Showing papers in "Current Oncology in 2022"

Immune Checkpoint Inhibitors in Cancer Therapy

Abstract: The discovery of immune checkpoint proteins such as PD-1/PDL-1 and CTLA-4 represents a significant breakthrough in the field of cancer immunotherapy. Therefore, humanized monoclonal antibodies, targeting these immune checkpoint proteins have been utilized successfully in patients with metastatic melanoma, renal cell carcinoma, head and neck cancers and non-small lung cancer. The US FDA has successfully approved three different categories of immune checkpoint inhibitors (ICIs) such as PD-1 inhibitors (Nivolumab, Pembrolizumab, and Cemiplimab), PDL-1 inhibitors (Atezolimumab, Durvalumab and Avelumab), and CTLA-4 inhibitor (Ipilimumab). Unfortunately, not all patients respond favourably to these drugs, highlighting the role of biomarkers such as Tumour mutation burden (TMB), PDL-1 expression, microbiome, hypoxia, interferon-γ, and ECM in predicting responses to ICIs-based immunotherapy. The current study aims to review the literature and updates on ICIs in cancer therapy.

Non-Small-Cell Lung Cancer in 2022: A Review for General Practitioners in Oncology

Abstract: Lung cancer is the leading cause of cancer death in Canada and a significant cause of morbidity for patients and their loved ones. There have been rapid advances in preventing, screening and treating this disease. Here, we present a contemporary review of treatment of non-small cell lung cancer in Canada based on current best practices. The focus of this review is to highlight recent data in screening for lung cancer, management of patients with early and locally-advanced non-small cell lung cancer, as well as management of patients with metastatic disease. There is a special focus on the incorporation of immunotherapy into practice and its associated toxicities.

Immunotherapy in Gastric Cancer

Abstract: Immune checkpoint inhibition is a new standard of targeted therapy in the treatment of advanced or metastatic gastric cancer (GC) and is represented in various combinations with and without chemotherapy in every therapy line within clinical trials. In advanced adenocarcinoma of GC, gastroesophageal junction cancer (GEJC) and esophageal cancer (EC), the combination of nivolumab and chemotherapy in first-line therapy improves overall survival (OS) in PD-L1 (programmed cell death protein 1)-positive patients with approval in Europe (PD-L1 CPS (combined positivity score) ≥ 5), USA and Taiwan (CHECKMATE-649) and pembrolizumab plus chemotherapy for GEJC and EC in Europe (CPS ≥ 10) and the USA (KEYNOTE-590). Furthermore, pembrolizumab plus trastuzumab and chemotherapy show clear benefits in OS and are approved as first-line treatment of Her2 (human epidermal growth factor receptor-2)-positive tumors in the USA (KEYNOTE-811). Nivolumab demonstrates superior OS regardless of PD-L1 expression in third-line therapy with approval in Japan (ATTRACTION-02) and pembrolizumab prolonged the duration of response in PD-L1 positive patients with approval in the USA in PD-L1 CPS ≥ 1 patients (KEYNOTE-059). This review reflects the rationale and current results of phase II and III clinical trials investigating various immune checkpoint inhibitors targeting PD-L1/1 and CTLA (anticytotoxic T-lymphocyte-associated antigen)-4 in combination with and without chemotherapy and Her2-targeted therapy in GC.

Exosomal Non-Coding RNAs: New Insights into the Biology of Hepatocellular Carcinoma

Abstract: Exosomes, extracellular vesicles with a diameter of 40 to 160 nm, are among the smallest extracellular vesicles released by cells. They deliver different cargoes, including proteins, DNAs, and RNAs, and facilitate communication between cells to coordinate a variety of physiological and pathological functions. Hepatocellular carcinoma (HCC) is the sixth common malignant tumor and the fourth leading cause of cancer-related death worldwide. Its molecular mechanism remains largely unknown, and there is a lack of reliable and noninvasive biomarkers for early diagnosis and prognosis prediction. Mounting evidence has shown that exosomes carry a variety of ncRNAs, such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), which play critical roles in the occurrence and progression of HCC. In this review, we summarize the recent findings of exosomal miRNAs, lncRNAs, and circRNAs in HCC from their impact on the development of HCC to their potential applications in the diagnosis and treatment of HCC.

Autophagy Agents in Clinical Trials for Cancer Therapy: A Brief Review

Abstract: Autophagy has been of novel interest since it was first demonstrated to have effect in Burkitt’s lymphoma. Since that time, the autophagy agents chloroquine and hydroxychloroquine have become the only FDA (Food and Drug Administration)-approved autophagy inhibitors. While not approved for cancer therapy, there are ongoing clinical trials to evaluate their safety and efficacy. Pevonedistat has emerged as a novel inhibitor through the neddylation pathway and is an autophagy activator. This paper summarizes and presents current clinical trials for hydroxychloroquine (HCQ), chloroquine (CQ), and Pevonedistat for the clinician.

