Standard Oncological Treatment Research Articles

Informing a Future Clinician-Led Virtual Reality Experience Through Oncology Caregivers' Pre-Treatment Preparation Experiences.

The purpose of this study was to 1) describe oncology caregivers' pre-treatment preparation experiences, 2) elicit their feedback about approaches to improve the pre-treatment preparation experience, and 3) explore the potential use of visual aids into the pre-treatment education experience that will inform future clinician-led VR experiences. Using a qualitative descriptive design and convenience sampling technique, adult oncology caregivers were recruited to complete anonymous demographic and qualitative surveys posted on social media sites (i.e. American Cancer Society, Facebook, and LinkedIn) and a university supported community research registry (i.e. Pitt + Me). Demographic data were calculated using descriptive analyses (frequency and percentage) and qualitative data were analyzed using an inductive coding approach. Participants (N=18) were mostly female (n=13, 72%), white (n=14, 78%), married (n=14, 78%), and had a college degree or higher (n=16, 89%). They categorically ranged in age from 26 years to above 65 years, with the majority (n=11, 61%) between 36-55 years of age. Caregivers described the cancer information as overwhelming and in need of additional side effect information and emotional support. To meet their unmet needs, participants suggested providing additional resources, different approaches to learning, better explanation of processes and procedures, diverse emotional support, and more interactions with the oncology team. Clinician created VR experiences designed for and informed by oncology caregivers do not exist yet. VR could provide an alternative pediogogical approach to complement standard oncology treatment preparation. These study findings begin the exploration into innovative preparation approaches that could meet oncology caregivers' unmet emotional and educational needs during a stressful period. There is a dearth of clinicians creating and testing VR experiences for patients, let alone caregivers. Oncology caregivers are the unseen 'backbone' supporting their loved one and providing an innovative modality to support them could improve outcomes. VR has the potential improve outcomes for caregivers, which may improve outcomes for patients.

The Next Chapter in Cancer Diagnostics: Advances in HPV-Positive Head and Neck Cancer.

Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC), particularly oropharyngeal squamous cell carcinoma (OPSCC), is an increasingly prevalent pathology worldwide, especially in developed countries. For diagnosing HPV in HNSCC, the combination of p16 immunohistochemistry (IHC) and polymerase chain reaction (PCR) offers high sensitivity and specificity, with p16 IHC being a reliable initial screen and PCR confirming HPV presence. Advanced techniques like next-generation sequencing (NGS) and RNA-based assays provide detailed insights but are primarily used in research settings. Regardless of HPV status, standard oncological treatments currently include surgery, radiation, and/or chemotherapy. This conventional approach does not account for the typically better prognosis of HPV-positive HNSCC patients, leading to increased chemo/radiation-induced secondary morbidities and reduced quality of life. Therefore, it is crucial to identify and detect HPV positivity and other molecular characteristics of HNSCC to personalize treatment strategies. This comprehensive review aims to summarize current knowledge on various HPV detection techniques and evaluate their advantages and disadvantages, with a focus on developing methodologies to identify new biomarkers in HPV-positive HNSCC. The review discusses direct and indirect HPV examination in tumor tissue, DNA- and RNA-based detection techniques, protein-based markers, liquid biopsy potentials, immune-related markers, epigenetic markers, novel biomarkers, and emerging technologies, providing an overall insight into the current state of knowledge.

O-311 Oncological treatments have limited effects on the fertility prognosis in testicular cancer: A systematic review and meta-analysis

