IFN-Type-I Response and Systemic Immunity in Rectal Adenocarcinoma Patients Treated with Conventional or Hypofractionated Neoadjuvant Radiotherapy.

The IFN-type-I pathway is involved in radiotherapy (RT)-mediated immune responses. Large RT fractions have been suggested to potently induce this pathway. Neoadjuvant hypofractionated short-course (scRT) and conventional long-course (lcRT) RT applied for the treatment of locally advanced rectal adenocarcinoma patients provides a unique model to address the immuno-stimulatory properties of RT on a systemic level. We prospectively analyzed the IFNß plasma levels and lymphocyte counts (LCs) of rectal adenocarcinoma patients before and after treatment with scRT (n = 22) and lcRT (n = 40). Flow cytometry was conducted to assess the effects on lymphocytic subpopulations in a subset of 20 patients. A statistically significant increase in the post-RT IFNß plasma levels was noted in patients undergoing scRT (p = 0.004). Improved pathological tumor regression was associated with elevated post-RT IFNß levels (p = 0.003). Although all patients experienced substantial lymphopenia after treatment, the post-RT LC of patients treated with scRT were significantly higher compared to lcRT (p = 0.001). Patients undergoing scRT displayed significantly lower percentages of regulatory CD4+/CD25+ T-cells after therapy (p = 0.02). scRT enables effective stimulation of the IFN-type-I pathway on a systemic level and confers decreased lymphocytic cytotoxicity and limited regulatory T-cell activation compared to lcRT, supporting its increasing role in immuno-RT trials.

Comprehensive 3DCRT Hypofractionated Radiotherapy Schedule for Localized Prostate Adenocarcinoma in the Era of IMRT: Dosimetric and Endoscopic Analysis.

Background: Moderate hypofractionated radiotherapy (MHRT) has emerged as the preferred treatment modality for localized prostate cancer based on randomized controlled studies regarding efficacy and toxicity using contemporary radiotherapy techniques. In the setting of MHRT, available data on dosimetric parameters and late rectal toxicity are limited. Aim: To present the effects of MHRT on late rectal toxicity while conducting an extensive dosimetric analysis in conjunction with rectoscopy results. Methods: This is a prospective study including patients with intermediate-risk prostate adenocarcinoma. All patients were treated with MHRT 44 Gy in 16 fractions to the seminal vesicles and to the prostate, followed by a sequential boost to the prostate alone of 16.5 Gy in 6 fractions delivered with three-dimensional conformal radiation therapy (3DCRT). Acute and late toxicity were assessed. Endoscopy was performed at baseline, every 3 months post-therapy for the first year, and every 6 months for the year after. The Vienna Rectoscopy Score (VRS) was used to assess rectal mucosal injury related to radiotherapy. Dosimetric analysis for the rectum, rectal wall, and its subsegments (upper, mid, and low 1/3) was performed. Results: Between September 2015 and December 2019, 20 patients enrolled. Grade 1 late gastrointestinal toxicity occurred in 10% of the patients, whereas 5% had a grade ≥2. Twelve months post radiotherapy: 4 (20%) patients had VRS 1; 2 (10%) patients had VRS 2; 1(5%) patient had VRS 3. 24 months post radiotherapy, VRS 1 was observed in 4 patients (20%) and VRS 2 in 3 (15%) patients. The dosimetric analysis demonstrated noticeable variations between the rectum, rectal wall, and rectal wall subsegments. The dosimetric analysis of the rectum, rectal wall, and its mid and low segments with respect to rectoscopy findings showed that the higher dose endpoints V52.17Gy and V56.52Gy are associated with rectal mucosal injury. Conclusions: A thorough delineation of the rectal wall and its subsegments, together with the dosimetric analysis of these structures, may reduce late rectal toxicity. Dosimetric parameters such as V52.17Gy and V56.52Gy were identified to have a significant impact on rectal mucosal injury; additional dose endpoint validation and its relation to late GI toxicity is needed.