Circulating Exosomal microRNAs as Predictive Biomarkers of Neoadjuvant Chemotherapy Response in Breast Cancer

Abstract: Background: Neoadjuvant chemotherapy (NACT) is an increasingly used approach for treatment of breast cancer. The pathological complete response (pCR) is considered a good predictor of disease-specific survival. This study investigated whether circulating exosomal microRNAs could predict pCR in breast cancer patients treated with NACT. Method: Plasma samples of 20 breast cancer patients treated with NACT were collected prior to and after the first cycle. RNA sequencing was used to determine microRNA profiling. The Cancer Genome Atlas (TCGA) was used to explore the expression patterns and survivability of the candidate miRNAs, and their potential targets based on the expression levels and copy number variation (CNV) data. Results: Three miRNAs before that NACT (miR-30b, miR-328 and miR-423) predicted pCR in all of the analyzed samples. Upregulation of miR-127 correlated with pCR in triple-negative breast cancer (TNBC). After the first NACT dose, pCR was predicted by exo-miR-141, while miR-34a, exo-miR182, and exo-miR-183 predicted non-pCR. A significant correlation between the candidate miRNAs and the overall survival, subtype, and metastasis in breast cancer, suggesting their potential role as predictive biomarkers of pCR. Conclusions: If the miRNAs identified in this study are validated in a large cohort of patients, they might serve as predictive non-invasive liquid biopsy biomarkers for monitoring pCR to NACT in breast cancer.

Classification of Brain Tumor from Magnetic Resonance Imaging Using Vision Transformers Ensembling

Abstract: The automated classification of brain tumors plays an important role in supporting radiologists in decision making. Recently, vision transformer (ViT)-based deep neural network architectures have gained attention in the computer vision research domain owing to the tremendous success of transformer models in natural language processing. Hence, in this study, the ability of an ensemble of standard ViT models for the diagnosis of brain tumors from T1-weighted (T1w) magnetic resonance imaging (MRI) is investigated. Pretrained and finetuned ViT models (B/16, B/32, L/16, and L/32) on ImageNet were adopted for the classification task. A brain tumor dataset from figshare, consisting of 3064 T1w contrast-enhanced (CE) MRI slices with meningiomas, gliomas, and pituitary tumors, was used for the cross-validation and testing of the ensemble ViT model’s ability to perform a three-class classification task. The best individual model was L/32, with an overall test accuracy of 98.2% at 384 × 384 resolution. The ensemble of all four ViT models demonstrated an overall testing accuracy of 98.7% at the same resolution, outperforming individual model’s ability at both resolutions and their ensembling at 224 × 224 resolution. In conclusion, an ensemble of ViT models could be deployed for the computer-aided diagnosis of brain tumors based on T1w CE MRI, leading to radiologist relief.

Uncommon EGFR Compound Mutations in Non-Small Cell Lung Cancer (NSCLC): A Systematic Review of Available Evidence

Abstract: Compound epidermal growth factor receptor (EGFR) mutations represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations. We conducted a systematic review to investigate the available data on this patients’ subgroup. Overall, we found a high heterogeneity in the incidence of compound mutations (4–26% of total EGFR mutant cases), which is dependent on the different testing methods adopted and the specific mutations considered. In addition, the relative incidence of distinct compound subclasses identified is reported with extreme variability in different studies. Preclinical and clinical data, excluding de novo EGFR exon 20 p.T790M compound mutations, show good responses with EGFR tyrosine kinase inhibitors (TKIs) (combined common mutations: response rate (RR) ≥ 75% with either first- or second-generation TKIs; combined common plus uncommon: RR 40–80% and 100% with first-generation TKIs and afatinib, respectively; combined uncommon: RR 20–70%, ~80% and ~75% with first-generation TKIs, afatinib and osimertinib, respectively). Overall, data are consistent in supporting the use of EGFR TKIs in treating compound EGFR mutations, taking into account different sensitivity profile of accompanying EGFR mutations for selecting the most adequate EGFR TKI for individual patients.

Endometrial Cancer: Transitioning from Histology to Genomics

Abstract: Endometrial carcinoma (EC) is traditionally treated with surgery and adjuvant treatment depending on clinicopathological risk factors. The genomic analysis of EC in 2013 and subsequent studies using immunohistochemistry have led to the current EC molecular classification into: polymerase epsilon mutated (POLEmut), p53 abnormal (p53abn), mismatch repair deficient (MMRd), and no specific molecular profile (NSMP). The four groups have prognostic value and represent a promising tool for clinical decision-making regarding adjuvant treatment. Molecular classification was integrated into the recent European Society of Gynecologic Oncology (ESGO) management guidelines. POLEmut EC has favorable outcomes and retrospective studies found that omitting adjuvant treatment is safe in this group; two prospective clinical trials, PORTEC-4 and TAPER, are ongoing to assess this. p53 abn is associated with increased recurrence, decreased survival, and benefitted from chemotherapy in the PORTEC-3 subgroup molecular analysis. The clinical trials PORTEC-4a and CANSTAMP will prospectively assess this. MMRd and NSMP groups have intermediate prognosis and will likely continue to rely closely on clinicopathological features for adjuvant treatment decisions. In addition, the molecular classification has led to exploring novel treatments such as checkpoint inhibitors. Overall, the molecular perspective on EC and associated clinical trials will likely refine EC risk stratification to optimize care and avoid overtreatment.

