Combined Chemoradiotherapy Research Articles

Highlights of the ASCO and ESMO annual meetings 2022: radiotherapy of head and neck cancer

At the 2022 annual meetings of the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO), several studies on radiation therapy for head and neck squamous cell carcinoma (HNSCC) were presented. Among the main topics were new concepts for treatment de-escalation with the goal of reducing side effects. Radiotherapy alone for nasopharyngeal carcinoma with an intermediate-risk profile was found to be noninferior to chemoradiotherapy with cisplatin while improving tolerability. In the phaseII DIREKHT trial for adjuvant radiotherapy, individualized deintensification concepts of radiation dose or volume were implemented. Overall, this treatment resulted in excellent levels of locoregional control with aminimal side effects profile. In subgroup analysis, however, an increased locoregional recurrence rate was observed for tumors of the oral cavity. In 2022, as in the previous year, there was acontinued focus on the role of immune checkpoint inhibitors in combination with platinum-based chemoradiotherapy in the first-line treatment of locally advanced HNSCC. In the HNSCC-15-132 trial, sequential application of the PD‑1 inhibitor pembrolizumab to chemoradiotherapy was not significantly, but numerically superior to concomitant application. The phaseIII KEYNOTE-412 trial evaluated the efficacy of concomitant and sequential additive pembrolizumab therapy compared to additive placebo in 804patients with locally advanced HNSCC. The observed benefit in terms of event-free survival in the pembrolizumab group marginally missed statistical significance, probably due to the particular study design. In addition, new 5‑year overall survival data from the phaseII trial of chemoradiotherapy in combination with the inhibitor of apoptosis proteins (IAP) antagonist xevinapant versus placebo were presented. The xevinapant group continued to demonstrate asignificant survival advantage and asustained response to treatment.

Effectiveness of zinc supplementation on the incidence of oral mucositis during chemotherapy and radiation: A meta‑analysis.

Oral mucositis (OM) is a commonly observed and debilitating side effect of chemotherapy and radiation therapy in patients with cancer, especially head and neck cancer. Although there is no proven therapy for the prevention and treatment of OM, zinc supplementation effectively decreases the incidence of OM. This paper provides a current and comprehensive meta-analysis of the efficacy of zinc compared with placebo/control in OM. A systematic literature review was conducted using MEDLINE and Central databases for randomized control trials (RCTs) comparing zinc supplementation (oral or rinse) with placebo/control in patients with various types of cancer undergoing chemotherapy, radiation therapy or combined chemo-radiation. The outcome was OM incidence, independent of the severity. A random-effects model was used to calculate the pooled risk ratio and subgroup analyses were performed. A total of 12 RCTs were included, containing information from 783 patients. A decrease in OM incidence was observed overall when all cancer therapies were considered. However, subgroup analyses showed that zinc did not significantly decrease the incidence of OM when studies were stratified by cancer therapy or scale/criteria used to assess OM. The results of the meta-analysis support the use of zinc supplementation in decreasing OM incidence in patients with cancer receiving chemotherapy or radiation therapy. However, the high heterogeneity between studies and the small number of studies are limitations of the meta-analysis.

XPF-ERCC1 Blocker Improves the Therapeutic Efficacy of 5-FU- and Oxaliplatin-Based Chemoradiotherapy in Colorectal Cancer.