Towards Automation in Radiotherapy Planning: A Deep Learning Approach for the Delineation of Parotid Glands in Head and Neck Cancer.

The delineation of parotid glands in head and neck (HN) carcinoma is critical to assess radiotherapy (RT) planning. Segmentation processes ensure precise target position and treatment precision, facilitate monitoring of anatomical changes, enable plan adaptation, and enhance overall patient safety. In this context, artificial intelligence (AI) and deep learning (DL) have proven exceedingly effective in precisely outlining tumor tissues and, by extension, the organs at risk. This paper introduces a DL framework using the AttentionUNet neural network for automatic parotid gland segmentation in HN cancer. Extensive evaluation of the model is performed in two public and one private dataset, while segmentation accuracy is compared with other state-of-the-art DL segmentation schemas. To assess replanning necessity during treatment, an additional registration method is implemented on the segmentation output, aligning images of different modalities (Computed Tomography (CT) and Cone Beam CT (CBCT)). AttentionUNet outperforms similar DL methods (Dice Similarity Coefficient: 82.65% ± 1.03, Hausdorff Distance: 6.24 mm ± 2.47), confirming its effectiveness. Moreover, the subsequent registration procedure displays increased similarity, providing insights into the effects of RT procedures for treatment planning adaptations. The implementation of the proposed methods indicates the effectiveness of DL not only for automatic delineation of the anatomical structures, but also for the provision of information for adaptive RT support.

Exploring the occurrence and the risk factors of the desire for hastened death and depression in people with early-stage dementia in Greece.

OBJECTIVES: To assess the factors associated with desire for hastened death and depression in early-stage dementia as well as the association between them. Also, to explore the mediator and moderator role of age in the relationship between depression and desire for hasten death. METHODS: A prospective cross-sectional study including 100 patients diagnosed with early-stage dementia from a rehabilitation center between December 2018 and July 2019. Measurement tools used were the Mini-Mental State Examination, the Greek Montreal Cognitive Assessment, the Greek Schedule of Attitudes toward Hastened Death, and the Geriatric Depression Scale-15 item. Patients diagnosed with dementia as a result of Stroke history were excluded. RESULTS: Factors of multifactorial analysis significantly associated with desire for hastened death were as follows: age (p = 0.009), marital status (p = 0.001), and depression (p < 0.001). The factor significantly associated with depression was age (p = 0.001). Also, a mediation/moderation analysis has shown that depression and age are significant predictors of desire for hasten death. SIGNIFICANCE OF RESULTS: The desire for hastened death and depression in people diagnosed with early-stage dementia includes many components. Younger patients, men, higher educated patients, single, childless, and those with higher depression scores had higher desire for hastened death, while men and older patients had higher scores of desire for depression. Our study provides important information about the desire for hastened death and depression in early-stage dementia, their risk factors, and their association.

Preoperative chemoradiotherapy induces multiple pathways related to anti-tumour immunity in rectal cancer.

BACKGROUND: Rectal cancer treated with preoperative radiotherapy (RT) provides an interesting model to study changes induced on cancer cell immuno-phenotype that could be exploited by immunotherapy interventions to improve prognosis. MATERIALS AND METHODS: We assessed the expression of HLA-class-I, ß2-microglobulin, TAP1, PD-L1 and STING/IFNß in preoperative biopsies and respective post-RT surgical specimens from patients with rectal cancer (n = 27). The effect of radiation was further investigated in colorectal adenocarcinoma cell lines HT-29 and Caco-2. RESULTS: Rectal carcinomas exhibited extensive loss of expression of HLA-Class-I related molecules, which was restored in post-irradiation surgical specimens (P < 0.0001). RT induced the expression of IFNß and STING in cancer cells and tumour-infiltrating lymphocytes (P < 0.0001). In in vitro experiments, irradiation with 4 Gy or 10 Gy induced the expression of HLA-class-I protein (P < 0.001). PD-L1 levels were transiently induced for two days (P < 0.001). cGAS, STING, IFNß and the downstream genes (MX1, MX2, UBE2L6v2, IFI6v2 and IFI44) mRNA levels significantly increased after 3 × 8 Gy or 1 × 20 Gy irradiation (P < 0.001). TREX1 mRNA levels remained unaltered. CONCLUSIONS: RT induces the IFN-type-I pathway and the expression of HLA-class-I molecules on rectal carcinoma. The transient induction of PD-L1 expression suggests that long-course daily RT may sustain increased PD-L1 levels. Anti-PD-L1/PD-1 immunotherapy could block this immunosuppressive pathway.