ROS-1 Fusions in Non-Small-Cell Lung Cancer: Evidence to Date

Abstract: The ROS-1 gene plays a major role in the oncogenesis of numerous tumors. ROS-1 rearrangement is found in 0.9–2.6% of non-small-cell lung cancers (NSCLCs), mostly lung adenocarcinomas, with a significantly higher rate of women, non-smokers, and a tendency to a younger age. It has been demonstrated that ROS-1 is a true oncogenic driver, and tyrosine kinase inhibitors (TKIs) targeting ROS-1 can block tumor growth and provide clinical benefit for the patient. Since 2016, crizotinib has been the first-line reference therapy, with two-thirds of the patients’ tumors responding and progression-free survival lasting ~20 months. More recently developed are ROS-1-targeting TKIs that are active against resistance mechanisms appearing under crizotinib and have better brain penetration. This review summarizes current knowledge on ROS-1 rearrangement in NSCLCs, including the mechanisms responsible for ROS-1 oncogenicity, epidemiology of ROS-1-positive tumors, methods for detecting rearrangement, phenotypic, histological, and molecular characteristics, and their therapeutic management. Much of this work is devoted to resistance mechanisms and the development of promising new molecules.

Cutaneous Adverse Events Associated with Immune Checkpoint Inhibitors: A Review Article

Abstract: Immune checkpoint inhibitors (ICIs) have emerged as novel options that are effective in treating various cancers. They are monoclonal antibodies that target cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death-ligand 1 (PD-L1). However, activation of the immune systems through ICIs may concomitantly trigger a constellation of immunologic symptoms and signs, termed immune-related adverse events (irAEs), with the skin being the most commonly involved organ. The dermatologic toxicities are observed in nearly half of the patients treated with ICIs, mainly in the form of maculopapular rash and pruritus. In the majority of cases, these cutaneous irAEs are self-limiting and manageable, and continuation of the ICIs is possible. This review provides an overview of variable ICI-mediated dermatologic reactions and describes the clinical and histopathologic presentation. Early and accurate diagnosis, recognition of severe toxicities, and appropriate management are key goals to achieve the most favorable outcomes and quality of life in cancer patients.

Applications of Artificial Intelligence in Screening, Diagnosis, Treatment, and Prognosis of Colorectal Cancer

Abstract: Colorectal cancer (CRC) is one of the most common cancers worldwide. Accurate early detection and diagnosis, comprehensive assessment of treatment response, and precise prediction of prognosis are essential to improve the patients’ survival rate. In recent years, due to the explosion of clinical and omics data, and groundbreaking research in machine learning, artificial intelligence (AI) has shown a great application potential in clinical field of CRC, providing new auxiliary approaches for clinicians to identify high-risk patients, select precise and personalized treatment plans, as well as to predict prognoses. This review comprehensively analyzes and summarizes the research progress and clinical application value of AI technologies in CRC screening, diagnosis, treatment, and prognosis, demonstrating the current status of the AI in the main clinical stages. The limitations, challenges, and future perspectives in the clinical implementation of AI are also discussed.

Satisfaction with Telemedicine for Cancer Pain Management: A Model of Care and Cross-Sectional Patient Satisfaction Study

Abstract: Background: Since cancer pain requires complex modalities of care, the proper strategy for addressing its telemedicine-based management should be better defined. This study aimed to trace a pathway for a progressive implementation of the telemedicine process for the treatment of pain in the setting of cancer patients. Methods: The features of the model were investigated to dissect the dropout from the telemedicine pathway. A cross-sectional patient satisfaction study was conducted. The degree of satisfaction was evaluated through a developed 22-item questionnaire (Likert scale 0–7). Results: A total of 375 video consultations for 164 patients (mean age 62.9 years) were performed through remote consultations for cancer pain management between March 2021 and February 2022. After the exclusion of 72 patients, 92 (56.1%) were included in the analysis. The dropout ratio was 8.7%. The number of visits and pharmacological therapies for neuropathic pain correlated with the risk for readmission (p < 0.05). Overall, the satisfaction was very high (mean > 5.5 for all items). Conclusion: Feedback from patients reflected high satisfaction rates with the care provided. A methodological approach based on the degree of satisfaction combined with the analysis of the pathways can help to implement the quality of a service provided through telemedicine. While not without limitations, our hybrid protocol can be useful for addressing cancer pain through a patient-centered approach.