5-FU-based chemoradiotherapy (CRT) and oxaliplatin-based CRT are commonly used therapies for advanced colorectal cancer (CRC). However, patients with a high expression of ERCC1 have a worse prognosis than those with a low expression. In this study, we investigated the effect of XPF-ERCC1 blockers on chemotherapy and 5-FU-based CRT and oxaliplatin (OXA)-based CRT in colorectal cancer cell lines. We investigated the half-maximal inhibitory concentration (IC50) of 5-FU, OXA, XPF-ERCC1 blocker, and XPF-ERCC1 blocker, and 5-FU or OXA combined and analyzed the effect of XPF-ERCC1 blocker on 5-FU-based CRT and oxaliplatin-based CRT. Furthermore, the expression of XPF and γ-H2AX in colorectal cells was analyzed. In animal models, we combined the XPF-ERCC1 blocker with 5-FU and OXA to investigate the effects of RC and finally combined the XPF-ERCC1 blocker with 5-FU- and oxaliplatin-based CRT. In the IC50 analysis of each compound, the cytotoxicity of the XPF-ERCC1 blocker was lower than that of 5-FU and OXA. In addition, the XPF-ERCC1 blocker combined with 5-FU or OXA enhanced the cytotoxicity of the chemotherapy drugs in colorectal cells. Furthermore, the XPF-ERCC1 blocker also increased the cytotoxicity of 5-FU-based CRT and OXA -based CRT by inhibiting the XPF product DNA locus. In vivo, the XPF-ERCC1 blocker was confirmed to enhance the therapeutic efficacy of 5-FU, OXA, 5-FU-based CRT, and OXA CRT. These findings show that XPF-ERCC1 blockers not only increase the toxicity of chemotherapy drugs but also increase the efficacy of combined chemoradiotherapy. In the future, the XPF-ERCC1 blocker may be used to improve the efficacy of 5-FU- and oxaliplatin-based CRT.

Advanced cervical stump cancer after laparoscopic subtotal hysterectomy: a case report of imaging, laparoscopic staging and treatment approach

BackgroundAdvanced cancer of the cervical stump, occurring years after a laparoscopic supracervical hysterectomy (LASH), is a rare but serious clinical condition. Many patients who undergo a LASH are unaware of this possible complication. Upon diagnosis of advanced cervical stump cancer, a holistic approach including imaging, laparoscopic surgery and multimodal oncological therapy is required.Case presentationA 58-year-old patient presented to our department with the suspicion of advanced cervical stump cancer eight years after LASH. She reported pelvic pain, irregular vaginal bleedings and irregular discharge. Gynaecological examination revealed a locally advanced tumor of the uterine cervix with suspicion of infiltration of the left parametria and bladder. After thorough diagnostic imaging and laparoscopic staging, the tumor stage was determined as FIGO IIIB and the patient was treated with combined radiochemotherapy. The patient presented with tumor recurrence 5 months after the completion of therapy and she is currently being treated with multichemotherapy and immunotherapy regimens as palliative treatment.ConclusionPatients should be made aware about the risk of cervical stump carcinoma after LASH and the necessity for regular screening. Cervical cancer after LASH is often diagnosed at advanced stages and the treatment requires an interdisciplinary approach.

Intratumoral injection of oncolytic virus (H101) in combination with concurrent chemoradiotherapy for locally advanced cervical cancer

ObjectivesTo evaluate the efficacy of primary tumor bulk reduction and the safety of concurrent chemoradiotherapy in combination with H101, a type of oncolytic virus, for the treatment of locally advanced...

Anti-Cancer and Radio-Sensitizing Properties of New Bimetallic (N-Heterocyclic Carbene)-Amine-Pt(II) Complexes.

Bioactive NHC-transition metal complexes have shown promise as anti-cancer agents, but their potential use as radiosensitizers has been neglected so far. We disclose here a new series of bimetallic platinum(II) complexes displaying NHC-type bridging ligands, (bis-NHC)[trans-Pt(RNH2)I2]2, that have been synthesized via a simple, two-step procedure. They display cytotoxicity in the micromolar range on cancerous cell lines, accumulate in cells, and bind to genomic DNA, by inducing DNA damages. Notably, these bimetallic complexes demonstrate significant radiosensitizing effects on both ovarian cells A2780 and nonsmall lung carcinoma cells H1299. Further investigations revealed that bimetallic species make irradiation-induced DNA damages more persistent by inhibiting repair mechanisms. Indeed, a higher and persistent accumulation of both γ-H2AX and 53BP1 foci post-irradiation was detected, in the presence of the NHC-Pt complexes. Overall, we provide the first in vitro evidence for the radiosensitizing properties of NHC-platinum complexes, which suggests their potential use in combined chemo-radio therapy protocols.

