (p = 0.654; HR 1.145; 95% CI 0.629–2.086) or and progression-free survival (PFS) (p = 0.912) of patients who underwent neoRCT or defRCT. Median OS was 13.5 (2–197) months for defRCT patients and 19.5 (2–134) months for neoRCT patients (p = 0.751). Karnofsky index (KI) with a cut-off of 70% was strongest, but not a significant parameter for OS (p = 0.608) or PFS (p = 0.137). Conclusion: defRCT is a valid and an equal alternative to neoRCT for patients suffering from EC. Selection of patients for therapy is of crucial relevance. Further studies and improvements in follow-up are needed when neoRCT has been completed before surgery, in order to spare the patient undergoing operative treatment if there is complete remission. The identification of valid markers urgently needed to limit treatment side effects. [ABSTRACT FROM AUTHOR]

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• Focus on pretherapeutic biopsies of patients with oesophageal adenocarcinoma. • Infiltrating inflammatory cells predict response to RCT and prognosis. • FoxP3+ to CD8+ cell-to-cell distance reflects their functional activity. • Results contribute ideas to the TNM-I classification. Tumour infiltrating lymphocytes (TIL) and tumour associated macrophages (TAM) play a key role in anticancer immunosurveillance. We studied their influence on response to neoadjuvant radiochemotherapy (RCT) and prognosis in patients with oesophageal adenocarcinoma (OAC). Between 10/2004 and 06/2018, pre-RCT biopsy-specimens were available from 76 patients with locally advanced, non-metastatic OAC scheduled for trimodality therapy. We evaluated intra- and peritumoural expression of FoxP3+-, CD8+-TIL and CD68+-, CD163+-TAM, contemplating cell density, cell ratios and cell-to-cell distances to determine a possible influence on tumour regression grade (TRG) and survival. Median follow-up time for all patients was 18 months (IQR 9–43), and 54 months (25–97) for surviving patients. Data were analysed using risk analysis, logrank test and Cox regression. Poor tumour regression was detected for cN+ (RR 0.77 [95% CI 0.66–0.90], p = 0.001), low intratumoural FoxP3+/CD8+ ratio (RR 0.75 [0.60–0.96], p = 0.020), high peritumoural CD163+/CD68+ ratio (RR 0.77 [0.60–0.99], p = 0.045) and high intratumoural TAM density (RD −0.44 [−0.82 to −0.06], p = 0.023). Apart from poor resection quality and TRG, pretherapeutic high peritumoural CD8+ infiltration (HR 2.36 [1.21–4.61], p = 0.012) and short intratumoural FoxP3+ to CD8+ cell-to-cell distances in middle ranged CD8+ density (HR 2.55 [1.00–6.52], p = 0.050) were significant unfavourable prognostic factors in multivariate analysis. Immunologic parameters, such as CD8+-, FoxP3+-TIL and CD68+-, CD163+-TAM, were identified to be of independent predictive and prognostic value in patients with OAC. Further and independent validation of these biomarkers by a large size dataset may urgently be contemplated. [ABSTRACT FROM AUTHOR]

OBJECTIVE To determine the prognostic and/or predictive role of 18F-FDG PET/CT parameters, such as SUVmax, SUVmean, Metabolic Tumor Volume (MTV) and Total Lesion Glycolysis (TLG=MTVxSUVmean), for the patients with locally advanced rectal cancer (LARC) treated with neoadjuvant radiotherapy±chemotherapy. METHODS Between January 2005 and December 2016, a total of 106 patients with clinical T3-4 and/or N+ rectal cancer without distant metastasis were included in this study. Correlation between metabolic and volumetric parameters and tumor characteristics was evaluated. Prognostic factors for overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were analyzed. RESULTS The median follow-up duration for all patients was 39.0 months (range, 6-103 months). Pathologic complete response (pCR) was defined as the absence of viable cancer cells in the resected specimen (ypT0N0). pCR was achieved in 17% of all cases (18/106). There was a weak correlation between SUVmax of primary tumor and MTV ([r]=0.238; p<0.001). However, SUVmax of primary tumor and TLG were significantly correlated (r=0.538; p<0.001). Neither SUVmax nor SUVmean was affected by patient and tumor characteristics. Posttreatment extensive stage of disease (p=0.013), absence of concomitant CT (p=0.012), MTV =14.65 cm³ (p=0.008), and TLG =117.00 (p=0.023) were unfavorable prognostic factors for OS on multivariate analysis. CONCLUSION Although FDG-PET is not a standard imaging modality for the treatment of rectal cancers, a negative effect of high MTV and TLG on OS was shown in our study. We should consider more intense treatment approaches for tumors with high MTV and TLG values. [ABSTRACT FROM AUTHOR]