Prostate Cancer Stem Cells: Biology and Treatment Implications.

Stem cells differentiate into mature organ/tissue-specific cells at a steady pace under normal conditions, but their growth can be accelerated during the process of tissue healing or in the context of certain diseases. It is postulated that the proliferation and growth of carcinomas are sustained by the presence of a vital cellular compartment resembling stem cells residing in normal tissues: 'stem-like cancer cells' or cancer stem cells (CSCs). Mutations in prostate stem cells can lead to the formation of prostate cancer. Prostate CSCs (PCSCs) have been identified and partially characterized. These express surface markers include CD44, CD133, integrin α2ß1, and pluripotency factors like OCT4, NANOG, and SOX2. Several signaling pathways are also over-activated, including Notch, PTEN/Akt/PI3K, RAS-RAF-MEK-ERK and HH. Moreover, PCSCs appear to induce resistance to radiotherapy and chemotherapy, while their presence has been linked to aggressive cancer behavior and higher relapse rates. The development of treatment policies to target PCSCs in tumors is appealing as radiotherapy and chemotherapy, through cancer cell killing, trigger tumor repopulation via activated stem cells. Thus, blocking this reactive stem cell mobilization may facilitate a positive outcome through cytotoxic treatment.

Surface-Guided Radiotherapy: Can We Move on from the Era of Three-Point Markers to the New Era of Thousands of Points?

The surface-guided radiotherapy (SGRT) technique improves patient positioning with submillimeter accuracy compared with the conventional positioning technique of lasers using three-point tattoos. SGRT provides solutions to considerations that arise from the conventional setup technique, such as variability in tattoo position and the psychological impact of the tattoos. Moreover, SGRT provides monitoring of intrafractional motion. PURPOSE: This literature review covers the basics of SGRT systems and examines whether SGRT can replace the traditional positioning technique. In addition, it investigates SGRT's potential in reducing positioning times, factors affecting SGRT accuracy, the effectiveness of live monitoring, and the impact on patient dosage. MATERIALS AND METHODS: This study focused on papers published from 2016 onward that compared SGRT with the traditional positioning technique and investigated factors affecting SGRT accuracy and effectiveness. RESULTS/CONCLUSIONS: SGRT provides the same or better results regarding patient positioning. The implementation of SGRT can reduce overall treatment time. It is an effective technique for detecting intrafraction patient motion, improving treatment accuracy and precision, and creating a safe and comfortable environment for the patient during treatment.

Psychometric Properties of the Greek Version of Demoralization Scale-II (DS-II) in Patients with Cancer.

Introduction: The concept of demoralization is used to describe situations of existential distress and self-perceived inability to effectively deal with stressors. The Demoralization Scale-II (DS-II) is a short and modified version of the original DS that measures the level of demoralization in patients. The purpose of this study is to evaluate the psychometric properties of the Greek version of the Greek Demoralisation Scale-II (DS-II GR) in the population of patients with cancer. Methods: The main tool used in this cross-sectional study is the DS-II GR translated and evaluated for its psychometric properties in a sample of 150 Greek patients with cancer. Exploratory factor analysis (EFA), confirmatory factor analysis (CFA), convergent validity, known groups' validity, cut-off points, internal consistency reliability and test-retest reliability were done. Results: According to the CFA, a two-factor model emerged with a different conceptual content and grouping than the original. The correlation coefficients between DS-II GR and Hospital Anxiety and Depression Scale-Greek (HADS-GR) The internal consistency of DS-II GR for factor 1, factor 2, and total score were measured with Cronbach's alpha and calculated to be 0.906, 0.810, and 0.913. Conclusion: The Greek version of the demoralization scale is reliable and valid for assessing demoralization in Greek patients with cancer.