Endocrine disorders after combined chemoradiotherapy in Hodgkin Lymphoma survivors

Hodgkin's lymphoma (HL) is one of the most common malignant lymphoproliferative diseases. Chemotherapy and radiotherapy used in the treatment of LH induce a number of toxic effects leading to dysfunction of endocrine system. Hormonal disorders in HL and their relationships with the therapy used remain to be clarified. To assess disorders of the endocrine function of thyroid, parathyroid glands and gonads in HL survivors. Screening of endocrine dysfunction of the thyroid, parathyroid glands and gonads was performed in 160 adult patients with HL, 55 men and 105 women, at remission stage induced by chemotherapy or chemoradiotherapy. Forty healthy subjects, matched by age, were acted as control. The levels of TSH, T3, free T4, PTH, FSH, LH, free testosterone, dehydroepiandrosterone sulfate (DHEA-S), and sex-hormone binding globulin (SHBG) were measured in blood serum by ELISA. Bone mineral density (BMD) was assessed by DEXA. Hypothyroidism (25%), hyperparathyroidism (15.6%) and hypogonadism (29% of men and 25.3% of women) were the most prevalent endocrine disorders in LH survivors. Hypothyroidism was significantly more common in patients after chemoradiotherapy than in those who received only chemotherapy (χ2=9.4, р=0.002). In patients with hyperparathyroidism, there were negative correlations between PTH levels and BMD in the lumbar spine (r=-0.74, p=0.00002) and in the femoral neck (r=-0.66, p=0.0003). Men with HL demonstrated lower free testosterone concentrations when compared to control (p=0.04); LH and FSH levels were elevated (p=0.0004 and p=0.04, respectively). In men with HL the levels of DHEA-S were reduced (p=0.0009). The increased SHBG concentrations were revealed in 13 (23.6%) men. Women of reproductive age with HL had higher levels of LH in the luteal phase (p=0.05) and FSH in the follicular phase (p=0.02) than controls. The data indicate a high prevalence of the dysfunctions of thyroid, parathyroid glands, and gonads in HL survivors. Screening for endocrine disorders in these patients is highly recommended.

Multi-stimuli-responsive starch/MnO2 microparticles hydrogel for synergistic chemoradiotherapy of breast cancer

Microparticles hydrogel sensitive to reduction, pH and radiation composed of starch (St) and MnO2 NPs were synthesized, and loaded with Dox for in vitro treatment of MCF-7 cells. LE and EE values were obtained as 3.12 and 93.4%, respectively. In vitro drug release study revealed pH- and reduction-responsiveness drug release behavior of the DDS. The intracellular uptake of the St/MnO2 microparticles was verified through FITC dye conjugation. The St-MnO2/Dox microparticles exhibited higher anticancer activity than free Dox after 48 h as verified by MTT and DAPI staining assays. As results, combined chemoradiotherapy approach exhibited synergistic outcomes than chemotherapy alone.

Pneumonitis with combined immune checkpoint inhibitors and chemoradiotherapy in locally advanced non-small-cell lung cancer: a systematic review and meta-analysis.

Aims: This study systematically evaluated cases of pneumonitis following combined immune checkpoint inhibitors (ICI) and chemoradiotherapy (CRT) for locally advanced non-small-cell lung cancer (LA-NSCLC). Methods: Studies from Embase, PubMed and the Cochrane Library on patients with LA-NSCLC who received CRT and ICIs were reviewed. The primary outcomes were rates of all-grade, grade 3-5 and grade 5 pneumonitis. Results: Overall, 35 studies involving 5000 patients were enrolled. The pooled rates of all-grade, grade 3-5 and grade 5 pneumonitis were 33.0% (95% CI: 23.5-42.6), 6.1% (95% CI: 4.7-7.4) and 0.8% (95% CI: 0.3-1.2), respectively, with 7.6% of patients discontinuing ICIs because of pneumonitis. Conclusion: The incidence rates of pneumonitis following combined CRT and ICIs for LA-NSCLC were acceptable. However, the pulmonary toxicity of concurrent CRT and nivolumab plus ipilimumab should be noted.

