Clinicopathological and genetic characterization of radiotherapy-induced undifferentiated pleomorphic sarcoma following breast cancer: a case series of three tumors and comprehensive literature review.

AIMS: Compared to primary breast sarcoma (BSs), radiotherapy-induced sarcoma (RIS) is a less frequent type of secondary breast sarcoma. Undifferentiated pleomorphic sarcoma (UPS) is an even rarer occurrence within the RIS category. This study aimed to present the clinicopathologic and molecular features of breast radiotherapy-induced UPS. METHODS: A retrospective study was conducted at the Third Affiliated Hospital of Soochow University to analyze three patients with radiation-induced undifferentiated pleomorphic sarcoma (UPS) following breast cancer, spanning from 2006 to 2023. The clinical and pathological variables were extracted from the medical records, while immunohistochemistry was employed to analyze the immunophenotypes of these tumors. Genomic characteristics were assessed through DNA and RNA sequencing techniques. Another 15 cases from the literature were also reviewed to better characterize the tumor. RESULTS: The affected areas encompass the chest wall and breasts, with an incubation period ranging from 6 to 17 years. The tumor cells exhibit pleomorphism and demonstrate a high degree of pathological mitosis. Notably, two cases displayed an accelerated disease progression, characterized by recurrent tumors and metastases occurring within short intervals of 48 and 7 months respectively subsequent to the initial diagnosis. The two prevailing identified genes were TP53 (2/3, 66.7%) and RB1 (1/3, 33.3%). Through analysis of somatic copy number variation (CNV), it was discovered that two oncogenes, MCL1 (1/3, 33.3%) and MYC (1/3, 33.3%), had experienced gains in CNV. The Tumor Mutational Burden (TMB) values for case 1, case 2, and case 3 were 5.9 mut/Mb, 1.0 mut/Mb, and 3.0 mut/Mb, respectively. Moreover, the analysis of RNA-NGS (next-generation sequencing) revealed the presence of a novel gene fusion, named COL3A1-GULP1, in case 2. CONCLUSIONS: Based on our thorough analysis of research findings and previous reports, it is evident that radiotherapy-induced UPS exhibits a highly diverse and frequently severe clinical and biological behavior. Identifying tumor formation using genome sequencing can help understand its biological behavior and determine personalized treatments.

Causes of missed MRI diagnosis of radiotherapy-induced temporal lobe injury in nasopharyngeal carcinoma. / MRIæ£€æŸ¥é¼»å’½ç™Œæ”¾å°„æ€§é¢žå¶æŸä¼¤çš„æ¼è¯ŠåŽŸå› .

OBJECTIVES: Radiotherapy is the primary treatment for nasopharyngeal carcinoma, but it frequently leads to radiotherapy-induced temporal lobe injury (RTLI). Magnetic resonance imaging (MRI) is the main diagnostic method for RTLI after radiotherapy for nasopharyngeal carcinoma, but it is prone to missed diagnoses. This study aims to investigate the causes of missed diagnoses of RTLI in nasopharyngeal carcinoma patients undergoing MRI after radiotherapy. METHODS: Clinical and MRI data from nasopharyngeal carcinoma patients diagnosed and treated with radiotherapy at Xiangya Hospital of Central South University, from January 2010 to April 2021, were collected. Two radiologists reviewed all head and neck MRIs (including nasopharyngeal and brain MRIs) before and after radiotherapy of identify cases of late delayed response-type RTLI for the first time. If the original diagnosis of the initial RTLI in nasopharyngeal carcinoma patients did not report temporal lobe lesions, it was defined as a missed diagnosis. The first diagnosis of RTLI cases was divided into a missed diagnosis group and a non-missed diagnosis group. Clinical and imaging data were compared between the 2 groups, and multivariate logistic regression analysis was used to identify independent risk factors for MRI missed diagnoses of initial RTLI. RESULTS: A total of 187 nasopharyngeal carcinoma with post-radiotherapy RTLI were included. The original diagnostic reports missed 120 cases and accurately diagnosed 67 cases, with an initial RTLI diagnosis accuracy rate of 35.8% and a missed diagnosis rate of 64.2%. There were statistically significant differences between the missed diagnosis group and the non-missed diagnosis group in terms of lesion size, location, presence of contralateral temporal lobe lesions, white matter high signal, cystic degeneration, hemorrhage, fluid attenuated inversion recovery (FLAIR), and examination site (all P<0.05). Multivariate logistic regression analysis showed that lesions ≤25 mm, non-enhancing lesions, lesions without cystic degeneration or hemorrhage, lesions located only in the medial temporal lobe, and MRI examination only of the nasopharynx were independent risk factors for missed MRI diagnosis of initial RTLI (all P<0.05). CONCLUSIONS: The missed diagnosis of initial RTLI on MRI is mainly related to lesion size and location, imaging characteristics, and MRI examination site.