Anti-Tumor Immunity and Preoperative Radiovaccination: Emerging New Concepts in the Treatment of Breast Cancer.

Neoadjuvant chemotherapy (NACT) for certain breast cancer (BC) subtypes confers significant tumor regression rates and a survival benefit for patients with a complete pathologic response. Clinical and preclinical studies have demonstrated that immune-related factors are responsible for better treatment outcomes, and thus, neoadjuvant immunotherapy (IO) has emerged as a means to further improve patient survival rates. Innate immunological "coldness", however, of specific BC subtypes, especially of the luminal ones, due to their immunosuppressive tumor microenvironment, hinders the efficacy of immune checkpoint inhibitors. Treatment policies aiming to reverse this immunological inertia are, therefore, needed. Moreover, radiotherapy (RT) has been proven to have a significant interplay with the immune system and promote anti-tumor immunity. This "radiovaccination" effect could be exploited in the neoadjuvant setting of BC and significantly enhance the effects of the already established clinical practice. Modern stereotactic irradiation techniques directed to the primary tumor and involved lymph nodes may prove important for the RT-NACT-IO combination. In this review, we provide an overview and critically discuss the biological rationale, clinical experience, and ongoing research underlying the interplay between neoadjuvant chemotherapy, anti-tumor immune response, and the emerging role of RT as a preoperative adjunct with immunological therapeutic implications in BC.

Immune Response and Immune Checkpoint Molecules in Patients with Rectal Cancer Undergoing Neoadjuvant Chemoradiotherapy: A Review.

It is well-established that tumor antigens and molecules expressed and secreted by cancer cells trigger innate and adaptive immune responses. These two types of anti-tumor immunity lead to the infiltration of the tumor's microenvironment by immune cells with either regulatory or cytotoxic properties. Whether this response is associated with tumor eradication after radiotherapy and chemotherapy or regrowth has been a matter of extensive research through the years, mainly focusing on tumor-infiltrating lymphocytes and monocytes and their subtypes, and the expression of immune checkpoint and other immune-related molecules by both immune and cancer cells in the tumor microenvironment. A literature search has been conducted on studies dealing with the immune response in patients with rectal cancer treated with neoadjuvant radiotherapy or chemoradiotherapy, assessing its impact on locoregional control and survival and underlying the potential role of immunotherapy in the treatment of this cancer subtype. Here, we provide an overview of the interactions between local/systemic anti-tumor immunity, cancer-related immune checkpoint, and other immunological pathways and radiotherapy, and how these affect the prognosis of rectal cancer patients. Chemoradiotherapy induces critical immunological changes in the tumor microenvironment and cancer cells that can be exploited for therapeutic interventions in rectal cancer.

Current status of locally advanced rectal cancer therapy and future prospects.

Rectal cancer treatment has been evolving ever since the beginning of the 20th century. Surgery was originally the only available method regardless of the extent of tumor invasion or nodal involvement status. Total mesorectal excision was established as the standard procedure in the early 1990 s. Advances in the utilization of radiation for rectal cancer led to the addition of radiotherapy (RT) combined with chemotherapy to the postoperative treatment algorithm. The promising results of the Swedish short-course preoperative RT set the basis for a number of large randomized trials investigating the efficacy of neoadjuvant RT or chemoradiotherapy (CRT) for advanced rectal cancer. Both short-course RT and long-course preoperative CRT compared favorably to adjuvant treatment and became the standard of choice for patients with extramural invasion or lymph node involvement. Recently, the focus of clinical research has been shifted towards total neoadjuvant therapy (TNT), delivering the whole course of RT and chemotherapy before surgery, and showing good tolerance and encouraging efficacy. Although targeted therapies haven't displayed a benefit in the neoadjuvant setting, preliminary evidence suggests impressive efficacy of immunotherapy in rectal carcinomas with mismatch-repair deficiency. In this review, we provide an in-depth critical overview of all significant randomized trials that have shaped the current treatment guidelines for locally advanced rectal cancer and discuss future trends for the treatment of this common malignancy.