A Portrait of SARS-CoV-2 Infection in Patients Undergoing Hematopoietic Cell Transplantation: A Systematic Review of the Literature

Abstract: The management of COVID-19 in hematopoietic cell transplant (HCT) recipients represents a special challenge given the variable states of immune dysregulation and altered vaccine efficacy in this population. A systematic search (Ovid Medline and Embase on 1 June 2021) was needed to better understand the presenting features, prognostic factors, and treatment options. Of 897 records, 29 studies were identified in our search. Most studies reporting on adults and pediatric recipients described signs and symptoms that were typical of COVID-19. Overall, the mortality rates were high, with 21% of adults and 6% of pediatric HCT recipients succumbing to COVID-19. The factors reported to be associated with increased mortality included age (HR = 1.21, 95% CI 1.03–1.43, p = 0.02), ICU admission (HR = 4.42, 95% CI 2.25–8.65, p < 0.001 and HR = 2.26, 95% CI 1.22–4.20, p = 0.01 for allogeneic and autologous HCT recipients), and low platelet count (OR = 21.37, 95% CI 1.71–267.11, p = 0.01). Performance status was associated with decreased mortality (HR = 0.83, 95% CI 0.74–0.93, p = 0.001). A broad range of treatments was described, although no controlled studies were identified. The risk of bias, using the Newcastle–Ottawa scale, was low. Patients undergoing HCT are at a high risk of severe morbidity and mortality associated with COVID-19. Controlled studies investigating potential treatments are required to determine the efficacy and safety in this population.

Point of Care Molecular Testing: Community-Based Rapid Next-Generation Sequencing to Support Cancer Care

Abstract: Abstract Purpose: Biomarker data are critical to the delivery of precision cancer care. The average turnaround of next-generation sequencing (NGS) reports is over 2 weeks, and in-house availability is typically limited to academic centers. Lengthy turnaround times for biomarkers can adversely affect outcomes. Traditional workflows involve moving specimens through multiple facilities. This study evaluates the feasibility of rapid comprehensive NGS using the Genexus integrated sequencer and a novel streamlined workflow in a community setting. Methods: A retrospective chart review was performed to assess the early experience and performance characteristics of a novel approach to biomarker testing at a large community center. This approach to NGS included an automated workflow utilizing the Genexus integrated sequencer, validated for clinical use. NGS testing was further integrated within a routine immunohistochemistry (IHC) service, utilizing histotechnologists to perform technical aspects of NGS, with results reported directly by anatomic pathologists. Results: Between October 2020 and October 2021, 578 solid tumor samples underwent genomic profiling. Median turnaround time for biomarker results was 3 business days (IQR: 2–5). Four hundred eighty-one (83%) of the cases were resulted in fewer than 5 business days, and 66 (11%) of the cases were resulted simultaneously with diagnosis. Tumor types included lung cancer (310), melanoma (97), and colorectal carcinoma (68), among others. NGS testing detected key driver alterations at expected prevalence rates: lung EGFR (16%), ALK (3%), RET (1%), melanoma BRAF (43%), colorectal RAS/RAF (67%), among others. Conclusion: This is the first study demonstrating clinical implementation of rapid NGS. This supports the feasibility of automated comprehensive NGS performed and interpreted in parallel with diagnostic histopathology and immunohistochemistry. This novel approach to biomarker testing offers considerable advantages to clinical cancer care.

Drug Treatment for Advanced Hepatocellular Carcinoma: First-Line and Beyond

Abstract: Hepatocellular carcinoma (HCC) has high mortality. The option of systemic therapy has increased significantly over the past five years. Sorafenib was the first multikinase inhibitor, introduced in 2007, as a treatment option for HCC, and it was the only effective systemic treatment for more than ten years. It was not until 2017 that several breakthroughs were made in the development of systemic strategies. Lenvatinib, another multikinase inhibitor, stood out successfully after sorafenib, and has been applied to clinical use in the first-line setting. Other multikinase inhibitors such as regorafenib, ramucirumab and cabozantinib, were approved in quick succession as second-line therapies. Concurrently, immune checkpoint inhibitors (ICIs) have readily become established treatments for many solid tumors, including HCC. The most studied ICIs to date, target programmed cell death-1 (PD-1), its ligand PD-L1, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). These ICIs have demonstrated efficacy in treating advanced HCC. More recently, combination of bevacizumab and atezolizumab (ICI targeting PD-L1) was approved as the gold-standard first-line therapy. Combination of ICIs with nivolumab and ipilimumab was also approved in the second-line setting for those who failed sorafenib. At the moment, numerous clinical trials in advanced HCC are underway, which will bring continuous change to the management, and increase the survival, for patients with advanced HCC. Our review article: (1) summarizes United States Food and Drug Administration (US FDA) approved systemic therapies in advanced HCC, (2) reports the evidence of currently approved treatments, (3) discusses potential drugs/drug combinations being currently tested in phase III clinical trials, and (4) proposes possible future directions in drug development for advanced HCC.