Consolidation immunotherapy with the programmed death ligand 1 (PD-L1) inhibitor durvalumab improves survival in patients with stage III non-small-cell lung cancer responding to radiochemotherapy. The aim of this study was to assess the cost-effectiveness of durvalumab in Switzerland based on the most recent PACIFIC survival follow-up. We constructed a Markov model based on the 3-year follow-up data of the PACIFIC trial and compared consolidation durvalumab with observation. We used published utility values and assessed costs for treatment strategies from the perspective of the Swiss health care payers. Cost-effectiveness was tested both in the intention-to-treat population of the PACIFIC trial unselected for PD-L1 tumor expression and in patients with PD-L1-expressing tumors (≥1%). In the unselected/PD-L1-positive patients, durvalumab showed an incremental effectiveness of 0.76/1.18 quality-adjusted life year (QALY) and incremental costs of Swiss Francs (CHF) 67 239/78 177, resulting in incremental cost-effectiveness ratios of CHF 88 703/66 131 per QALY gained, respectively. The most influential factors for the incremental cost-effectiveness ratio were the utility before first progression, costs for durvalumab, and the hazard ratio for overall survival under durvalumab versus observation. The cost-effectiveness of durvalumab was better than CHF 100 000 per QALY gained in 75% of the simulations in probabilistic sensitivity analysis. Assuming a willingness-to-pay threshold of CHF 100 000 per QALY gained, consolidation durvalumab is likely to be cost-effective both in patients with inoperable stage III non-small-cell lung cancer (NSCLC) unselected for PD-L1 status and in patients with PD-L1-expressing tumors in Switzerland. • Consolidation durvalumab in stage III NSCLC is likely to be cost-effective in Switzerland • Cost-effectiveness was found both for PD-L1 positive (>1%) and for unselected patients • The most influential factors were costs for durvalumab and the utility before disease recurrence • Cost-effectiveness of immunotherapies in NSCLC can be improved if immunotherapies become part of the initial treatment [ABSTRACT FROM AUTHOR]

Background: To determine whether 18F‐PET/CT is able to identify treatment response as early as 1 week after the end of chemoradiotherapy, whether 18F‐PET/CT can identify prognostic markers concerning progression free survival and can identify patients who need additional consolidation therapy. Methods: A total of 54 patients with head and neck cancer were prospectively enrolled in this single‐center, randomized study from 03/2012‐04/2015. Patients underwent FDG‐PET/CT imaging at three predefined time points: pretreatment (PET/CT1), 1 week postprimary radiochemotherapy (PET/CT2) and 3 months postprimary radiochemotherapy (PET/CT3). Tumors were assessed quantitatively based on size and glucose uptake (SUVmax) concerning response at each time point. Response assessment was correlated with progression free survival. All patients had a minimum follow‐up period of 18 months. Multivariate regression analysis was performed to find independent predictors for progression free survival (PFS). Results: Thirty‐two (32) patients (64%) overall remained disease free, 11 patients (22%) had recurrence and 7 patients (14%) had persistent disease. There was no significantly different metabolic parameter ratio found concerning responders and nonresponders at posttreatment (PET/CT2 and 3) time points (P >.05) during clinical follow‐up. Multivariate regression analysis demonstrated both SUVmax and diameter assessed at time point PET/CT3 represent independent predictors of progression free survival (PFS). There was also no statistically significant difference in PFS between responders and nonresponders by means of PET/CT2 in both study arms (P >.05). Imaging responders at time point PET/CT3 showed a significantly longer PFS compared to nonresponders after the end of consolidation therapy (P <.01). Conclusions: Early response of head/neck cancer after radiochemotherapy can be accurately assessed with PET/CT 1 week after RCT. SUVmax and lesion diameter are independent predictors of PFS at time point PET/CT3. PET/CT2 has no prognostic value concerning PFS and cannot identify high risk patients for consolidation therapy. Imaging responders showed a significantly longer PFS compared to nonresponders and therefore PET/CT might serve as a prognostic biomarker. Trial registration: Clinical Trials.gov identifier: NCT01435252. [ABSTRACT FROM AUTHOR]