Craniospinal Irradiation: A Dosimetric Comparison Between O-Ring Linac and Conventional C-arm Linac.

Purpose: The aim of this study was to perform a dosimetric evaluation between craniospinal irradiation volumetric modulated arc therapy plans designed for an O-Ring and a conventional C-arm Linac. Methods and Materials: Two adult patients were selected for this study. Two plans were designed one for a TrueBeam Edge and one for Halcyon O-ring Linac for each patient. The evaluation of the plans was conducted in terms of dose volume histogram analysis of the target volume and organs at risk (OARs) along with total plan monitor units and beam-on time. Paired sample t test was performed to compare Dmax and Dmean of OARs for each plan's comparison. The delivery of volumetric modulated arc therapy plans was evaluated using Octavius 4D phantom. Results: All plans demonstrated dose distributions with sufficient planned target volume conformity and homogeneity. The Homogeneity Index and Conformity Index for all plans were found comparable. The paired sample t test did not demonstrate significant difference in terms of Dmax and Dmean of OARs between plans for both patients. All plans met the threshold of 90%, with Halcyon plans having higher gamma passing rates. Conclusions: Craniospinal irradiation plans generated for Halcyon and Edge are equivalent in terms of plan quality and dose sparing at OARs. The small variations may have originated from the differences in beam profile or mean energy, the degree of the modulation for each plan and characteristics of multi leaf collimators for each treatment unit. Halcyon is able to deliver a distinctly faster treatment, but Edge provides an automatic rotational correction for patient positioning.

The molecular basis of immuno-radiotherapy.

PURPOSE: Radiotherapy (RT) and immunotherapy are powerful anti-tumor treatment modalities. Experimental research has demonstrated an important interplay between the cytotoxic effects of RT and the immune system. This systematic review provides an overview of the basics of anti-tumor immunity and focuses on the mechanisms underlying the interplay between RT and immune anti-tumor response that set the molecular basis of immuno-RT. CONCLUSIONS: An 'immunity acquired equilibrium' mimicking tumor dormancy can be achieved post-irradiation treatment, with the balance shifted toward tumor eradication or regrowth when immune cells' cytotoxic effects or cancer proliferation rate prevail, respectively. RT has both immunosuppressive and immune-enhancing properties. The latter effect is also known as radio-vaccination. Its mechanisms involve up- or down-regulation of membrane molecules, such as PD-L1, HLA-class-I, CD80/86, CD47, and Fas/CD95, that play a vital role in immune checkpoint pathways and increased cytokine expression (e.g. INFα,ß,γ, IL1,2, and TNFα) by cancer or immune cells. Moreover, the interactions of radiation with the tumor microenvironment (fibroblasts, tumor-infiltrating lymphocytes, monocytes, and dendritic cells are also an important component of radio-vaccination. Thus, RT may have anti-tumor vaccine properties, whose sequels can be exploited by immunotherapy agents to treat different cancer subtypes effectively.

Limited Cerebral Metastases in NSCLC: A Literature Review of SRS Versus Whole-brain Radiotherapy.