A Case Series of Metastatic Malignant Gastrointestinal Neuroectodermal Tumors and Comprehensive Genomic Profiling Analysis of 20 Cases

Abstract: Malignant gastrointestinal neuroectodermal tumor (GNET) is an ultra-rare soft tissue sarcoma, therefore often misdiagnosed and has no available standard treatment. Here, we report 3 cases of metastatic GNET with variable clinical courses. Our small case series as well as extensive literature review, further support that GNET is a spectrum of diseases with variable inherent biology and prognosis. Surgical management in the setting of recurrent/metastatic disease may be appropriate for GNET with indolent nature. Response to systemic treatments including chemotherapy and targeted treatments is variable, likely related to heterogenous biology as well. Furthermore, we retrospectively identified 20 additional GNET cases from Foundation Medicine’s genomic database and expanded on their clinicopathological and genomic features. Comprehensive genomic profiling (CGP) with DNA and RNA sequencing of this cohort, in the course of clinical care, demonstrated recurrent EWSR1 chromosomal rearrangements and a sparsity of additional recurrent or driver genomic alterations. All cases had low tumor mutational burden (TMB) and were microsatellite stable.

Immunotherapy as a Neoadjuvant Therapy for a Patient with Hepatocellular Carcinoma in the Pretransplant Setting: A Case Report

Abstract: Systemic combination therapy of immune checkpoint inhibitors and vascular endothelial growth factors have provided the basis for improved outcomes in select patients with unresectable or metastatic hepatocellular carcinoma. However, for patients with resectable disease, surgery alone or an orthotopic liver transplant remains the standard of care. Within the realms of transplant oncology, neoadjuvant systemic therapy is currently being evaluated as a potential strategy to improve outcomes in patients with HCC. Here, we report excellent response with significant downstaging in a safe manner after neoadjuvant treatment with atezolizumab and bevacizumab in a patient diagnosed with poorly differentiated HCC. As a result of the significant response observed with safe outcomes, the patient was listed for orthotopic liver transplant (OLT) evaluation and transplanted successfully.

Current Advances in Immune Checkpoint Inhibition and Clinical Genomics in Upper Tract Urothelial Carcinoma: State of the Art

Abstract: Upper tract urothelial carcinoma (UTUC) is a rare and challenging-to-treat malignancy. In most patients it is a sporadic tumor entity, less commonly it falls on the spectrum of Lynch syndrome, an autosomal dominant familial tumor syndrome. Localized UTUC with high-risk features as well as the metastatic disease scenario might require systemic therapy. Platinum-based combination chemotherapy is currently the recommended management option. However, the introduction of immune checkpoint inhibitors into the therapeutic armamentarium has led to a paradigm shift in treatment standards. Immunotherapy has been shown to be safe and effective in treating at least metastatic UTUC, although UTUC-specific high-level evidence is still lacking. Recent technological advances and noteworthy research efforts have greatly improved the general understanding of the biological landscape of UTUC. According to the main findings, UTUC represent a particular subtype of urothelial carcinoma frequently associated with activated FGFR3 signaling, a luminal–papillary phenotype and a T-cell-depleted microenvironment. This improved knowledge promises precision oncology approaches that match treatment decision strategies and genomic profile to ultimately result in better clinical outcomes. The aim of this review was to summarize the main currently available evidence on immune checkpoint inhibition and clinical genomics in UTUC.

HPV Vaccination: An Underused Strategy for the Prevention of Cancer

Abstract: Human papillomavirus (HPV) vaccination prevents cervical, head and neck, and anogenital cancers. However, global HPV vaccine coverage falls short of global targets and has seen unexpected and dramatic declines in some countries. This paper synthesizes the impact of HPV on the global burden of cancer and the potential benefit of HPV vaccination. Approximately 5% of the world’s cancers are specifically attributed to HPV. While the greatest global burden of HPV is cervical cancers in low- and middle-income countries, HPV-associated head and neck cancers are increasing in high-income countries and have surpassed cervical cancer as the primary HPV-associated cancer in some countries. Therefore, it is also critical to improve gender-neutral HPV vaccination. Understanding the modifiable drivers of vaccine acceptance and uptake is important for increasing HPV vaccination. The Behavioural and Social Drivers of Vaccination framework is broadly applied to identify key factors associated with HPV vaccination including domains concerning practical issues, motivation, social processes, and thinking and feeling. Among the behavioural strategies available to reduce the incidence and mortality of cancer, increasing HPV vaccination stands out as having unrealized potential to prevent disease, financial cost, and psychological distress. An understanding of the shifting burden of HPV and the factors associated with vaccination can be leveraged to regularly measure these factors, develop interventions to promote vaccine uptake, and improve global HPV vaccine coverage. Future research in diverse contexts is necessary to investigate the barriers and facilitators of global HPV vaccination.

