Long-term health-related quality of life in head and neck cancer survivors: A large multinational study.

Head and neck cancer (HNC) patients suffer from a range of health-related quality of life (HRQoL) issues, but little is known about their long-term HRQoL. This study explored associations between treatment group and HRQoL at least 5 years' post-diagnosis in HNC survivors. In an international cross-sectional study, HNC survivors completed the European Organization for Research and Treatment of Cancer (EORTC) quality of life core questionnaire (EORTC-QLQ-C30) and its HNC module (EORTC-QLQ-H&N35). Meaningful HRQoL differences were examined between five treatment groups: (a) surgery, (b) radiotherapy, (c) chemo-radiotherapy, (d) radiotherapy ± chemotherapy and neck dissection and (e) any other surgery (meaning any tumour surgery that is not a neck dissection) and radiotherapy ± chemotherapy. Twenty-six sites in 11 countries enrolled 1105 survivors. They had a median time since diagnosis of 8 years, a mean age of 66 years and 71% were male. After adjusting for age, sex, tumour site and UICC stage, there was evidence for meaningful differences (10 points or more) in HRQoL between treatment groups in seven domains (Fatigue, Mouth Pain, Swallowing, Senses, Opening Mouth, Dry Mouth and Sticky Saliva). Survivors who had single-modality treatment had better or equal HRQoL in every domain compared to survivors with multimodal treatment, with the largest differences for Dry Mouth and Sticky Saliva. For Global Quality of Life, Physical and Social Functioning, Constipation, Dyspnoea and Financial Difficulties, at least some treatment groups had better outcomes compared to a general population. Our data suggest that multimodal treatment is associated with worse HRQoL in the long-term compared to single modality.

Shedding Light on Colorectal Cancer: An In Vivo Raman Spectroscopy Approach Combined with Deep Learning Analysis.

Raman spectroscopy has emerged as a powerful tool in medical, biochemical, and biological research with high specificity, sensitivity, and spatial and temporal resolution. Recent advanced Raman systems, such as portable Raman systems and fiber-optic probes, provide the potential for accurate in vivo discrimination between healthy and cancerous tissues. In our study, a portable Raman probe spectrometer was tested in immunosuppressed mice for the in vivo localization of colorectal cancer malignancies from normal tissue margins. The acquired Raman spectra were preprocessed, and principal component analysis (PCA) was performed to facilitate discrimination between malignant and normal tissues and to highlight their biochemical differences using loading plots. A transfer learning model based on a one-dimensional convolutional neural network (1D-CNN) was employed for the Raman spectra data to assess the classification accuracy of Raman spectra in live animals. The 1D-CNN model yielded an 89.9% accuracy and 91.4% precision in tissue classification. Our results contribute to the field of Raman spectroscopy in cancer diagnosis, highlighting its promising role within clinical applications.

Nanoparticle-Mediated Radiotherapy: Unraveling Dose Enhancement and Apoptotic Responses in Cancer and Normal Cell Lines.

Cervical cancer remains a pressing global health concern, necessitating advanced therapeutic strategies. Radiotherapy, a fundamental treatment modality, has faced challenges such as targeted dose deposition and radiation exposure to healthy tissues, limiting optimal outcomes. To address these hurdles, nanomaterials, specifically gold nanoparticles (AuNPs), have emerged as a promising avenue. This study delves into the realm of cervical cancer radiotherapy through the meticulous exploration of AuNPs' impact. Utilizing ex vivo experiments involving cell lines, this research dissected intricate radiobiological interactions. Detailed scrutiny of cell survival curves, dose enhancement factors (DEFs), and apoptosis in both cancer and normal cervical cells revealed profound insights. The outcomes showcased the substantial enhancement of radiation responses in cancer cells following AuNP treatment, resulting in heightened cell death and apoptotic levels. Significantly, the most pronounced effects were observed 24 h post-irradiation, emphasizing the pivotal role of timing in AuNPs' efficacy. Importantly, AuNPs exhibited targeted precision, selectively impacting cancer cells while preserving normal cells. This study illuminates the potential of AuNPs as potent radiosensitizers in cervical cancer therapy, offering a tailored and efficient approach. Through meticulous ex vivo experimentation, this research expands our comprehension of the complex dynamics between AuNPs and cells, laying the foundation for their optimized clinical utilization.

Extended Analysis of Raman Spectra Using Artificial Intelligence Techniques for Colorectal Abnormality Classification.