Background: Preoperative chemoradiotherapy is the recommended standard of care for patients with local advanced rectal cancer. However, it remains unclear, whether a prolonged time interval to surgery results in an increased perioperative morbidity, reduced TME quality or better pathological response. Aim of this study was to determine the time interval for best pathological response and perioperative outcome compared to current recommended interval of 6 to 8 weeks.Methods: This is a retrospective analysis of the German StuDoQ|Rectalcarcinoma registry. Patients were grouped for the time intervals of "less than 6 weeks", "6 to 8 weeks", "8 to 10 weeks" and "more than 10 weeks". Primary endpoint was pathological response, secondary endpoint TME quality and complications according to Clavien-Dindo classification.Results: Due to our inclusion criteria (preoperative chemoradiation, surgery in curative intention, M0), 1.809 of 9.560 patients were suitable for analysis. We observed a trend for increased rates of pathological complete response (pCR: ypT0ypN0) and pathological good response (pGR: ypT0-1ypN0) for groups with a prolonged time interval which was not significant. Ultimately, it led to a steady state of pCR (16.5%) and pGR (22.6%) in "8 to 10" and "more than 10" weeks. We were not able to observe any differences between the subgroups in perioperative morbidity, proportion of rectal extirpation (for cancer of the lower third) or difference in TME quality.Conclusion: A prolonged time interval between neoadjuvant chemoradiation can be performed, as the rate of pCR seems to be increased without influencing perioperative morbidity. [ABSTRACT FROM AUTHOR]

Epithelial mesenchymal crosstalk (EMC) describes the interaction of the tumor stroma and associated fibroblasts with epithelial cancer cells. In this study we analysed the effects of EMC on head and neck cancer cells. In tumor cell lines EMC was induced using media conditioned from a mix-culture of cancer cells and fibroblasts. Cell proliferation and chemotherapy response were assessed using direct cell counting. Flow cytometry, immunohistochemistry of markers of epithelial-mesenchymal transition (EMT) and subsequent TissueFaxs™ acquisition and quantification and western blot analysis were performed. Holotomographic microscopy imaging was used to visualize the effects of EMC on Cisplatin response of SCC-25 cells. EMC induced a hybrid epithelial-mesenchymal phenotype in SCC-25 cells with co-expression of vimentin and cytokeratin. This hybrid phenotype was associated with chemotherapy resistance and increased proliferation of the cells. The EMC conditioned medium led to an activation of the IL-6/STAT3 pathway with subsequent phosphorylation of STAT3. EMC induced a hybrid epithelial-mesenchymal phenotype in HNSCC cells accompanied by increased therapy resistance and cell proliferation. The IL-6/STAT3 pathway might be one of the major pathways involved in these EMC-related effects. [ABSTRACT FROM AUTHOR]

Pineal region tumors represent challenging surgical lesions with wide ranges of survival reported in different surgical series. In this article, we emphasize the role of complete microsurgical resection (CMR) to obtain a favorable long-term outcome of pineal region tumors. We report a retrospective study of pineal region tumors operated on in Helsinki Neurosurgery between 1997 and 2015. Information was obtained from the hospital records, and an evaluation of the Finnish population register was conducted in July 2018 to determine the current status of the patients. A total of 76 pineal region tumors were operated on. The survival was 62% at a mean follow-up of 125 ± 105 months (range, 0–588 months), and the disease-related mortality was limited to 14 patients (18.4%). Up to July 2018, 29 patients had died. Two patients died 1 and 3 months after surgery of delayed thalamic infarctions, 12 patients of disease progression, and 15 had non–disease-related deaths. Only 1 patient was lost in the long-term follow-up. Ten of 14 disease-related deaths occurred during the first 5 years of follow-up: 5 diffuse gliomas, 3 germ cell tumors, 1 grade II–III pineal parenchymal tumor of intermediate differentiation, and 1 meningioma. CMR was linked to better tumor-free survival and long-term survival, with the exception of diffuse gliomas. CMR, in the setting of a multidisciplinary management of pineal region tumors, correlates with favorable survival and with minimal mortality. Surgically treated grade II–IV gliomas constitute a particular group with high mortality within the first 5 years independently of the microsurgical resection. [ABSTRACT FROM AUTHOR]