Osseous Union after Mandible Reconstruction with Fibula Free Flap Using Manually Bent Plates vs. Patient-Specific Implants: A Retrospective Analysis of 89 Patients

Abstract: The aim of this monocentric, retrospective clinical study was to evaluate the status of osseous union in uni- and poly-segmental mandible reconstructions regarding conventional angle-stable manually bent osteosynthesis plates (Unilock 2.0 mm) versus titan laser-melted PSI patient-specific implant’s (PSI). The clinical impact of PSI’s high stiffness fixation methods on bone healing and regeneration is still not well addressed. The special interest was in evaluating the ossification of junctions between mandible and fibula and between osteotomized fibula free flap (FFF) segments. Panoramic radiograph (OPT), computed tomography (CT) scans, or cone-beam CTs (CBCT) of patients who underwent successful FFF for mandible reconstruction from January 2005 to December 2020 were analyzed. A total number of 89 cases (28 females (31.5%), 61 males (68.5%), mean age 58.2 ± 11.3 years, range: 22.8–82.7 years) fulfilled the chosen inclusion criteria for analysis (conventional: n = 44 vs. PSI: n = 45). The present study found an overall incomplete ossification (IOU) rate of 24.7% (conventional: 13.6% vs. PSI: 35.6%; p = 0.017) for mandible to fibula and intersegmental junctions. Between osteotomized FFF segments, an IOU rate of 16% was found in the PSI-group, while no IOU was recorded in the conventional group (p = 0.015). Significant differences were registered for IOU rates in poly-segmental (p = 0.041), and lateral (p = 0.016) mandibular reconstructions when PSI was used. Multivariate logistic regression analysis identified plate exposure and type of plate used as independent risk factors for IOU. Previous or adjuvant radiotherapy did not impact incomplete osseous union in the evaluated study sample. PSI is more rigid than bent mini-plates and shields functional mechanical stimuli, and is the main reason for increasing the rate of incomplete ossification. To enhance the functional stimulus for ossification it has to be discussed if patient-specific implants can be designed to be thinner, and should be divided into segmental plates. This directs chewing forces through the bone and improves physiological bone remodeling.

A Narrative Review on the Collection and Use of Electronic Patient-Reported Outcomes in Cancer Survivorship Care with Emphasis on Symptom Monitoring

Abstract: Electronic patient-reported outcome (ePRO) applications promise great added value for improving symptom management and health-related quality of life. The aim of this narrative review is to describe the collection and use of ePROs for cancer survivorship care, with an emphasis on ePRO-symptom monitoring. It offers many different perspectives from research settings, while current implementation in routine care is ongoing. ePRO collection optimizes survivorship care by providing insight into the patients’ well-being and prioritizing their unmet needs during the whole trajectory from diagnosis to end-of-life. ePRO-symptom monitoring can contribute to timely health risk detection and subsequently allow earlier intervention. Detection is optimized by automatically generated alerts that vary from simple to complex and multilayered. Using ePRO-symptoms during in-hospital consultation enhances the patients’ conversation with the health care provider before making informed decisions about treatments, other interventions, or self-management. ePRO(-symptoms) entail specific implementation issues and complementary ethics considerations. The latter is due to privacy concerns, digital divide, and scarcity of adequately representative data for particular groups of patients.

The Psychosocial Impact of COVID-19 on Older Adults with Cancer: A Rapid Review

Abstract: Background: Older adults with cancer are amongst the most vulnerable population to be negatively impacted by COVID-19 due to their likelihood of comorbidities and compromised immune status. Considering the longevity of the pandemic, understanding the subjective perceptions and psychosocial concerns of this population may help ameliorate the psychological aftermath. In this review, we systematically analyze the literature surrounding the psychosocial impact and coping strategies among older adults with cancer within the context of COVID-19. Methods: We conducted a rapid review of literature following PRISMA guidelines between January 2020 to August 2021 using (1) MEDLINE, (2) Embase, (3) CINAHL, and (4) PsychINFO and keyword searches for “cancer” and “COVID-19” focused on adults 65 years or older. Results: Of the 6597 articles screened, 10 met the inclusion criteria. Based on the included articles, the psychosocial impact of COVID-19 was reported under four domains, (1) impact of COVID-19 on quality of life (QoL), (2) concerns related to COVID-19, (3) coping with the impact of COVID-19, and (4) recommendations for future care. Results pertaining to perceived quality of life were inconsistent across the included articles. The most common concerns related to: contracting COVID-19, survivorship transitions, and feelings of isolation. Coping strategies reported by older adults included: spiritual care, lived experience, acceptance, and positive reinterpretation. Conclusions: We found many psychosocial impacts of the pandemic on older adults with cancer. The findings from this review can inform interventions related to shared decision-making and tailored patient care in the future.