Raman spectroscopy (RS) techniques are attracting attention in the medical field as a promising tool for real-time biochemical analyses. The integration of artificial intelligence (AI) algorithms with RS has greatly enhanced its ability to accurately classify spectral data in vivo. This combination has opened up new possibilities for precise and efficient analysis in medical applications. In this study, healthy and cancerous specimens from 22 patients who underwent open colorectal surgery were collected. By using these spectral data, we investigate an optimal preprocessing pipeline for statistical analysis using AI techniques. This exploration entails proposing preprocessing methods and algorithms to enhance classification outcomes. The research encompasses a thorough ablation study comparing machine learning and deep learning algorithms toward the advancement of the clinical applicability of RS. The results indicate substantial accuracy improvements using techniques like baseline correction, L2 normalization, filtering, and PCA, yielding an overall accuracy enhancement of 15.8%. In comparing various algorithms, machine learning models, such as XGBoost and Random Forest, demonstrate effectiveness in classifying both normal and abnormal tissues. Similarly, deep learning models, such as 1D-Resnet and particularly the 1D-CNN model, exhibit superior performance in classifying abnormal cases. This research contributes valuable insights into the integration of AI in medical diagnostics and expands the potential of RS methods for achieving accurate malignancy classification.

Serious Long-Term Effects of Head and Neck Cancer from the Survivors' Point of View.

The long-term problems of head and neck cancer survivors (HNCS) are not well known. In a cross-sectional international study aimed at exploring the long-term quality of life in this population, 1114 HNCS were asked to state their two most serious long-term effects. A clinician recorded the responses during face-to-face appointments. A list of 15 example problems was provided, but a free text field was also available. A total of 1033 survivors responded to the question. The most frequent problems were 'dry mouth' (DM) (n = 476; 46%), 'difficulty swallowing/eating' (DSE) (n = 408; 40%), 'hoarseness/difficulty speaking' (HDS) (n = 169; 16%), and 'pain in the head and neck' (PHN) (n = 142; 14%). A total of 5% reported no problems. Logistic regression adjusted for age, gender, treatment, and tumor stage and site showed increased odds of reporting DM and DSE for chemo-radiotherapy (CRT) alone compared to surgery alone (odds ratio (OR): 4.7, 95% confidence interval (CI): 2.5-9.0; OR: 2.1, CI: 1.1-3.9), but decreased odds for HDS and PHN (OR: 0.3, CI: 0.1-0.6; OR: 0.2, CI: 0.1-0.5). Survivors with UICC stage IV at diagnosis compared to stage I had increased odds of reporting HDS (OR: 1.9, CI: 1.2-3.0). Laryngeal cancer survivors had reduced odds compared to oropharynx cancer survivors of reporting DM (OR: 0.4, CI: 0.3-0.6) but increased odds of HDS (OR: 7.2, CI: 4.3-12.3). This study provides evidence of the serious long-term problems among HNCS.

Oral Side Effects in Patients with Metastatic Renal Cell Carcinoma Receiving the Antiangiogenic Agent Pazopanib-Report of Three Cases.

Pazopanib is a potent multi-kinase inhibitor that hinders angiogenesis and blocks tumor growth. It has been approved for the treatment of metastatic renal cell carcinoma (mRCC) and advanced soft tissue sarcoma. There is emerging evidence that bleeding is a common adverse effect of pazopanib and other targeted therapies in patients with mRCC. In addition, jaw osteonecrosis related to pazopanib was recently described in the literature. We report three cases of patients with mRCC who developed adverse oral events related to pazopanib. The first patient, treated with pazopanib as monotherapy, presented with gingival bleeding and oral burning sensation. The other two patients receiving pazopanib as monotherapy and pazopanib followed by sunitinib, respectively, presented complaining about mandibular pain; a diagnosis of medication-related osteonecrosis of the jaw (MRONJ) was rendered in both cases. Gingival bleeding and MRONJ may develop as oral side effects of pazopanib use. The cases presented here aim to alert and inform health care professionals about the risk of adverse oral events in patients with mRCC receiving the antiangiogenic agent pazopanib.

Pharmacological Management of Neuropathic Pain after Radiotherapy in Head and Neck Cancer Patients: A Systematic Review.