Emerging evidence has suggested that dysbiosis of the gut microbiota may influence the drug efficacy of colorectal cancer (CRC) patients during cancer treatment by modulating drug metabolism and the host immune response. Moreover, gut microbiota can produce metabolites that may influence tumor proliferation and therapy responsiveness. In this study we have investigated the potential contribution of the gut microbiota and microbial-derived metabolites such as short chain fatty acids and polyamines to neoadjuvant radiochemotherapy (RCT) outcome in CRC patients. First, we established a profile for healthy gut microbiota by comparing the microbial diversity and composition between CRC patients and healthy controls. Second, our metagenomic analysis revealed that the gut microbiota composition of CRC patients was relatively stable over treatment time with neoadjuvant RCT. Nevertheless, treated patients who achieved clinical benefits from RTC (responders, R) had significantly higher microbial diversity and richness compared to non-responder patients (NR). Importantly, the fecal microbiota of the R was enriched in butyrate-producing bacteria and had significantly higher levels of acetic, butyric, isobutyric, and hexanoic acids than NR. In addition, NR patients exhibited higher serum levels of spermine and acetyl polyamines (oncometabolites related to CRC) as well as zonulin (gut permeability marker), and their gut microbiota was abundant in pro-inflammatory species. Finally, we identified a baseline consortium of five bacterial species that could potentially predict CRC treatment outcome. Overall, our results suggest that the gut microbiota may have an important role in the response to cancer therapies in CRC patients.

Neoadjuvant radiochemotherapy with subsequent total mesorectal excision is the standard of care for locally advanced rectal cancer. While this multimodal strategy has decreased local recurrences rates below 5%, long-term morbidities are considerable in terms of urinary, sexual or bowel functioning. At the same time approximately 10–20% of patients have no evidence of residual tumour in their surgical specimen. Pioneering studies from Brazil have suggested that surgery can safely be omitted in carefully selected patients with a clinical complete response after radiochemotherapy. Although confirmatory studies showed similar results, challenges in terms of optimizing radiochemotherapy for organ-preservation, appropriate selection of patients for non-operative management and the safety of this approach remain. The present review will summarize the current data on organ-preservation in rectal cancer and discuss the challenges that need to be addressed in future trials.

Background: Hypofractionated radiotherapy (HFR) is sometimes used in the treatment of glioblastoma multiforme (GBM). The efficacy and safety of HFR is still under investigation. The aim of this systematic review and meta-analysis was to provide a comprehensive summary of the efficacy and safety of HFR, and to compare the efficacy and safety of HFR and conventional fraction radiotherapy (CFR) for the treatment of patients with GBM, based on the results of randomized controlled trials (RCTs).Methods: A literature search was conducted to identify Phase II and III trials o comparing the efficacy and safety of HFR and CFR. Study selection, data extraction, and quality assessment, were conducted by two independent researchers. The analysis was performed using RevMan 5.3 and Stata 12.0.Results: Sixteen Phase II and III trials were included in the systematic review, and four RCTs were included in the meta-analysis. Participants treated with HRF and CRF had comparable overall survival (OS) (hazard ratio [HR]: 0.94, 95% confidence interval [CI]: 0.72–1.22, P = 0.64) and progression-free survival (PFS) (HR: 1.09, 95% CI: 0.60–1.95, P = 0.79), and similar rates of adverse events. However, in participants aged >70 years, those who received HFR had a higher OS than those who received CFR (HR: 0.59, 95% CI: 0.37–0.93, P = 0.02).Conclusions: HRF is efficacious and safe for the treatment of GBM. In individuals aged >70 years, treatment with HRF is superior to CFR in terms of OS. The role of HFR in the treatment of GBM in younger individuals and those with good prognostic factors requires further research.

Background: Intra-tumoral CD8 + T-cell infiltration in squamous cell carcinoma of the head and neck (HNSCC) has previously been linked to the efficacy of cisplatin-based chemoradiation (CDDP-CRTX) and immune checkpoint inhibitor (ICI) monotherapy. Further detailed characterization of the tumor immune-micromilieu and its influence on outcome may guide the development of CRTX-ICI combinations. Methods: Comprehensive immune transcriptome analysis was applied to a training set of tumor specimens from oropharyngeal squamous cell carcinoma (OPSCC) patients treated with CDDP-CRTX in the ARO-0401 phase III study (n = 33). A composite immune signature risk score (ISRS) for survival prediction was developed, and subsequently validated in two independent OPSCC cohorts treated with either CDDP-CRTX (n = 36) or mitomycin-based CRTX (MMC-CRTX, n = 31). Further validation of the ISRS was performed in the OPSCC subset (n = 79) of the TCGA HNSCC cohort. Potential interference between immune signatures and HPV status was evaluated in multivariate Cox regression models. Results: Significant differences according to the 3-y OS status in the abundance of tumor-infiltrating T- and B-cells, and the expression levels of 51 immune-related genes were observed. A risk score based on 13 differentially expressed genes involved in cytokine signaling, T-cell effector functions and the TNFR pathway was established as robust predictive factor of OS. Its predictive power was superior to the 6-gene interferon-gamma signature of ICI efficacy and independent of the HPV status. Conclusions: This study further elucidates the complex interaction of the tumor immune microenvironment with the efficacy of CDDP-CRTX in OPSCC. The results suggest immune markers for selection of patients treated with CRTX-ICI combinations.