Abstract #1384628: An Incidental Thyroid Lesion on FDG-PET Scan in a Patient with Long History of Hypothyroidism and Radiation Exposure

An 81-year-old woman with history of lung cancer and hypothyroidism with an incidental thyroid lesion on (FDG)-positron emission tomography (PET) scan is subsequently diagnosed with primary thyroid lymphoma (PTL) using flow cytometry. An 81-year-old woman with a history of lung cancer and hypothyroidism presented to the endocrinology office for evaluation of a thyroid lesion. Primary hypothyroidism was diagnosed 30 years prior to presentation and was controlled with levothyroxine 88 mcg daily. Lung cancer was diagnosed 8 years prior, and treated with radiation therapy. Patient had an FDG-PET scan obtained for the evaluation of lung nodules, and a hypermetabolic focus was noted in the left thyroid region with a max SUV of 18. On thyroid ultrasound, the left thyroid lobe appeared heterogenous with solid nodular areas. The physical exam revealed a smooth but firm thyroid gland, without cervical lymphadenopathy. Laboratory workup showed thyroid stimulating hormone and free thyroxine in the normal range. Microsomal antibody was 4.2 IU/mL (< 5.6 IU/mL), and thyroglobulin antibody was 356.4 IU/mL (< 14.4 IU/mL). Fine needle aspiration (FNA) biopsy showed a polymorphous lymphoid sample. Given the high SUV on PET-scan and longstanding history of Hashimoto’s thyroiditis, repeat FNA biopsy with flow cytometry was subsequently performed and showed a lymphoid population consistent with a non-Hodgkin lymphoma (NHL). The patient was referred to oncology and diagnosed with indolent NHL. Further staging revealed interval growth in lung nodules, with biopsy showing recurrence of adenocarcinoma, but no other metastatic disease. The patient underwent radiation therapy for both her lung adenocarcinoma and primary thyroid lymphoma (PTL). Primary thyroid lymphoma accounts for less than 5% of thyroid cancers. It presents with a female predominance in the 7th decade of life, with Hashimoto’s thyroiditis as the main risk factor. Patients may present with an enlarging neck mass, with or without compressive symptoms, and cervical lymphadenopathy. Diagnosis of PTL can be made through FNA biopsy, core biopsy, or open surgical biopsy. It is important to note that because these lesions have few pathognomonic features, diagnosis with FNA biopsy alone can be difficult, and sensitivity is increased to 97% with the use of flow cytometry, as was demonstrated in our case. Treatment is with radiation therapy or combined chemoradiotherapy. Surgery has a role limited to the management of airway compromise, as surgical resection has not proven to improve overall survival. This case highlights the utility of including flow cytometry with FNA sample when diagnosing PTL.

Fibrous dysplasia mimicking skeletal involvement in Lymphoma.