Intercellular pathways of cancer treatment-related cardiotoxicity and their therapeutic implications: the paradigm of radiotherapy.

Advances in cancer therapeutics have improved patient survival rates. However, cancer survivors may suffer from adverse events either at the time of therapy or later in life. Cardiovascular diseases (CVD) represent a clinically important, but mechanistically understudied complication, which interfere with the continuation of best-possible care, induce life-threatening risks, and/or lead to long-term morbidity. These concerns are exacerbated by the fact that targeted therapies and immunotherapies are frequently combined with radiotherapy, which induces durable inflammatory and immunogenic responses, thereby providing a fertile ground for the development of CVDs. Stressed and dying irradiated cells produce 'danger' signals including, but not limited to, major histocompatibility complexes, cell-adhesion molecules, proinflammatory cytokines, and damage-associated molecular patterns. These factors activate intercellular signaling pathways which have potentially detrimental effects on the heart tissue homeostasis. Herein, we present the clinical crosstalk between cancer and heart diseases, describe how it is potentiated by cancer therapies, and highlight the multifactorial nature of the underlying mechanisms. We particularly focus on radiotherapy, as a case known to often induce cardiovascular complications even decades after treatment. We provide evidence that the secretome of irradiated tumors entails factors that exert systemic, remote effects on the cardiac tissue, potentially predisposing it to CVDs. We suggest how diverse disciplines can utilize pertinent state-of-the-art methods in feasible experimental workflows, to shed light on the molecular mechanisms of radiotherapy-related cardiotoxicity at the organismal level and untangle the desirable immunogenic properties of cancer therapies from their detrimental effects on heart tissue. Results of such highly collaborative efforts hold promise to be translated to next-generation regimens that maximize tumor control, minimize cardiovascular complications, and support quality of life in cancer survivors.

Quantitative assessment of breast volume changes after whole-breast irradiation for breast cancer using breast auto-segmentation.

PURPOSE: This study aimed to quantitatively estimate the changes in breast volume associated with radiotherapy in patients undergoing breast-conserving surgery and whole-breast irradiation (WBI). METHODS: Pre-WBI simulation computed tomography (CT) scans and post-WBI follow-up chest CT scans from a total of 1,151 breast cancer patients were analyzed using a deep-learning-driven auto-segmentation approach. The CT-based asymmetry index (CTAI) was calculated by dividing the volume of the irradiated breast by the volume of the contralateral breast. Significant breast shrinkage was defined as a CTAI < 0.85. To quantify changes in CTAI over the follow-up period, the CTAI ratio was determined as the post-WBI CTAI divided by the pre-WBI CTAI. A multivariate logistic regression analysis was conducted to identify potential variables associated with post-WBI significant breast shrinkage. RESULTS: The median CTAI values for pre- and post-WBI CT scans were 0.973 (interquartile range: 0.887-1.069) and 0.866 (interquartile range: 0.773-0.967), respectively. The difference between them was statistically significant (p < 0.001). Following WBI, there was an increase in the rate of significant breast shrinkage from 16.3 to 44.8%. The CTAI ratio showed a negative association with the time interval (p < 0.001, Pearson r = - 0.310). In the multivariate logistic regression analysis, lower pre-WBI CTAI, younger age, and longer interval between CT scans were found to be significantly associated with a higher occurrence of post-WBI significant breast shrinkage. CONCLUSION: Breast volume decreases following WBI, and this decrease is correlated with an increased duration after WBI. These findings highlight the long-term consequences of WBI on breast asymmetry.