BACKGROUND/AIM: Brain metastases (BMs) are common in patients with non-small cell lung cancer (NSCLC). Whole-brain radiotherapy (WBRT) with or without corticosteroid use has historically been the first choice for most patients with BMs despite its negative impact on cognition and quality of life. However, stereotactic radiosurgery (SRS) has emerged as a safe and effective treatment and has been established for patients with limited, inoperable BMs. SRS and WBRT are either used separately or together, in an attempt to achieve the best possible local and distal control rates and even improve overall survival. A number of phase III trials have focused on answering the question which modality - SRS, WBRT or both - can achieve the best possible results. In this review, we present the existing data regarding the use of SRS compared with WBRT and their combination for NSCLC patients with limited, non-operable BMs. MATERIALS AND METHODS: A literature review was performed in PubMed, Medline, and the Cochrane Library databases from 1995 up to 2021. Principles outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement were followed. RESULTS: We identified seven randomised control trials (RCTs) that compared WBRT with WBRT plus SRS boost and four RCTs that compared SRS alone with SRS plus WBRT. CONCLUSION: Overall, addition of WBRT to SRS did not improve survival but had a positive effect on locoregional control.

Is anti-PD-1 immunotherapy a means for post-irradiation tumor clearance in head and neck cancer?

Chemo-radiotherapy is the standard treatment for locally advanced head-neck cancer (LA-HNC). However, about 30% of tumors do not respond or even progress shortly after the completion of radiotherapy. We investigated whether anti-PD1 immunotherapy can eradicate the irradiated tumor and reverse the ominous prognosis of these patients. We retrospectively analyzed a small series of 9 patients with LA-HNC who did not respond (6/9) or showed local disease progression (3/9) during chemo-radiotherapy and were treated with nivolumab anti-PD1 immunotherapy. Immunotherapy started 1.5 months after the end of radiotherapy. Out of 9 patients, 3 (33.3%) had a complete response and 3 (33.3%) partial response at 6 months after the onset of immunotherapy. Two patients are alive with no evidence of disease at 36 months. One more patient with partial response and without disease progression survived 16 months after therapy when he died from intercurrent disease. Immunotherapy showed an excellent tolerance profile. One patient developed an extensive skin rash on the 16th cycle. Anti-PD-1 immunotherapy after radiotherapy can lead to clearance of the remnant tumor and ameliorate the prognosis of patients. Randomized trials are necessary to establish post-irradiation immunotherapy as a standard of care in this ill-fated subgroup of HNC patients.

Synchronous bilateral chest wall irradiation with regional nodal irradiation: A literature review of techniques and a case study.

The optimal radiotherapy technique for patients requiring both breasts or chest walls simultaneous irradiation with or without regional nodal irradiation is currently under investigation. In the last decade several publications present case reports and case series of patients treated with adjuvant radiotherapy in both breasts or chest walls for synchronous bilateral breast cancer (SBBC) with modern radiotherapy techniques. This article presents a systematic review of relevant literature as well as a case report of a SBBC patient who received bilateral chest wall radiotherapy with regional nodal irradiation at our institution with Truebeam - Edge Linear Accelerator. Solid evidence is provided that the practice of avoiding adjuvant radiotherapy in SBBC out of fear of toxicity with older radiotherapy techniques is outdated. Modern techniques can safely and effectively deliver treatment to patients requiring both sides irradiation and even in mastectomy patients in need of regional nodal irradiation.

Early Prediction of Planning Adaptation Requirement Indication Due to Volumetric Alterations in Head and Neck Cancer Radiotherapy: A Machine Learning Approach.

BACKGROUND: During RT cycles, the tumor response pattern could affect tumor coverage and may lead to organs at risk of overdose. As such, early prediction of significant volumetric changes could therefore reduce potential radiation-related adverse effects. Nevertheless, effective machine learning approaches based on the radiomic features of the clinically used CBCT images to determine the tumor volume variations due to RT not having been implemented so far. METHODS: CBCT images from 40 HN cancer patients were collected weekly during RT treatment. From the obtained images, the Clinical Target Volume (CTV) and Parotid Glands (PG) regions of interest were utilized to calculate 104 delta-radiomics features. These features were fed on a feature selection and classification procedure for the early prediction of significant volumetric alterations. RESULTS: The proposed framework was able to achieve 0.90 classification performance accuracy while detecting a small subset of discriminative characteristics from the 1st week of RT. The selected features were further analyzed regarding their effects on temporal changes in anatomy and tumor response modeling. CONCLUSION: The use of machine learning algorithms offers promising perspectives for fast and reliable early prediction of large volumetric deviations as a result of RT treatment, exploiting hidden patterns in the overall anatomical characteristics.