Organ preservation after a clinical complete response to radiochemotherapy is currently one of the most discussed topics in the management of rectal cancer. However, the patients' perspective has only been poorly studied so far. In this multicenter study, we examined 49 patients with locally advanced rectal cancer. The willingness to participate in an organ preservation study and the acceptance of the associated aspects such as intensified radiochemotherapy protocols, the need for close follow-up examinations and local regrowth rates were assessed. Attitudes were correlated with baseline quality of life parameters and psychological scales for “fear of progression”, “locus of control”, “depression”, and the “willingness to take risks”. A total of 83% of patients would consider the deferral of surgery in case of a clinical complete response (cCR). Three monthly follow-up studies and a 25% local regrowth rate are considered acceptable by 95% and 94% respectively. While 41% would be willing to exchange cure rates for a non-operative treatment strategy, a potentially more toxic radiochemotherapy in order to increase the probability of a cCR was the aspect with the lowest acceptance (55%). Psychological factors, in particular “locus of control” and “willingness to take risks”, influenced patient preferences regarding most of the assessed parameters. While in general a broad acceptance of an organ-preserving treatment can be expected, patient preferences and concerns regarding different aspects of this strategy vary widely and require specific consideration during shared decision making.

Neoadjuvant radiochemotherapy (nRCT) can significantly influence the tumor immune architecture that plays a pivotal role in regulating tumor growth. Whereas, various studies have investigated the effect of nRCT on tumor-infiltrating T cells, little is known about its impact on the frequency and activation status of human dendritic cells (DCs). Plasmacytoid DCs (pDCs) essentially contribute to the regulation of innate and adaptive immunity and may profoundly influence tumor progression. Recent studies have revealed that higher pDC numbers are associated with poor prognosis in cancer patients. 6-sulfo LacNAc-expressing monocytes (slanMo) represent a particular proinflammatory subset of human non-classical blood monocytes that can differentiate into DCs. Recently, we have reported that activated slanMo produce various proinflammatory cytokines and efficiently stimulate natural killer cells and T lymphocytes. slanMo were also shown to accumulate in clear cell renal cell carcinoma (ccRCC) and in metastatic lymph nodes from cancer patients. Here, we investigated the influence of nRCT on the frequency of rectal cancer-infiltrating pDCs and slanMo. When evaluating rectal cancer tissues obtained from patients after nRCT, a significantly higher density of pDCs in comparison to pre-nRCT tissue samples was found. In contrast, the density of slanMo was not significantly altered by nRCT. Further studies revealed that nRCT significantly enhances the proportion of rectal cancer-infiltrating CD8+ T cells expressing the cytotoxic effector molecule granzyme B. When exploring the impact of nRCT on the phenotype of rectal cancer-infiltrating pDCs and slanMo, we observed that nRCT markedly enhances the percentage of inducible nitric oxide synthase (iNOS)- or tumor necrosis factor (TNF) alpha-producing slanMo. Furthermore, nRCT significantly increased the percentage of mature CD83+ pDCs in rectal cancer tissues. Moreover, the proportion of pDCs locally expressing interferon-alpha, which plays a major role in antitumor immunity, was significantly higher in post-nRCT tissues compared to pre-nRCT tumor specimens. These novel findings indicate that nRCT significantly influences the frequency and/or phenotype of pDCs, slanMo, and CD8+ T cells, which may influence the clinical response of rectal cancer patients to nRCT.

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.

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.