Rare case of radiotherapy-induced angiosarcoma (RIAS) after conservative and radical treatment of breast cancer: About two cases and review of the literature.

INTRODUCTION AND IMPORTANCE: Angiosarcoma of the breast is a rare malignant tumour of endothelial origin. It is characterised by a high degree of malignancy and a polymorphous clinical and radiological presentation, a source of diagnostic error and delay. It has a very poor prognosis. Mammary angiosarcoma is a rare but formidable complication of radiotherapy. The specificity of this observation is that we are presenting two clinical cases of different surgical management of breast cancer who suffered the same complication from radiotherapy. CASE PRESENTATION: We report two cases of Radiotherapy-induced angiosarcoma (RIAS) in two patients with a history of breast cancer one treated by conservative surgery and radiotherapy and the other by radical surgery and radiotherapy both patients were operated. CLINICAL DISCUSSION: Radiotherapy-induced angiosarcoma (RIAS) is a rare complication of radiotherapy. The increasing use of conservative treatment of breast cancer, which combines surgery with radiotherapy and chemotherapy, can rarely be complicated by breast sarcoma. CONCLUSION: The natural history of radiation-induced angiosarcoma is more or less rapid, with death occurring in the setting of metastatic spread after a median survival of 24 months. The quality of the surgical procedure is a prognostic factor.

Sodium-hyaluronate mouthwash on radiotherapy-induced xerostomia: a randomised clinical trial.

INTRODUCTION: Radiotherapy-induced xerostomia (RIX) is one of the most common adverse effects of radiotherapy (RT) in head and neck cancer patients (HNC) and a major determinant of survivors' quality of life. The primary objective was to evaluate the reduction of patients' xerostomia symptoms after the utilisation of a sodium-hyaluronate mouthwash compared to a placebo solution. The secondary objectives were to evaluate the improvement of quality of life and to evaluate the patients' satisfaction. METHODS: The protocol was approved by the ethical committee (Ref. 50,053/19) and registered at ClinicalTrials.gov (ID: NCT05103124). The study was a double-blind randomised clinical trial (RCT) with a crossover design and was conducted at the Fondazione Policlinico Universitario A. Gemelli, Rome. RESULTS: Thirty-two patients completed the study protocol. Lower values of the modified Xerostomia Questionnaire (XQ) were retrieved when comparing the baseline scores to the ones after the treatment, when compared with placebo (Mann-Whitney U test = 0.01); higher values of patients' satisfaction (Likert scale) and modified XQ were retrieved for the sodium-hyaluronate mouthwash (Mann-Whitney U test = 0.001). CONCLUSIONS: This RCT highlights the advantages of treating RIX with the sodium-hyaluronate mouthwash since it seems to be clinically effective in reducing its symptoms, without any reported adverse events. CLINICALTRIALS: gov: NCT05103124 in 17/10/2021.

Radiotherapy-Induced Neurocognitive Dysfunction in Brain Tumor Survivors: Burden and Rehabilitation.

Radiotherapy-induced neurocognitive dysfunction after cranial irradiation has an incidence of 40-100%. It may affect both children and adults, and represents a significant burden not only on ill individuals and their caregivers but also on the health care system and society in general. Multiple patient-, tumor-, and treatment-related factors may contribute to development of this complication, but its pathophysiological mechanisms are still not understood clearly. It is hoped that introduction of more advanced techniques for conformal irradiation, optimized dosimetry, and specific prophylactic measures will decrease the risk of neurocognitive decline in brain tumor survivors in the future.