Impact of Hippocampal Avoidance - Prophylactic Cranial Irradiation in Small Cell Lung Cancer Patients.

BACKGROUND/AIM: Prophylactic cranial irradiation (PCI) is a well-established treatment of small cell lung cancer (SCLC) patients following response to initial chemoradiotherapy. The benefit of PCI does, however, come at the cost of cognitive decline. This has been attributed to radiation-induced toxicity at the hippocampus, a crucial anatomic area for cognition. Modern radiotherapy techniques allow dose reduction at the hippocampal region. In this review, the safety profile, effect on cognition, and changes on brain imaging modalities of hippocampal avoidance-PCI (HA-PCI) will be presented, aiming to identify a potential clinical rationale for SCLC patients. MATERIALS AND METHODS: A systematic review of the literature was performed in Pubmed, Cochrane library databases and ClinicalTrials.gov with no past date limitations until 07/01/2022. Principles as outlined in the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement were followed. RESULTS: Eight studies published from 2015 to 2021 were included. CONCLUSION: HA-PCI is safe, yet its effect on neurocognition and imaging remains unclear, as studies have shown contradictory results.

Immunotherapy in HER2-Positive Breast Cancer: A Systematic Review.

Introduction: The clinical outcome of HER2-positive breast cancer patients changed with the use of anti-Her therapies, though it still remains an aggressive and fatal disease. Implementation of immune checkpoint inhibitors in HER2-positive Breast cancer is a concept supported by the reported biological and preclinical data. Methods: We conducted a systematic review of the current literature involving immune checkpoint inhibitors alone or in combination with targeted therapies or chemotherapy finalized or running in HER2-positive breast cancer. Results: Twelve clinical trials and 2 case reports were identified in our study. Conclusion: The reported clinical trials highlight that checkpoint inhibition seems to be promising in metastatic, neoadjuvant, and adjuvant settings of HER2-positive breast cancer.

Oral mucositis-related neuropathic pain in head and neck cancer patients receiving radiotherapy or chemo-radiotherapy. A prospective study.

PURPOSE: Pain due to oral-mucositis (OM) in head and neck cancer (HNC) patients receiving radiotherapy (RT) /chemo-radiotherapy (CRT) can be nociceptive and/or neuropathic. Neuropathic pain (NP) often remains underdiagnosed and untreated. This study's purpose was to identify the presence of OM-induced NP in HNC patients under RT/CRT. METHODS: Pain was assessed using a 0-10 numeric scale (NRS). At an NRS≥5 score, patients completed the Douleur Neuropathique 4 (DN4) questionnaire, where a score ≥4/10 indicates the presence of NP. Mucositis and xerostomia were assessed using the European Organization for Research and Treatment of Cancer and the NRS scales accordingly. Pain medication was documented. RESULTS: Forty patients were recruited; twenty-six (mean age 63.54±13.96 years) completed a DN4 (mean pain NRS 7.46±1.42); five (5/26, 19.23%) had a DN4≥4. The most common NP descriptors were "burning" (34.62%), "electric shocks" (30.77%) and "pins-and-needles" (30.77%). A direct correlation was observed between DN4 and pain, mucositis, and xerostomia (p<0.02). Pain medication was administered to fifteen patients (15/26, 57.69%). Adjuvant medication was administered to one patient with positive DN4 score. CONCLUSIONS: Five (5/26, 19%) of the patients with NRS≥5 developed NP; adjuvant medication to address NP was prescribed to one patient. NP is likely underdiagnosed and undertreated in the HNC population undergoing RT/RC.