We present the case of a 19-year-old male with nodular sclerosing classical Hodgkin lymphoma, who had an incidental finding of fibrous dysplasia of the bone. This caused 18-F-fluorodeoxyglucose (18-F-FDG) avidity on positron emission tomography-computed tomography (PET-CT) scan leading to incorrect initial staging. This patient presented with a 4-month history of enlarging cervical lymph nodes, without B symptoms. He had no prior medical history. His initial diagnostic 18-F-FDG PET-CT demonstrated moderately avid left cervical and superior mediastinal lymphadenopathy and two partially sclerotic, partially lytic bone lesions. These were moderately avid, one in the proximal right humerus (SUV 6.1) and the second in the posterior distal humerus (SUV 8.1). There was no other avid lymphadenopathy (see Figure 1). He had a magnetic resonance imaging (MRI) scan and an orthopaedic opinion was sought; the lesions were felt likely to be skeletal involvement of his Hodgkin lymphoma. Therefore, his staging was 4A, with an international prognostic score of 2, and treatment was commenced following a RATHL approach starting with ABVD chemotherapy. The interim PET-CT scan following cycle 2 of ABVD demonstrated a complete metabolic response within the cervical and mediastinal lymphadenopathy, but persistent avidity within the right humeral shaft lesions which were essentially unchanged in size with a mild reduction in 18-F-FDG avidity (see Figure 2). He did report some aching in the right arm. This discrepant radiological response prompted further investigation. The bone lesions were evaluated with a CT and MRI scan, and his case was discussed again with the orthopaedic team who at that point felt the radiological appearances were suggestive of fibrous dysplasia. He had a biopsy of the bone lesion and histological examination confirmed the diagnosis of fibrous dysplasia with no evidence of Hodgkin lymphoma or other primary bone malignancy. The patient's staging was therefore amended to stage 2A early favourable (ESR 4 mm/h at diagnosis), and treatment was changed to combined modality chemo-radiotherapy. He had already completed 2 cycles of ABVD and so proceeded to receive 20 Gy in 10 fractions of consolidation radiotherapy. His end-of-treatment PET-CT scan is awaited but clinically he remains in complete remission. He will require surveillance imaging of the bony lesions. Fibrous dysplasia of the bone (FD) is an uncommon genetic disorder causing benign fibroosseous bone lesions. It is diagnosed predominantly in children and young adults. It has a wide spectrum of presentations but is often asymptomatic and can be found incidentally. Malignant transformation can rarely occur. Radiological features can vary from classical ground glass lesions to cystic or sclerotic lesions. FD lesions can show a large variability in 18-F-FDG uptake on PET-CT, and avidity in FD may change over time. There are several other case reports of FD mimicking skeletal involvement in lymphoma. In conclusion, discrepant responses to treatment should be further investigated. Careful interpretation of 18-F-FDG avid bone lesions is required to avoid misdiagnosis or overtreatment. FD should be considered within the differential diagnosis, especially in younger patients. Orla Gildea: conception, literature review and writing—original draft preparation Claire Burney: supervision and writing—review and editing Julian Kabala: resources, visualisation The authors declare no conflict of interest. Self. N/A. Uploaded. N/A. Not applicable to this article as no new data were created or analysed.

ASTRO Radiation Therapy Summary of the ASCO Guideline on Management of Stage III Non-Small Cell Lung Cancer

To develop a radiation therapy summary of recommendations on the management of locally advanced non-small cell lung cancer (NSCLC) based on the Management of Stage III Non-Small Cell Lung Cancer: American Society of Clinical Oncology Guideline, which was endorsed by the American Society for Radiation Oncology (ASTRO). The American Society of Clinical Oncology, ASTRO, and the American College of Chest Physicians convened a multidisciplinary panel to develop a guideline based on a systematic review of the literature and a formal consensus process, that has been separately published. A new panel consisting of radiation oncologists from the original guideline as well as additional ASTRO members was formed to provide further guidance to the radiation oncology community. A total of 127 articles met the eligibility criteria to answer 5 clinical questions. This summary focuses on the 3 radiation therapy questions (neoadjuvant, adjuvant, and unresectable settings). Radiation-specific recommendations are summarized with additional relevant commentary on specific questions regarding the management of preoperative radiation, postoperative radiation, and combined chemoradiation. Patients with stage III NSCLC who are planned for surgical resection, should receive either neoadjuvant chemotherapy or chemoradiation. The addition of neoadjuvant treatment is particularly important in patients planned for surgery in the N2 or superior sulcus settings. Postoperatively, patients who did not receive neoadjuvant chemotherapy should be offered adjuvant chemotherapy. The use of postoperative radiation for completely resected N2 disease is not routinely recommended. Unresectable patients with stage III NSCLC should ideally be managed with combined concurrent chemoradiation using a platinum-based doublet with a standard radiation dose of 60 Gy followed by consolidation durvalumab in patients without progression after initial therapy. Patients who cannot tolerate a concurrent chemoradiation approach can be managed either by sequential chemotherapy followed by radiation or by dose-escalated or hypofractionated radiation alone.