Background: Neuropathic pain (NP) in head and neck cancer (HNC) patients represents a treatment challenge. Most studies investigating drugs against NP are conducted in patients suffering with diabetic neuropathy or postherpetic neuralgia, while data are limited in cancer pain management. Additionally, regarding cancer therapy-related NP, most of the studies do not focus on HNC patients. The aim of this review is to identify the studies on systematically administered medication for NP management that included HNC patients under radiotherapy. Methods: A systematic literature search was performed, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in PubMed, Cochrane Library, Web of Science and ClinicalTrials.gov on 30 October 2021. The medical subject heading (MeSH) terms were ("head and neck cancer" OR "tumor") AND "neuropathic pain" AND "medication" AND "radiotherapy." The Cochrane Collaboration tool was used for quality assessment. Results: The search identified 432 articles. Three more articles were identified after searching the reference lists of the retrieved articles. A total of 10 articles met the eligibility inclusion criteria and were included in this review; 6 on gabapentin, 1 on pregabalin, 1 on nortriptyline, 1 on methadone, and 1 on ketamine. Statistically significant results in pain reduction compared to placebo or standard pain medication were found in the studies on pregabalin (p = 0.003), methadone (p = 0.03), ketamine (p = 0.012), and in two out of six gabapentin studies (p < 0.004). Two of the studies (both concerning gabapentin) had no comparison arm. Conclusions: Treatments including pregabalin, methadone, ketamine, and gabapentin were found to provide pain relief against HNC NP. While there is a plethora of pharmacological treatments available for the management of NP, only a few studies have been conducted regarding the pharmacological management of therapy-related NP in HNC patients. More studies should be conducted regarding the pharmacological approaches in HNC therapy-related NP so that specific treatment algorithms can be developed.

Raman Spectroscopy: A Personalized Decision-Making Tool on Clinicians' Hands for In Situ Cancer Diagnosis and Surgery Guidance.

Accurate in situ diagnosis and optimal surgical removal of a malignancy constitute key elements in reducing cancer-related morbidity and mortality. In surgical oncology, the accurate discrimination between healthy and cancerous tissues is critical for the postoperative care of the patient. Conventional imaging techniques have attempted to serve as adjuvant tools for in situ biopsy and surgery guidance. However, no single imaging modality has been proven sufficient in terms of specificity, sensitivity, multiplexing capacity, spatial and temporal resolution. Moreover, most techniques are unable to provide information regarding the molecular tissue composition. In this review, we highlight the potential of Raman spectroscopy as a spectroscopic technique with high detection sensitivity and spatial resolution for distinguishing healthy from malignant margins in microscopic scale and in real time. A Raman spectrum constitutes an intrinsic "molecular finger-print" of the tissue and any biochemical alteration related to inflammatory or cancerous tissue state is reflected on its Raman spectral fingerprint. Nowadays, advanced Raman systems coupled with modern instrumentation devices and machine learning methods are entering the clinical arena as adjunct tools towards personalized and optimized efficacy in surgical oncology.

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.

Alveolar bone histological necrosis observed prior to extractions in patients, who received bone-targeting agents.

OBJECTIVE: We reported the alveolar bone histology prior to dental extractions in cancer patients, who received bone-targeting agents (BTA). SUBJECTS AND METHODS: Fifty-four patients were included. Patients underwent extractions, and bone biopsies were taken. RESULTS: Extractions were performed due to pain, swelling, purulence, fistula, and numbness, not responding to treatment, in 40 patients (group A); extractions due to asymptomatic, non-restorable teeth, were performed in 14 patients (group B). Complete alveolar jaw bone histological necrosis was observed in 28 of 40 (70%) patients of group A and none of group B (p < .001). The development of clinical osteonecrosis (MRON) was assessed in 44 patients; 10 patients, who were also treated with Low Level Laser Treatments-LLLT, were excluded from this analysis, as the alternative therapies were a confounding factor. Twelve patients, with alveolar bone histological necrosis prior to extraction, developed medication-related osteonecrosis of the jaw (MRONJ) compared with two patients with vital or mixed vital/non-vital bone (p < .0007). BTAs >1 year and concurrent targeted therapy were also significantly associated with MRONJ (p = .016 and p = .050). CONCLUSION: Pain, swelling, purulence, fistula, and numbness were significantly associated with complete bone histological necrosis prior to extractions and increased MRONJ development. Research is justified to explore whether histological necrosis represents an early stage of osteonecrosis.

Circulating anti-phospholipase A2 receptor antibodies as a diagnostic and prognostic marker in Greek patients with idiopathic membranous nephropathy - a retrospective cohort study.