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., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Discrete organometallic complexes with defined structures are proceeding rapidly in combating malignant tumors due to their multipronged treatment modalities. Many innovative superiorities, such as high antitumor activity, extremely low systemic toxicity, active targeting ability, and enhanced cellular uptake, make them more competent for clinical applications than individual precursors. In particular, coordination-induced regulation of luminescence and photophysical properties of organic light-emitting ligands has demonstrated significant potential in the timely evaluation of therapeutic efficacy by bioimaging and enabled synergistic photodynamic therapy (PDT) or photothermal therapy (PTT). This review highlights instructive examples of multimodal radiochemotherapy platforms for cancer ablation based on self-assembled metallacycles/metallacages, which would be classified by functions in a progressive manner. Finally, the essential demands and some plausible prospects in this field for cancer therapy are also presented., (© 2023 Wiley-VCH GmbH.)

We developed machine and deep learning models to predict chemoradiotherapy in rectal cancer using 18 F-FDG PET images and harmonized image features extracted from 18 F-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 18 F-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 18 F-FDG PET images must be harmonized to demonstrate reproducibility with external data. Harmonized 18 F-FDG PET image features as an element of machine learning could help predict chemoradiotherapy responses in external tests with reproducibility.

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., (© 2023. The Author(s).)

MicroRNAs (miRs) are non-coding master regulators of transcriptome that could act as tumor suppressors (TSs) or oncogenes (oncomiRs). We aimed to systematically investigate the relevance of miRs as prognostic biomarkers in primary glioblastoma multiforme (GBM) treated with postoperative radio(chemo)therapy (PORT). For hypothesis generation, tumor miR expression by Agilent 8x15K human microRNA microarrays and survival data from 482 GBM patients of The Cancer Genome Atlas (TCGA cohort) were analyzed using Cox-PH models. Expression of candidate miRs with prognostic relevance (miR-221/222; miR-17-5p, miR-18a, miR-19b) was validated by qRT-PCR using Taqman technology on an independent validation cohort of GBM patients (n = 109) treated at Heidelberg University Hospital (HD cohort). In TCGA, 50 miRs showed significant association with survival. Among the top ranked prognostic miRs were members of the two miR families miR-221/222 and miR-17-92. Loss of miR-221/222 was correlated with improved prognosis in both cohorts (TCGA, HD) and was an independent prognostic marker in a multivariate analysis considering demographic characteristics (age, sex, Karnofsky performance index (KPI)), molecular markers (O-6-methylguanine-DNA methyltransferase (MGMT) methylation, IDH mutation status) and PORT as co-variables. The prognostic value of miR-17-92 family members was ambiguous and in part contradictory by direct comparison of the two cohorts, thus warranting further validation in larger prospective trials.

Background and Objectives: Despite advances in treatment, local recurrence remains a great concern in patients with rectal cancer. The aim of this study was to investigate the incidence and risk factors of local recurrence of rectal cancer in our single center over a 7-year-period. Materials and Methods: Patients with stage I-III rectal cancer were treated with curative intent. The necessity for radiotherapy and chemotherapy was determined before surgery and/or postoperative histopathological results. Results: Of 365 rectal cancer patients, 76 (20.8%) developed recurrent disease. In total, 27 (7.4%) patients presented with a local tumor recurrence (isolated in 40.7% of cases). Radiotherapy was performed in 296 (81.1%) patients. The most often used schema was 5 × 5 Gy followed by immediate surgery (n = 214, 58.6%). Local recurrence occurred less frequently in patients treated with 5 × 5 Gy radiotherapy followed by surgery (n = 9, 4%). Surgical procedures of relapses were performed in 12 patients, six of whom were operated with radical intent. Only two (7.4%) patients lived more than 5 years after local recurrence treatment. The incidence of local recurrence was associated with primary tumor distal location and worse prognosis. The median overall survival of patients after local recurrence treatment was 19 months. Conclusions: Individualized rectal cancer patient selection and systematic treatment algorithms should be used clinical practice to minimize likelihood of relapse. 5 × 5 Gy radiotherapy followed by immediate surgery allows good local control in resectable cT2N+/cT3N0 patients. Radical resection of isolated local recurrence offers the best chances of cure.