Association Between Lymphopenia and Survival Outcomes in Esophageal Carcinoma Patients Receiving Combined Immunotherapy and Chemoradiotherapy.

To investigate the association between absolute lymphocyte count (ALC) nadir and survival outcomes in esophageal squamous cell carcinoma (ESCC) patients who received definitive chemoradiotherapy (CRT) combined with anti-PD-1 immunotherapy, as well as to explore clinical characteristics and dosimetric parameters that affect ALC nadir during CRT. Patients with ESCC (n = 602) who underwent definitive CRT were analyzed, of whom 166 received combined anti-PD-1 immunotherapy and CRT. Changes in ALC and survival were compared between patients with and without immunotherapy. Propensity score matching (PSM) was performed to minimize the effects of confounding factors. Low ALC was defined as nadir of <0.33 × 103 cells/μL during CRT (top tertile). Univariate and multivariate logistic regression were used to identify predictors of low ALC nadir. Patients with immunotherapy had significantly higher ALC in the first 3 weeks during CRT and higher ALC nadir than those without. Overall survival was more favorable in patients with immunotherapy both before and after PSM. After a median follow-up of 12.1 months, patients with low ALC during CRT had a worse progression-free survival (PFS) (P = .026). In multivariate analysis, low ALC remained a significant prognostic factor for PFS. Planning target volume (PTV) and heart V5 were revealed to be independent predictors of low ALC. The addition of anti-PD-1 immunotherapy to definitive CRT could mitigate the decline of ALC during radiotherapy and might prolong survival. Low ALC nadir was correlated to worse PFS, larger PTV, and higher heart V5 in patients receiving combined immunotherapy and CRT.

Diagnostics, treatment and aftercare of anal cancer

Despite the increasing incidence, anal cancer is still a rare gastrointestinal tumor, so that due to the broadness of the primary care there is often little experience in the care of affected patients. Squamous cell cancer (SCC) constitutes more than 90% of all anal cancers and is nearly always associated with an infection by the human papillomavirus. This article concentrates on SCC of the anal canal and anal margin. The focus is on the primary diagnostics, surgical treatment, response assessment and aftercare. Treatment is carried out according to the decision of the interdisciplinary tumor board, independent of the tumor location and stage. Anal margin cancer in stage I (and IIa) can be successfully treated by an R0 excision. Combined chemoradiotherapy as the standard treatment in stages II and III is briefly summarized. The article is essentially based on the new German S3 guidelines on anal cancer.

Evaluation of the Possibilities of Magnetic Resonance Imaging in Monitoring the Treatment of Locally Advanced Cervical Cancer

Background: Cervical cancer occupies one of theleading places in cancer incidence in women. Preservation of residual tumor in patients with cervical cancer after completion of combined chemoradiotherapy is a prognostically unfavorable factor. Detection of an early tumor response to chemoradiation therapy is of great importance for choosing the optimal treatment tactics.Purpose: To study the possibilities of MRI in assessing the effectiveness of detecting an early tumor response in patients with locally advanced cervical cancer after combined chemoradiotherapy.Material and methods: The results of magnetic resonance imaging of the pelvic organs, data of laboratory, cytological and postoperative histological studies of 174 patients with locally advanced cervical cancer were analyzed and compared.MRI of the pelvic organs was performed before the start of treatment to assess the extent of the process (primary study) and 6 weeks after the completion of combined chemoradiotherapy to assess the effectiveness of the treatment and detect residual tumor (control study).Conclusion: Magnetic resonance imaging of the pelvic organs using a standard research protocol, including obtaining diffusion-weighted images and dynamic contrast studies, is a highly informative method for staging locally advanced cervical cancer and assessing the tumor response to treatment.