Polyphenols as Potential Protectors against Radiation-Induced Adverse Effects in Patients with Thoracic Cancer.

Radiotherapy is one of the standard treatment approaches used against thoracic cancers, occasionally combined with chemotherapy, immunotherapy and molecular targeted therapy. However, these cancers are often not highly sensitive to standard of care treatments, making the use of high dose radiotherapy necessary, which is linked with high rates of radiation-induced adverse effects in healthy tissues of the thorax. These tissues remain therefore dose-limiting factors in radiation oncology despite recent technological advances in treatment planning and delivery of irradiation. Polyphenols are metabolites found in plants that have been suggested to improve the therapeutic window by sensitizing the tumor to radiotherapy, while simultaneously protecting normal cells from therapy-induced damage by preventing DNA damage, as well as having anti-oxidant, anti-inflammatory or immunomodulatory properties. This review focuses on the radioprotective effect of polyphenols and the molecular mechanisms underlying these effects in the normal tissue, especially in the lung, heart and esophagus.

The regulation of expression and splicing of transcription factors are related to the muscle damage caused by radiation in tree shrews.

Radiotherapy-induced muscle injury (RIMI) is a major complication of radiotherapy for nasopharyngeal carcinoma. Transcription factor (TF) expression and alternative splicing are crucial events in transcriptional and posttranscriptional regulation, respectively, and are known to be involved in key signaling pathways contributing to a variety of human disorders, including radiation injury. To investigate the TFs and alternative splicing events involved in RIMI, we constructed a tree shrew model as described previously in which the RIMI group received 20 Gy of irradiation on the tensor veli palatini (TVP) muscles. The irradiated muscles were evaluated by RNA sequencing (RNA-seq) 6 months later, and the results compared with those for normal TVP muscles. The alt5p and alt3p events were the two main types of differentially regulated alternative splicing events (RASEs) identified via the Splice sites Usage Variation Analysis (SUVA) software, and these RASEs were highly conserved in RIMI. According to functional enrichment analysis, the differentially RASEs were primarily enriched in pathways related to transcriptional regulation. Furthermore, we identified 16 alternative splicing TFs (ASTFs) in ASTF-differentially expressed gene (DEG) networks based on co-expression analysis, and the regulatory networks were chiefly enriched in pathways linked to cell proliferation and differentiation. This study revealed that RASEs and ASTF-DEG networks may both play important regulatory roles in gene expression network alteration in RIMI. Future studies on the targeting mechanisms and early interventions directed at RASEs and ASTF-DEG networks may aid in the treatment of RIMI.

Efficacy of curcumin for amelioration of radiotherapy-induced oral mucositis: a preliminary randomized controlled clinical trial.

BACKGROUND: Oral mucositis (OM) is one of the main problems in almost all patients undergoing head and neck radiotherapy (RT). Owning to the antioxidant and anti-inflammatory properties of curcumin, the effect of both oral and topical formulations of curcumin was assessed on radiation-induced OM (ROM) in this study. METHODS: The safety and efficacy of curcumin mouthwash 0.1% (w/v) and curcumin-nanocapsule were evaluated in ameliorating severity and pain/burning associated with OM during RT. The current randomized, placebo-controlled trial was conducted on 37 patients with head and neck cancers. Patients with grades 1 to 3 of ROM were randomized to receive one of the three interventions: curcumin mouthwash (0.1% w/v); Sinacurcumin soft gel containing 40 mg curcuminoids as nano-micelles (SinaCurcumin®40); or placebo mouthwash with a similar transparent appearance to curcumin mouthwash for 1 min three times daily during RT. Study evaluations were conducted at baseline and weekly thereafter for up to 3 weeks using the Numeric rating scale (NRS) and world health organization (WHO) scale. RESULTS: Among the 45 patients randomized, 37 (mean (SD) age of 53.36 (15.99) years; 14 [37.8%] women) completed the treatment according to the protocol. Patients treated with either oral or topical curcumin showed a significantly reduced severity and burning related to OM during the first 3 weeks after administration (P-Value < 0.001) as compared with the placebo. At study termination, more than 33% of subjects utilizing curcumin mouthwash and 15% of patients utilizing curcumin-nanocapsule remained ulcer free while all of the placebo-receiving subjects had OM. The reduction of NRS and WHO scale between curcumin groups was comparable without significant differences. CONCLUSION: Both curcumin mouthwash and nanocapsule were effective, safe, and well-tolerated in the treatment of radiation-induced OM. Higher doses of curcumin and larger sample sizes can be used for further investigation in future studies. TRIAL REGISTRATION: https://irct.ir/ IRCT20190810044500N17 (13/08/2021).