Abstract Study question What is the prevalence of infertility defined by azoospermia, failure to achieve paternity or the usage of cryosperm after oncological treatments in testicular cancer? Summary answer The overall prevalence of infertility (95% CI) is 14% (9-21%) after all therapy types and 4% (2-10%) in a pooled subgroup of good-prognosis patients. What is known already Testicular cancer is the most common solid tumor among young men in the reproductive phase between 15 and 45 years. More than 95% of the patients become long-term survivors and up to 77% of cancer survivors report an interest in paternity after completing cancer treatment. Most guidelines recommend that physicians should counsel their patients about sperm cryopreservation before initiating gonadotoxic therapy. However, few studies have assessed fertility parameters after testicular cancer therapies over the last twenty years. Thus, this very first meta-analysis in a large pooled study population of patients functions as the best approximation of fertility prognosis so far. Study design, size, duration The systematic review and meta-analysis is part of the FertiTOX project (www.fertitox.com) which aims to close the gap of data regarding gonadotoxicity of cancer therapies to enable more accurate counselling regarding fertility preservation. It was performed on all published studies since 2000 that have reported the prevalence of azoospermia, the failure to achieve a pregnancy over 12 months of regular unprotected sexual intercourse or the usage of cryosperm after oncological treatments of unilateral testicular cancer. Participants/materials, setting, methods A systematic literature search was conducted in Medline, Embase and Cochrane in December 2022. For the systematic review, studies with men after all types of unilateral testicular cancer were included. For the meta-analysis, studies with unspecified treatments, < 10 patients for outcome evaluation or rare tumours were excluded. Infertility was defined as azoospermia, failure to achieve paternity or the usage of cryosperm. The quality of the individual studies was assessed using the Newcastle-Ottawa Scale. Main results and the role of chance A total of 126 studies remained following screening of the abstracts and fulltext for the subject of the study. Of these, 30 studies including 13718 men with a history of unilateral testicular cancer were eligible and analysed for qualitative synthesis. Sample sizes ranged from 17 to 4846 patients with a follow-up from 1-30 (mean 6.5) years. Histology included seminomas (43.9%), non-seminomas (49.6%) and sex cord or stromal tumors (0.01%). Treatment comprised active surveillance after unilateral orchidectomy (32.7%), radiotherapy (23.1%), standard or low-dose chemotherapy (33.7%) and high-dose chemotherapy (1.4%). Spermiograms after treatment were analysed in 17 studies. A quantitative synthesis was performed in 23 studies. To account for heterogeneity observed among studies, a random-effects model was used to estimate the prevalence and its 95% CI. The overall pooled prevalence of infertility (95% CI) in men with unilateral testicular cancer after standard oncological treatment was 14% (9-21%). Azoospermia after all types of oncological treatments appeared in 8% (6-12%) of the pooled study population. For good-prognosis patients who received standard therapy (i.e. surgery with or without retroperitoneal lymph node dissection, low- or standard dosed platin-based chemotherapy up to four cycles and / or radiotherapy), the overall prevalence of infertility was only 4% (2-10%). Limitations, reasons for caution First, the majority of the studies based on either questionnaire or register data with evident selection bias. Second, further subgroup analysis was impossible due to predominantly mixed treatment cohorts allowing only an approximation of standard therapy effects. Third, infertility might have occurred due to factors besides the oncological therapy. Wider implications of the findings Our meta-analysis includes all men with fertility outcome after testicular cancer therapy. Despite the overall low prevalence of infertility, sperm cryopreservation should still be recommended since it is unclear which therapy will follow after surgery and since there is no large longitudinal data for the various individual treatment effects. Trial registration number PROSPERO (Registry number CRD42023384057)

Trends and updates on the epidemiology of cancer-associated thrombosis: a systematic review

For cancer patients, cancer-associated thrombosis (CAT) is a serious complication. An updated epidemiology of CAT over the last ten years is summarized in this review. A comprehensive analysis of pertinent population cohort research released between 2011 and 2024 was carried out. In patients with unselected cancers, the 12-month incidence of CAT is roughly 3-5% (9-fold increase vs to the matched non-cancer population); however, in patients with advanced cancers requiring systemic therapy, the risk rises to 6-8% (20-fold increase vs. to the matched non-cancer population). Anticoagulation use and adherence have improved, but the risk of recurrence is still high, at 5-8% at 6 months and 7-15% at 12 months. The type, stage, and treatment of cancer, a history of venous thromboembolism (VTE), prolonged hospitalization or immobilization, and obesity are significant clinical predictors of the development of CAT. The modified Vienna-CATS and EHR-CAT have the best performance (area under the curve 0.68-0.71) among the clinical risk prediction scores for CAT using the original Khorana score backbone that has been externally validated. However, additional research is required to guarantee appropriate implementation and utilization of these models. Even with contemporary antineoplastic treatments, CAT is still a major complication for cancer patients. We encourage interdisciplinary partnerships among hematologists, data scientists, epidemiologists, and oncologists to guarantee the integration of customized VTE risk evaluation into standard oncologic treatment.