LAT1 is associated with poor prognosis and radioresistance in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) has been identified as the sixth most common disease in the world, and its prognosis remains poor. The basic treatment of HNSCC includes a combination of chemoradiation and surgery. With the advent of immune checkpoint inhibitors, the prognosis has improved; however, the efficacy of checkpoint inhibitors is limited. L-type amino acid transporter 1 (LAT1), an amino acid transporter, is highly expressed in a cancer-specific manner. However, to the best of our knowledge, LAT1 expression in HNSCC has not been determined. Therefore, the present study aimed to examine the role of LAT1 expression in HNSCC. A total of three HNSCC cell lines (Sa3, HSC2 and HSC4) were used to investigate the characteristics of LAT1-positive cells, including their ability to form spheroids, and their invasion and migration. The present study also examined LAT1 by immunostaining of biopsy specimens from 174 patients diagnosed, treated and followed-up at Akita University (Akita, Japan) between January 2010 and December 2019, and overall survival, progression-free survival and multivariate analyses were performed. The results demonstrated that LAT1-positive cells in HNSCC were an independent prognostic factor for overall survival and progression-free survival, and were resistant to chemoradiation. Therefore, JPH203, a LAT1 inhibitor, may be effective in treating chemoradiotherapy-resistant HNSCC and may improve the prognosis of patients with HNSCC.

Systematic in vitro analysis of therapy resistance in glioblastoma cell lines by integration of clonogenic survival data with multi-level molecular data

Despite intensive basic scientific, translational, and clinical efforts in the last decades, glioblastoma remains a devastating disease with a highly dismal prognosis. Apart from the implementation of temozolomide into the clinical routine, novel treatment approaches have largely failed, emphasizing the need for systematic examination of glioblastoma therapy resistance in order to identify major drivers and thus, potential vulnerabilities for therapeutic intervention. Recently, we provided proof-of-concept for the systematic identification of combined modality radiochemotherapy treatment vulnerabilities via integration of clonogenic survival data upon radio(chemo)therapy with low-density transcriptomic profiling data in a panel of established human glioblastoma cell lines. Here, we expand this approach to multiple molecular levels, including genomic copy number, spectral karyotyping, DNA methylation, and transcriptome data. Correlation of transcriptome data with inherent therapy resistance on the single gene level yielded several candidates that were so far underappreciated in this context and for which clinically approved drugs are readily available, such as the androgen receptor (AR). Gene set enrichment analyses confirmed these results, and identified additional gene sets, including reactive oxygen species detoxification, mammalian target of rapamycin complex 1 (MTORC1) signaling, and ferroptosis/autophagy-related regulatory circuits to be associated with inherent therapy resistance in glioblastoma cells. To identify pharmacologically accessible genes within those gene sets, leading edge analyses were performed yielding candidates with functions in thioredoxin/peroxiredoxin metabolism, glutathione synthesis, chaperoning of proteins, prolyl hydroxylation, proteasome function, and DNA synthesis/repair. Our study thus confirms previously nominated targets for mechanism-based multi-modal glioblastoma therapy, provides proof-of-concept for this workflow of multi-level data integration, and identifies novel candidates for which pharmacological inhibitors are readily available and whose targeting in combination with radio(chemo)therapy deserves further examination. In addition, our study also reveals that the presented workflow requires mRNA expression data, rather than genomic copy number or DNA methylation data, since no stringent correlation between these data levels could be observed. Finally, the data sets generated in the present study, including functional and multi-level molecular data of commonly used glioblastoma cell lines, represent a valuable toolbox for other researchers in the field of glioblastoma therapy resistance.

Primary Bone Lymphoma: A Review of the Literature with Emphasis on Histopathology and Histogenesis.