Identification of potential molecular mechanisms and candidate drugs for radiotherapy- and chemotherapy-induced mucositis.

BACKGROUND: Radiotherapy-induced oral mucositis (RIOM) and chemotherapy-induced oral mucositis (CIOM) are common complications in cancer patients, leading to negative clinical manifestations, reduced quality of life, and unsatisfactory treatment outcomes. OBJECTIVE: The present study aimed to identify potential molecular mechanisms and candidate drugs by data mining. METHODS: We obtained a preliminary list of genes associated with RIOM and CIOM. In-depth information on these genes was explored by functional and enrichment analyses. Then, the drug-gene interaction database was used to determine the interaction of the final enriched gene list with known drugs and analyze the drug candidates. RESULTS AND CONCLUSION: This study identified 21 hub genes that may play an important role in RIOM and CIOM, respectively. Through our data mining, bioinformatics survey, and candidate drug selection, TNF, IL-6, and TLR9 could play an important role in disease progression and treatment. In addition, eight candidate drugs (olokizumab, chloroquine, hydroxychloroquine, adalimumab, etanercept, golimumab, infliximab, and thalidomide) were selected by the drug-gene interaction literature search additionally, as candidates for treating RIOM and CIOM.

A pelvic mass 21 years after a Wilms tumour: late recurrence or new tumour?

INTRODUCTION: Late Wilms tumour (WT) recurrences are rare events with poorly understood pathogenesis. They could be induced by previous chemo- and radiotherapy regimens, which can also prompt a rhabdomyomatous differentiation. Prostatic embryonal rhabdomyosarcoma (PER) is an extremely rare disease in adults, with an aggressive behaviour and abysmal prognosis. Radio-induced PER have been described. CASE DESCRIPTION: We report the case of a 29 years old man, with a history of WT, diagnosed with a symptomatic prostatic mass. Blastemic elements were shown at the transrectal biopsy, suggesting the possibility of a late WT recurrence. After laparoscopic resection, an unexpected pathologic diagnosis was reached: PER. CONCLUSION: We retrace and analyse the diagnostic and therapeutic path of the case that represents a mixture of two different conditions which might be unrelated or intertwined in a causal relationship. Among the differential diagnosis of a prostatic mass, the possibility of a prostatic sarcoma should not be overlooked, in presence of blastemic elements, even in a patient with a WT history.

The Undervalued Acute Leukopenia Induced By Radiotherapy In Cervical Cancer.