Background and Objective: Investigations on the clinical impact of supraclavicular lymph node (SCN) involvement in stage IIIC non-small cell lung cancer (NSCLC) remain scarce. We evaluated the oncological outcomes of definitive radiochemotherapy and the clinical significance of SCN involvement. Materials and Methods: Between November 2009 and June 2019, a total of 40 patients with N3-positivity and NSCLC were evaluated. Most patients received concomitant chemotherapy, but six patients who received radiotherapy (RT) alone were also included. Twenty-one patients (52.5%) received 3D-conformal RT (3DCRT), and the remainder received intensity-modulated RT (IMRT). Results: The median follow-up duration was 10.7 months (range: 1.7–120.6 months). Median overall survival (OS) and cause-specific survival (CSS) times were 10.8 months and 16.3 months, respectively. Among the 40 patients, 17 (42.5%) had SCN involvement. SCN involvement negatively affected progression-free survival (hazard ratio (HR): 2.08, 95% confidence interval (CI): 1.04–4.17, p = 0.039) and local control (HR: 3.05, 95% CI: 1.09–8.50, p = 0.034). However, IMRT use was correlated with higher local control (HR: 0.28, 95% CI: 0.09–0.86, p = 0.027). Grade ≥3 esophagitis and pneumonitis accounted for 7.5% and 15.0% of all cases, respectively. A higher RT dose (mean dose: 66.6 vs. 61.7 Gy) was significantly correlated with grade ≥3 pneumonitis (p = 0.001). RT modality was a significant factor (p = 0.042, five of six cases occurred in the IMRT group). Conclusions: SCN involvement could negatively affect oncologic outcomes of stage IIIC NSCLC patients. High-dose irradiation with IMRT could increase local control but may cause lung toxicities.

Peripheral blood leukocytosis and neutrophilia reflect cancer inflammation and have been proposed as prognostic immunological biomarkers in various malignancies. However, previous studies were limited by their retrospective nature and small patient numbers. Baseline peripheral blood leukocytes, neutrophils, hemoglobin, platelets, lactate dehydrogenase and carcinoembryonic antigen (CEA) were correlated with clinicopathologic characteristics, and clinical outcome in 1236 patients with rectal cancer treated with 5‐FU‐based preoperative chemoradiotherapy (CRT) alone or with oxaliplatin followed by surgery and adjuvant chemotherapy within the CAO/ARO/AIO‐04 randomized phase 3 trial. Multivariable analyses were performed using Cox regression models. After a median follow‐up of 50 months, baseline leukocytosis remained an independent adverse prognostic factor for disease‐free survival (DFS; HR 1.457; 95% CI 1.163–1.825; p = 0.001), distant metastasis (HR 1.696; 95% CI 1.266–2.273; p < 0.001) and overall survival (OS; HR 1.716; 95% CI 1.264–2.329; p = 0.001) in multivariable analysis. Similar significant findings were observed for neutrophilia and high CEA levels. Conversely, treatment‐induced leukopenia correlated with favorable DFS (p = 0.037), distant metastasis (p = 0.028) and OS (p = 0.012). Intriguingly, addition of oxaliplatin to 5‐FU CRT resulted in a significant DFS improvement only in patients with neutrophilia and leukocytosis (p = 0.028 and p = 0.002). Our findings have important clinical implications and provide high‐level evidence on the adverse prognostic role of leukocytes and neutrophils, and the impact of chemotherapy in the context of these biomarkers. These data could help guide patient stratification and should be further validated within prospective studies. What's new? Cancer often causes an inflammatory response, recruiting leukocytes and neutrophils to the tumor site where they hinder anti‐cancer treatments. Here, the authors asked how leukocytosis and neutrophilia affect outcomes in rectal cancer. Unlike previous studies, which have been retrospective, this study examined a large cohort of patients within a phase 3 clinical trial. They found that baseline leukocytosis and neutrophilia independently predicted poor outcomes, including distant metastasis and shorter survival. Treatment‐induced leukopenia, meanwhile, correlated with better outcomes. Adding oxaliplatin to standard chemoradiation improved disease‐free survival only in those patients with leukocytosis & neutrophilia. These findings could lead to improved personalized treatments. [ABSTRACT FROM AUTHOR]