Primary bone lymphoma (PBL) is a rare neoplasm of malignant lymphoid cells presenting with one or more bone lesions without nodal or other extranodal involvement. It accounts for approximately 1% of all lymphomas and 7% of malignant primary bone tumors. Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) represents the predominant histological type and constitutes over 80% of all cases. PBL may occur at all ages with a typical diagnosis age of 45-60 years and a slight male predominance. Local bone pain, soft tissue edema, palpable mass and pathological fracture are the most common clinical features. Diagnosis of the disease, which is frequently delayed due to its non-specific clinical presentation, is based on the combination of clinical examination and imaging studies and confirmed by combined histopathological and immunohistochemical examination. PBL can develop in any part of the skeleton, although it occurs most commonly in the femur, humerus, tibia, spine and pelvis. The imaging appearance of PBL is highly variable and unspecific. In terms of the cell-of-origin, most cases of primary bone DLBCL (PB-DLBCL), NOS belong to the germinal center B-cell-like subtype and specifically originate from germinal center centrocytes. PB-DLBCL, NOS has been considered a distinct clinical entity based on its particular prognosis, histogenesis, gene expression and mutational profile and miRNA signature. PBL carries a favorable prognosis, especially when treated with combined chemoradiotherapy.

Sodium deoxyribonucleate effects on the status of cervical cancer patients after radiotherapy

Background. Apart from surgery and medications, radiation therapy is one of the main treatment methods for malignant tumors of the cervix. However, its use is associated with high incidence of urological complications. In addition, the need for long-term treatment, reduced level of patients’ quality of life promote the necessity to minimize the frequency of urological complications and justify search and study of the most adequate methods of their prevention.Aim. To evaluate the effect of radioprotector sodium deoxyribonucleate on clinical characteristics and quality of life of patients with cervical cancer after radiation treatment.Materials and methods. 80 patients with cervical cancer treated in A.I. Kryzhanovsky Krasnoyarsk Regional Clinical Oncology Dispensary. Patients received chemoand radiotherapy with the 3D conformal radiotherapy method in combination with intracavity gamma therapy sources of high dose with subsequent application of radioprotector and without it.Results. On the 3rd visit it was found that in patients with cervical cancer using a radioprotector, reduced red blood cells and flat epithelium cells content in the urine sediment, it may be due to the reparative and cytoprotective sodium deoxyribonucleate properties. In the assessment of the life quality after combined therapy completion with radioprotector, 60 % of patients’ responses to the health assessment questions of the last week differed from the comparison group. Undesirable phenomena associated with sodium deoxyribonucleate therapy not observed in cervical cancer patients during radiotherapy and subsequent observation period.Conclusion. Conformal external beam radiation therapy in combination with long-term intramuscular administration of a radioprotector has advantages compared to 3D conformal radiation therapy. This method reduces the severity of post-radiation side effects, increases time to development of hematological toxicity in the context of combination chemoradiotherapy, and reduces urothelial damage caused by chemoradiotherapy.

Real World Analysis of Quality of Life and Toxicity in Cancer Patients Treated with Hyperthermia Combined with Radio(chemo)therapy.

Hyperthermia (HT) in combination with radio(chemo)therapy (RCT) is a well-established cancer treatment strategy. This report analyses the quality of life (QoL), toxicity and survival outcomes in patients with different tumor entities who received HT in combination with RCT. The primary endpoint of this study was the assessment of QoL scale items 3 and 12 months after treatment in patients who were treated with palliative intent and curative intent, respectively. The secondary endpoints of this study were acute toxicities, 1-year overall survival (OS), and local progression-free survival (LPFS). Patients treated with curative intent experienced significant improvement in emotional functioning (EF), social functioning (SF), financial difficulties (FI) and insomnia (SL) 12 months after treatment. Patients had significantly improved FI and pain (PA) three months after palliative treatment. Acute toxicity of grade 3 or more was 26% during treatment and 4% after three months. The 1-year OS rates were 90% (95% CI: 79-96%) and 44% (95% CI: 31-59%) for patients treated with curative and palliative RCT combined with HT, respectively. Moreover, the 1-year LPFS rates were 94% (95% CI: 84-98%) for patients treated with curative intent and 64% (95% CI: 50-77%) for palliative patients. In summary, combined RCT and HT stabilized or improved QoL scale items for both curative and palliative indications.