BACKGROUND: Myelosuppression is common and threatening during tumor treatment. However, the effect of radiation on bone marrow activity, especially leukocyte count, has been underestimated in cervical cancer. The aim of this study was to evaluate the severity of radiotherapy- induced acute leukopenia and its relationship with intestinal toxicity. METHODS: The clinical data of 59 patients who underwent conventional radiation alone for cervical cancer were retrospectively analyzed. The patients had normal leukocyte count on admission, and the blood cell count, gross tumor volume (GTV) dose, and intestinal toxicity were evaluated. RESULTS: During radiotherapy (RT), 47 patients (79.7%) developed into leukopenia, with 38.3% mild and 61.7% moderate. The mean time for leukopenia was 9 days. Compared with leukopenianegative patients, leukopenia-positive ones had lower baseline leukocyte count, while neutrophil/ lymphocyte (NLR) and monocyte/lymphocyte (MLR) showed no significance. Logistic regression analysis indicated that excluding the factors for age, body mass index (BMI), TNM stage, surgery and GTV dose, baseline leukocyte count was an important independent predictor of leukopenia (OR=0.383). During RT, a significant reduction was found in leukocyte, neutrophil and lymphocyte count at week 2 while monocyte count after 2 weeks. Furthermore, NLR and MLR showed a significant and sustained upward trend. About 54.2% of patients had gastrointestinal symptoms. However, no significant relevance was noted between leukocyte count as well as NLR/MLR and intestinal toxicity, indicating leukopenia may not be the main factor causing and aggravating gastrointestinal reaction in cervical cancer. CONCLUSION: Our results suggest the underrated high prevalence and severity of leukopenia in cervical cancer patients receiving RT, and those with low baseline leukocyte count are more likely for leukopenia, for whom early prevention of infection may be needed during RT.

Spatial distribution of cerebral microbleeds and FLAIR hyperintensities on follow-up MRI after radiotherapy for lower grade glioma.

Background and purpose: Cerebral microbleeds (CMBs) and fluid-attenuated-inversion recovery (FLAIR) hyperintensities on brain MRI scans after radiotherapy (RT) are considered markers for microvascular damage and related cognitive changes. However, the spatial distribution using existing scoring systems as well as colocation of these imaging biomarkers remain unclear, hampering clinical interpretation. This study aims to elucidate the distribution and colocation of these markers in patients with lower grade glioma (LGG). Materials and methods: CMBs were spatially classified on retrospective 1.5 T susceptibility weighted MRI scans according to the existing Microbleed Anatomical Rating Scale (MARS) and were additionally scored for being located in hippocampus, amygdala, cortex, white matter (WM), grey matter (GM), WM/GM junction and for their spatial relation to FLAIR hyperintensities. Scoring was performed for whole, ipsilateral and contralateral cerebrum (with respect to tumour bulk). Results: Fifty-one scans were included of which 28 had at least one CMB. The majority of CMBs were localized in the lobar area and in deep and periventricular white matter (DPWM) - generally in WM. Only few CMBs were found in GM. In scans obtained up to 7 years after RT completion the majority of CMBs were not colocalized with FLAIR hyperintensities. Conclusion: CMBs and FLAIR hyperintensities appear to be separate imaging biomarkers for radiation therapy induced microvascular damage, as they are not colocalized in patients with LGG, especially not early on after completion of RT.

Case report: Triple whammy: Synchronous radiotherapy induced glioblastoma multiforme and papillary thyroid cancer following nasopharyngeal carcinoma.

Secondary malignancies following radiotherapy are well documented, with an estimated incidence of 5%. These may manifest as carcinomas, gliomas, or sarcomas within the previous radiation field. Glioblastoma multiforme following radiotherapy for nasopharyngeal carcinoma is an uncommon occurrence and carries a poor prognosis, whereas papillary thyroid carcinoma following radiotherapy is well documented, though the exact incidence is not well documented. The occurrence of synchronous radiotherapy-induced malignancy over both sites has not been described in the literature before. We describe a middle-aged gentleman diagnosed with glioblastoma multiforme and papillary thyroid carcinoma 6 years after radiotherapy for nasopharyngeal carcinoma. Though our case is the first reported case of a synchronous tumour of its nature, it is likely that such cases are under-reported. Long-term vigilance for loco-regional radiotherapy-induced secondary malignancies is a must, and the presence of a second distinct secondary malignancy must be entertained.

Ex Vivo Irradiation of Lung Cancer Stem Cells Identifies the Lowest Therapeutic Dose Needed for Tumor Growth Arrest and Mass Reduction In Vivo.