Triple-Negative Breast Cancer: A Review of Current Curative Intent Therapies

Abstract: Breast cancer is the most commonly diagnosed malignancy in women, with triple-negative breast cancer (TNBC) accounting for 10–20% of cases. Historically, fewer treatment options have existed for this subtype of breast cancer, with cytotoxic chemotherapy playing a predominant role. This article aims to review the current treatment paradigm for curative-intent TNBC, while also reviewing potential future developments in this landscape. In addition to chemotherapy, recent advances in the understanding of the molecular biology of TNBC have led to promising new studies of targeted and immune checkpoint inhibitor therapies in the curative-intent setting. The appropriate selection of TNBC patient subgroups with a higher likelihood of benefit from treatment is critical to identify the best treatment approach.

Genomic Landscape of Non-Small Cell Lung Cancer (NSCLC) in East Asia Using Circulating Tumor DNA (ctDNA) in Clinical Practice

Abstract: Plasma-based next-generation sequencing (NGS) has demonstrated the potential to guide the personalized treatment of non-small cell lung cancer (NSCLC). Inherent differences in mutational genomic profiles of NSCLC exist between Asian and Western populations. However, the published mutational genomic data of NSCLC has largely focused on Western populations. We retrospectively analyzed results from comprehensive NGS of plasma (Guardant360®) from patients with advanced non-squamous NSCLC, as seen in clinical practice. Tests were ordered between January 2016 and December 2020 in Hong Kong, Korea, Taiwan, Japan and Southeast Asia. The assay identified single-nucleotide variants (SNV), insertions and deletions, and fusions and amplifications in 74 genes. In total, 1608 plasma samples from patients with advanced non-squamous NSCLC were tested. The median turnaround time for test results was 7 days. Of the samples with detectable ctDNA (85.6%), 68.3% had alterations in at least one NCCN-recommended NSCLC biomarker. EGFR driver mutations were most frequent (48.6%), followed by alterations of KRAS (7.9%), ERBB2 (4.1%) and ALK (2.5%). Co-mutations of EGFR and KRAS occurred in 4.7% of samples. KRAS G12C was identified in 18.6% of all samples with KRAS mutations. Common mutations, such as exon 19 deletions and L858R, accounted for 88.4% of EGFR driver mutations. Among the samples with any EGFR driver mutation, T790M was present in 36.9%, including 7.7% with additional alterations associated with osimertinib resistance (MET amplification, C797X). Comprehensive plasma-based NGS provided the timely and clinically informative mutational genomic profiling of advanced non-squamous NSCLC in East Asian patients.

Current and Future Biomarkers for Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinoma

Abstract: With the introduction of immunotherapy, significant improvement has been made in the treatment of head and neck squamous cell carcinoma (HNSCC). However, only a small subset of patients with HNSCC benefit from immunotherapy. The current biomarker, a programmed cell death protein ligand 1 (PD-L1) expression that is widely used in treatment decision making for advanced HNSCC, has only a moderate predictive value. Additionally, PD-L1-based assay has critical inherent limitations due to its highly dynamic nature and lack of standardization. With the advance in molecular techniques and our understanding of biology, more reliable, reproducible, and practical novel biomarkers are being developed. These include but are not limited to neoantigen/mutation characteristics, immune transcriptomes, tumor-infiltrating immune cell composition, cancer epigenomic, proteomics and metabolic characteristics, and plasma-based and organoid assays.

Artificial Intelligence System for Predicting Prostate Cancer Lesions from Shear Wave Elastography Measurements

Abstract: (1) Objective: To design an artificial intelligence system for prostate cancer prediction using the data obtained by shear wave elastography of the prostate, by comparing it with the histopathological exam of the prostate biopsy specimens. (2) Material and methods: We have conducted a prospective study on 356 patients undergoing transrectal ultrasound-guided prostate biopsy, for suspicion of prostate cancer. All patients were examined using bi-dimensional shear wave ultrasonography, which was followed by standard systematic transrectal prostate biopsy. The mean elasticity of each of the twelve systematic biopsy target zones was recorded and compared with the pathological examination results in all patients. The final dataset has included data from 223 patients with confirmed prostate cancer. Three machine learning classification algorithms (logistic regression, a decision tree classifier and a dense neural network) were implemented and their performance in predicting the positive lesions from the elastographic data measurements was assessed. (3) Results: The area under the curve (AUC) results were as follows: for logistic regression—0.88, for decision tree classifier—0.78 and for the dense neural network—0.94. Further use of an upsampling strategy for the training set of the neural network slightly improved its performance. Using an ensemble learning model, which combined the three machine learning models, we have obtained a final accuracy of 98%. (4) Conclusions: Bi-dimensional shear wave elastography could be very useful in predicting prostate cancer lesions, especially when it benefits from the computational power of artificial intelligence and machine learning algorithms.