Background: Hypofractionated radiotherapy (HFR) is sometimes used in the treatment of glioblastoma multiforme (GBM). The efficacy and safety of HFR is still under investigation. The aim of this systematic review and meta-analysis was to provide a comprehensive summary of the efficacy and safety of HFR, and to compare the efficacy and safety of HFR and conventional fraction radiotherapy (CFR) for the treatment of patients with GBM, based on the results of randomized controlled trials (RCTs). Methods: A literature search was conducted to identify Phase II and III trials o comparing the efficacy and safety of HFR and CFR. Study selection, data extraction, and quality assessment, were conducted by two independent researchers. The analysis was performed using RevMan 5.3 and Stata 12.0. Results: Sixteen Phase II and III trials were included in the systematic review, and four RCTs were included in the meta-analysis. Participants treated with HRF and CRF had comparable overall survival (OS) (hazard ratio [HR]: 0.94, 95% confidence interval [CI]: 0.72–1.22, P = 0.64) and progression-free survival (PFS) (HR: 1.09, 95% CI: 0.60–1.95, P = 0.79), and similar rates of adverse events. However, in participants aged >70 years, those who received HFR had a higher OS than those who received CFR (HR: 0.59, 95% CI: 0.37–0.93, P = 0.02). Conclusions: HRF is efficacious and safe for the treatment of GBM. In individuals aged >70 years, treatment with HRF is superior to CFR in terms of OS. The role of HFR in the treatment of GBM in younger individuals and those with good prognostic factors requires further research. [ABSTRACT FROM AUTHOR]

Background: Current guidelines recommend neoadjuvant therapy for patients with stage II or III rectal cancer. The addition of platinum derivatives to fluoropyrimidine-based chemoradiotherapy has been frequently investigated, but their role in this setting remains controversial.Methods: PubMed, Cochrane Library, and Web of Science were systematically searched for randomized trials comparing chemoradiotherapy with or without platinum agents in stage II or III rectal cancer. Main outcome parameters were overall and disease-free survival, additional outcomes included pathological complete response, isolated local recurrence, distant recurrence, toxicity, and perioperative morbidity. Time-to-event data were pooled as hazard ratios (HRs) by the inverse variance method and binary outcomes as odds ratios (ORs) by the Peto method with their respective 95% confidence interval (CI). All statistical tests were two-sided.Results: Ten randomized controlled trials with data on 5599 patients were included in the meta-analysis. Platinum derivatives did not statistically significantly improve overall survival (HR = 0.93, 95% CI = 0.82 to 1.05, P = .23), disease-free survival (HR = 0.91, 95% CI = 0.83 to 1.01, P = .07), or local recurrence (OR = 0.83, 95% CI = 0.66 to 1.05, P = .12). However, it led to a statistically significant increase of pathological complete response (OR = 1.31, 95% CI = 1.10 to 1.55, P = .002) and a statistically significant reduction of distant recurrence (OR = 0.78, 95% CI = 0.66 to 0.92, P = .004). Benefits were accompanied by higher rates of grade 3 or 4 toxicities.Conclusions: Intensified neoadjuvant chemoradiotherapy with the addition of platinum derivatives cannot be recommended routinely because it did not improve overall or disease-free survival and was associated with increased toxicity. It needs to be elucidated whether the benefits in distant recurrence and pathological complete response may be advantageous for selected high-risk patients. [ABSTRACT FROM AUTHOR]

Background: Oropharyngeal squamous carcinoma (OPSC) continues to increase in incidence secondary to human papillomavirus (HPV) infection. Despite the good overall prognosis for these patients, treatment with chemoradiation is associated with morbidity and treatment failure. Better predictors for disease outcome are needed to guide de-intensification regimens. We hypothesized that estrogen receptor α (ERα), a prognostic biomarker in oncology with therapeutic implications, might have similar utility in OPSC.Methods: To investigate associations among ERα and demographics, HPV status, and survival, we analyzed ERα mRNA expression of head and neck squamous carcinomas (HNSC) from The Cancer Genome Atlas (TCGA) and immunohistochemistry (IHC) of pretreatment biopsy specimens from an independent group of 215 OPSC patients subsequently treated with primary chemoradiation (OPSC-CR). Associations among variables were evaluated with Fisher exact tests and logistic regression; associations with survival were evaluated with log-rank tests and Cox proportional hazards regression.Results: Among 515 patients in TCGA, ERα mRNA expression was highest in HPV-positive OPSC. High ERα mRNA expression was associated with improved survival among those receiving chemoradiation (hazard ratio adjusted for HPV status = 0.44, 95% confidence interval = 0.21 to 0.92). In OPSC-CR, ERα was positive by IHC in 51.6% of tumors and was associated with improved overall, disease-specific, progression-free, and relapse-free survival (log-rank tests: P < .001, P < .001, P = .002, P = .003, respectively); statistically significant associations of ERα positivity with improved survival were maintained after adjusting for clinical risk factors including HPV status.Conclusion: In two independent cohorts, ERα is a potential biomarker for improved survival that also may represent a therapeutic target in OPSC. [ABSTRACT FROM AUTHOR]