Radiotherapy represents a first-line treatment for many inoperable lung tumors. New technologies offer novel opportunities for the treatment of lung cancer with the administration of higher doses of radiation in smaller volumes. Because both therapeutic and toxic treatment effects are dose-dependent, it is important to identify a minimal dose protocol for each individual patient that maintains efficacy while decreasing toxicity. Cancer stem cells sustain tumor growth, promote metastatic dissemination, and may give rise to secondary resistance. The identification of effective protocols targeting these cells may improve disease-free survival of treated patients. In this work, we evaluated the existence of individual profiles of sensitivity to radiotherapy in patient-derived cancer stem cells (CSCs) using both in vitro and in vivo models. Both CSCs in vitro and mice implanted with CSCs were treated with radiotherapy at different dose intensities and rates. CSC response to different radiation doses greatly varied among patients. In vitro radiation sensitivity of CSCs corresponded to the therapeutic outcome in the corresponding mouse tumor model. On the other side, the dose administration rate did not affect the response. These findings suggest that in vitro evaluation of CSCs may potentially predict patients' response, thus guiding clinical decision.

Cetuximab and anemia prevention in head and neck cancer patients undergoing radiotherapy.

BACKGROUND: Epidermal growth factor receptor (EGFR) activation is associated with increased production of interleukin 6 (IL6), which is intensified by radiotherapy (RT) induced inflammatory response. Elevated IL6 levels intensifies RT-induced anemia by upregulating hepcidin causing functional iron deficiency. Cetuximab, an EGFR inhibitor, has been associated with lower rates of anemia for locally advanced head and neck squamous cell carcinoma (HNSCC). We hypothesized that concomitant cetuximab could prevent RT-induced anemia. METHODS: We queried our institutional head and neck cancers database for non-metastatic HNSCC cases that received RT with concomitant cetuximab or RT-only between 2006 and 2018. Cetuximab was administered for some high-risk cases medically unfit for platinum agents per multidisciplinary team evaluation. We only included patients who had at least one complete blood count in the 4 months preceding and after RT. We compared the prevalence of anemia (defined as hemoglobin (Hb) below 12 g/dL in females and 13 g/dL in males) and mean Hb levels at baseline and after RT. Improvement of anemia/Hb (resolution of baseline anemia and/or an increase of baseline Hb ≥1 g/dL after RT), and overall survival (OS) in relation to anemia/Hb dynamics were also compared. RESULTS: A total of 171 patients were identified equally distributed between cetuximab-plus-RT and RT-only groups. The cetuximab-plus-RT group had more locally-advanced stage, oropharyngeal and high grade tumors (p < 0.001 for all). Baseline anemia/Hb were similar, however anemia after RT conclusion was higher in the cetuximab-plus-RT vs RT-only (63.5% vs. 44.2%; p = 0.017), with a mean Hb of 11.98 g/dL vs. 12.9 g/dL; p = 0.003, for both respectively. This contributed to significantly worse anemia/Hb improvement for cetuximab-plus-RT (18.8% vs. 37.2%; p = 0.007). This effect was maintained after adjusting for other factors in multivariate analysis. The prevalence of iron, vitamin-B12 and folate deficiencies; and chronic kidney disease, was non-different. Baseline anemia was associated with worse OS (p = 0.0052) for the whole study cohort. Nevertheless, improvement of anemia/Hb was only marginally associated with better OS (p = 0.068). CONCLUSIONS: In contrast to previous studies, cetuximab was not associated with lower rates of anemia after RT for nonmetastatic HNSCC patients compared to RT-alone. Dedicated prospective studies are needed to elucidate the effect of cetuximab on RT-induced anemia.

Diagnostic Framework of Pelvic Massive Necrosis with Peritonitis following Chemoradiation for Locally Advanced Cervical Cancer: When Is the Surgery Not Demandable? A Case Report and Literature Review.