INTRODUCTION: Circulating autoantibodies against phospholipase A2 receptor (anti-PLA2R) are recognized as key elements in the pathogenesis of idiopathic membranous nephropathy. In current clinical practice, they are increasingly gaining attention as novel tools for diagnosis and disease monitoring. We investigated the diagnostic and prognostic utility of anti-PLA2R antibody measurements in Greek patients with biopsy-proven membranous nephropathy. METHODS: Anti-PLA2R levels were measured in serum samples from 33 patients at diagnosis using ELISA and were associated with treatment outcome. Moreover, serial anti-PLA2R measurements were performed in 15 patients under different clinical conditions and level alterations were correlated with disease activity. RESULTS: Positive anti-PLA2R antibodies at diagnosis were found in 16 of 33 patients (48.5%). Anti-PLA2R levels were independently associated with the achievement of complete remission of nephrotic syndrome after immunosuppressive treatment compared to partial remission (p = 0.02, R2 = 0.265, 95%CI -0.019 to -0.0003). Higher detectable antibody levels at diagnosis were correlated with higher proteinuria levels (r = 0.813, p = 0.0001, 95%CI 0.532 to 0.933) and lower eGFR at the end of follow-up (r = -0.634, p = 0.0083, 95%CI -0.86 to -0.202). Serial antibody measurements during follow-up showed that anti-PLA2R titers were significantly reduced at the end of treatment after complete remission was achieved, remained low under sustained clinical remission, and increased during relapse. CONCLUSIONS: Our findings confirm the usefulness of anti-PLA2R measurements in the diagnosis of idiopathic membranous nephropathy. Low levels of anti-PLA2R antibodies at diagnosis are predictive of complete remission of nephrotic syndrome following immunosuppressive treatment. Serial anti-PLA2R measurements correlate well with clinical status throughout the follow-up period and could be used routinely for monitoring of disease activity and treatment planning.

Osteonecrosis of the jaw related to non-antiresorptive medications: a systematic review.

INTRODUCTION: The reporting of osteonecrosis of the jaw (ONJ) related to anticancer agents without known antiresorptive properties (non-antiresorptives), such as antiangiogenics, tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, immune checkpoint inhibitors, and cytotoxic chemotherapy is increasing. OBJECTIVE: To review characteristics of ONJ in cancer patients receiving non-antiresorptives. METHODS: A systematic review of the literature between 2009 and 2017 was conducted by the Bone Study Group of MASCC/ISOO. RESULTS: Of 6249 articles reviewed and from personal communication, 42 ONJ cases related to non-antiresorptives were identified. No gender predilection was noted. Median age was 60 years and ONJ stage 2 was most common, with predilection for posterior mandible. Exposed bone, pain, and infection were common at diagnosis. In comparison to bone targeting agents (BTAs), radiology, histology, and management were similar, with medication often discontinued. Delayed diagnosis (median 8 weeks) was noted. Important differences included earlier time to ONJ onset (median 20 weeks), absence of trigger event (40%), and greater likelihood of healing and shorter healing time (median 8 weeks) as compared to BTA-related ONJ. Gastrointestinal cancers predominated, followed by renal cell carcinomas compared to breast, followed by prostate cancers in BTA-related ONJ, reflecting different medications. CONCLUSIONS: Data about non-antiresorptive-related ONJ is sparse. This type of ONJ may have better prognosis compared to the BTA-related ONJ, suggested by greater likelihood of healing and shorter healing time. However, the delay in diagnosis highlights the need for more education. This is the first attempt to characterize ONJ associated with different non-antiresorptives, including BRAF and immune checkpoint inhibitors.

Blood natural killer activity is reduced in men with occupational stress and job insecurity working in a university.

PURPOSE: To examine the immune response to job strain and insecurity of 88 men working in a university, divided according to age and type of employment. METHODS: Anxiety, job strain, job insecurity and subjective symptoms were measured by questionnaires. Blood NK cytotoxic activity was determined by an in vitro method and lymphocyte subpopulations by flow-cytometry analysis. RESULTS: Employees (over 40 years old) in a library showed higher values of job strain, anxiety and subjective symptoms and lower blood NK activity than the controls. The young employees with temporary employment showed high job insecurity and reduced blood NK activity, while the young sanitary staff with temporary position showed normal immune response. NK cytotoxic activity of the recruited men was negatively correlated with anxiety, work load and job insecurity. CONCLUSIONS: Not only anxiety and depression but also high levels of job strain and/or insecurity may affect the health status by reducing blood NK activity.