The Chemo-Gut Pilot Study: Associations between Gut Microbiota, Gastrointestinal Symptoms, and Psychosocial Health Outcomes in a Cross-Sectional Sample of Young Adult Cancer Survivors

Abstract: Chemotherapy adversely affects the gut microbiota, inducing dysbiosis, and negatively impacts gastrointestinal (GI) and psychosocial health during treatment, but little is known about the long-term effects or how these factors are related. Methods: This cross-sectional pilot study investigated the effects of chemotherapy on the gut microbiota, GI symptoms, and psychosocial outcomes in cancer survivors aged 18–39 years old, compared to healthy controls. Gut microbial diversity and composition were assessed from stool samples using 16S rRNA gene sequencing. Results: Survivors (n = 17) and healthy controls (n = 18) participated. Mean age at diagnosis was 31 years (±5.3). Mean time off treatment was 16.9 months (±16.4). Survivors had more severe GI symptoms, poorer psychosocial health, and increased relative abundance of Selenomondales, Veilloneliaceae, and Intestinibacter. In survivors, Lachnospiraceae, Ruminococcaceae and Intestinibacter correlated with psychosocial symptoms, while diarrhea correlated positively with Lachnospiraceae. Results are statistically significant. Survivors ≤6 months post-treatment had lower alpha diversity than survivors >6 months post-treatment (p = 0.04) and controls (p = 0.19). Conclusion: This small exploratory study demonstrates potential long-term gut microbial dysbiosis in cancer survivors, which may be associated with psychosocial symptoms. Larger trials concurrently and longitudinally examining gut microbiota, GI symptoms, and psychosocial outcomes are needed.

The Role of Surgical Approaches in the Multi-Modal Management of Adult Craniopharyngiomas

Abstract: Craniopharyngiomas are rare, benign primary brain tumors that arise from remnants of the craniopharyngeal duct epithelium within the sellar and suprasellar region. Despite their benign biology, they may cause significant morbidity, secondary to involvement of nearby eloquent neural structures, such as the pituitary gland, hypothalamus, and optic apparatus. Historically, aggressive surgical resection was the treatment goal to minimize risk of tumor recurrence via open transcranial midline, anterolateral, and lateral approaches, but could lead to clinical sequela of visual, endocrine, and hypothalamic dysfunction. However, recent advances in the endoscopic endonasal approach over the last decade have mostly supplanted transcranial surgery as the optimal surgical approach for these tumors. With viable options for adjuvant radiation therapy, targeted medical treatment, and alternative minimally invasive surgical approaches, the management paradigm for craniopharyngiomas has shifted from aggressive open resection to more minimally invasive but maximally safe resection, emphasizing quality of life issues, particularly in regards to visual, endocrine, and hypothalamic function. This review provides an update on current multi-modal approaches for craniopharyngiomas, highlighting the modern surgical treatment paradigm for this disease entity.

The Use of Virtual Care in Patients with Hematologic Malignancies: A Scoping Review

Abstract: There is increasing interest from cancer patients and their healthcare providers in the use of virtual care in routine clinical practice. In the setting of hematologic malignancy, where patients often undergo complex and immunodepleting treatments, understanding how to use virtual care safely and effectively is critically important. We aimed to describe the use of virtual care in patients with hematologic malignancies and to examine physician- and patient-reported outcomes in the form of a systematic scoping review. An electronic search of PubMed, Ovid MEDLINE, Elsevier Embase, Scopus, and EBSCO CINAHL was conducted from January 2000 to April 2021. A comprehensive search strategy was used to identify relevant articles, and data were extracted to assess the study design, population, setting, patient characteristics, virtual care platform, and study results. Studies were included if they described the use of virtual care for patients with hematologic malignancies; commentaries were excluded. Fifteen studies met the inclusion criteria after abstract and full-text review. Three studies found that app-based tools were effective in monitoring patient symptoms and triggering alerts for more urgent follow-up. Four studies described the use of phone-based interventions. Five studies found that videoconferencing, with both physicians and oncology nurses, was highly rated by patients. Emerging themes included high levels of patient satisfaction across all domains of virtual care. Provider satisfaction scores were rated lower than patient scores, with concerns about technical issues leading to challenges with virtual care. Four studies found that virtual care allowed providers to promptly respond to patient concerns, especially when patients were experiencing side-effects or had questions about their treatment. Overall, the use of virtual care in patients with hematologic malignancies appears feasible, and resulted in high patient satisfaction. Further research is needed in order to evaluate the optimal method of integrating virtual care into clinical practice.