Concurrent platinum-based chemoradiation (CCRT) is the established treatment for locally advanced cervical cancer and has an acceptable toxicity. Radiation-induced necrosis of the uterus and pelvic tissue is a rare and usually late potential complication. Limited data are available about its management. Here, we describe a case of a patient affected by a locally advanced cervical cancer (stage IVA) who received CCRT, obtaining a partial response with persistence of bladder and rectal infiltration. Unfortunately, after the first brachytherapy dose, the patient developed a worsening clinical picture with fever and altered laboratory data indicative of sepsis; the computed tomography revealed a massive necrosis of the uterus with pelvic abscess and peritonitis. We performed a laparoscopic emergency surgery with removal of the necrotic tissue, supracervical hysterectomy, bilateral-oophorectomy, and abscess drainage. Thereafter, once the severe inflammatory condition was resolved, the patient underwent pelvic exenteration with palliative/curative intent. The postoperative PET/CT was negative for residual disease. However, the patient needed further hospitalization for re-occurrence of peritonitis with multiple abscesses. A careful diagnosis is crucial in locally advanced cervical cancer patients who, after CCRT, present persistent pain and problematic findings at imaging and laboratory parameters. In these cases, radiation-induced necrosis of the pelvis should be suspected. This case helps to clarify the central role of surgery, especially when actinic necrosis leads to complications such as abscess, fistulae, and extensive tissue destruction that cannot be conservatively medically handled. Laparoscopy represents an ideal approach to realizing the correct diagnosis, as well as enabling the performance of important therapeutic surgical procedures.

Quantitative Analysis of Radiation-Associated Parenchymal Lung Change.

We present a novel classification system of the parenchymal features of radiation-induced lung damage (RILD). We developed a deep learning network to automate the delineation of five classes of parenchymal textures. We quantify the volumetric change in classes after radiotherapy in order to allow detailed, quantitative descriptions of the evolution of lung parenchyma up to 24 months after RT, and correlate these with radiotherapy dose and respiratory outcomes. Diagnostic CTs were available pre-RT, and at 3, 6, 12 and 24 months post-RT, for 46 subjects enrolled in a clinical trial of chemoradiotherapy for non-small cell lung cancer. All 230 CT scans were segmented using our network. The five parenchymal classes showed distinct temporal patterns. Moderate correlation was seen between change in tissue class volume and clinical and dosimetric parameters, e.g., the Pearson correlation coefficient was ≤0.49 between V30 and change in Class 2, and was 0.39 between change in Class 1 and decline in FVC. The effect of the local dose on tissue class revealed a strong dose-dependent relationship. Respiratory function measured by spirometry and MRC dyspnoea scores after radiotherapy correlated with the measured radiological RILD. We demonstrate the potential of using our approach to analyse and understand the morphological and functional evolution of RILD in greater detail than previously possible.

The G to A transformation of rs4702 polymorphism in 3'UTR of FURIN reduced the risk of radiotherapy-induced cognitive impairment in glioma patients.

The G allele of rs4702 polymorphism has been reported to reduce the production of mature BDNF and FURIN, both of which were closely associated with cognitive functions. Real-time PCR, ELISA and luciferase assay were performed to explore the interactions between miR-338-3p, FURIN and BDNF. T-RFLP was used to assess the intestinal flora in the stool samples of glioma patients after radiotherapy. We grouped the 106 glioma patients recruited according to the rs4702 polymorphism. The results showed no obvious correlation between rs4702 polymorphism and the expression of miR-338-3p. However, rs4702-A was associated with increased expression of FURIN and BDNF in the serum and PBMC of glioma patients after radiotherapy. Besides, the study found that rs4702-A was remarkably associated with increased enterotype I and decreased enterotype III in the stool of glioma patients after radiotherapy. Rs4702-A was also proved to be closely associated with increased MMSE, role functioning and social functioning at three months after radiotherapy. Furthermore, miR-338-3p repressed the expression of FURIN-G. Compared with G allele, the presence of A allele of rs4702 polymorphism in FURIN could obstruct the suppressive effect of miR-338-3p upon the expression of FURIN and BDNF in intestinal flora. Therefore, the carriers of A allele will be challenged with less risk of radiotherapy-induced cognitive impairment.