THE PROTECT TRIAL - PREOPERATIVE EXERCISE THERAPY FOR PATIENTS WITH CANCER: A PILOT RANDOMISED-CONTROLLED TRIAL

INTRODUCTION & AIMS Prehabilitation exercise is a promising strategy in oncology to optimise pre-operative cardiorespiratory fitness (CRF), which could reduce post-operative complications, mortality and enhance quality of life. This trial aimed to investigate the safety, feasibility, and effects of an aerobic prehabilitation exercise program in breast, colorectal, and prostate cancer patients. Primary outcomes were serious adverse events (SAE), adverse events (AE), participant adherence and compliance. Secondary outcomes were CRF variables and patient well-being. METHODS A CONSORT-compliant pilot randomised controlled trial (RCT) was conducted at a regional hospital in Ballarat, Australia. Prostate, breast, and colorectal cancer patients scheduled for surgery were randomised 1:1 into prehabilitation (PREHAB) or usual care (UCARE). PREHAB involved aerobic exercises informed by baseline cardio-pulmonary testing findings, with supervised sessions every two/three days for a minimum of 2-weeks. UCARE involved standard oncology treatment. Data on physical activity (actigraphy), resting vitals, and post-operative outcomes (Clavien-Dindo) were also collected. RESULTS Among 47 approached patients, 23 were randomised. Overall, 11 patients were analysed in the PREHAB and 9 in the UCARE groups. No SAEs were reported, and an exercise-related AE occurred every 756 minutes (total 3780). Participants attended 91.3% of PREHAB sessions. PREHAB participants attended 5.25 (SD = 2.16) sessions and had an average of 15 days from baseline testing to surgery. No significant time x group interactions were observed in V̇O2peak, ventilatory threshold (VT), or overall patient well-being (p = 0.90, 0.58, 0.82); PREHAB achieved small within-group increases in absolute V̇O2peak and VT (+4.9% and +1.8%, respectively). CONCLUSIONS The PROTECT trial demonstrated the safety and feasibility of delivering prehabilitation, revealing small clinically relevant increases in CRF fitness measures. Potentially due to the sample size, no significant improvements were observed in well-being or post-operative complications; future research should prioritise larger-scale RCTs further to explore the benefits of prehabilitation in this population.

The Impact on Survival of Neoadjuvant Treatment Interruptions in Locally Advanced Rectal Cancer Patients.

The standard oncologic treatment of locally advanced rectal cancer is long-course radio-chemotherapy followed by surgery and adjuvant chemotherapy. This can result in a lengthy total treatment duration, sometimes up to one year from the diagnosis. Interruptions to neoadjuvant treatment can occur for a variety of reasons, forced or unforced. The main purpose of this study is to analyze the survival data of locally advanced rectal cancer patients who received neoadjuvant treatment and to find a cut-off point showing exactly how many days of interruption of neoadjuvant treatment the risk of death or disease relapse increases. We conducted a retrospective study on 299 patients with locally advanced rectal cancer using survival analysis (Kaplan-Meier curve and Cox regression) to determine survival probabilities for overall survival, local control, and disease-free survival. Patients with 0 to 3 days of neoadjuvant therapy interruption had a higher overall survival probability compared to patients with 4 or more days (90.2% compared to 57.9%, p-value < 0.001), hazard ratio 5.89 (p < 0.001). Local control and disease-free survival had a higher probability in patients with 0-2 days of interruption compared to people with 3 or more days (94% vs. 75.4%, and 82.2% vs. 50.5%, respectively, both p-values < 0.001). Patients with tumoral or nodal downstaging experienced fewer days of interruption than patients with no downstage. These findings reinforce the need for radiation oncologists to be well-organized when starting neoadjuvant treatment for rectal cancer, in order to anticipate and prevent potential treatment interruptions and achieve the best therapeutic results.

SURG-40. AWAKE CRANIOTOMY IN A MIDDLE-INCOME COUNTRY. CHALLENGES AND TECHNICAL NUANCES

Abstract OBJECTIVES Describe the first experience in this technically challenging procedure RESULTS on morbidity INTRODUCTION Awake craniotomy allows for maximal safe resection and lower incidence of adverse events. Nonetheless, it represents a technical challenge. METHODS We enroll forty patients, 18 women, and 22 men. Due to the lack of a navigation system, craniometrics points became paramount to craniotomy planning. Ultrasound is used to compensate for brain shift and confirm the tumor's exact location. We engaged in cortical and subcortical mapping and clinical evaluation of motor and sensory functions. Linguistic tests were applied. The first 24 hours are in the ICU, and an MRI is obtained. RESULTS The mean age was 51, and the mean Karfnosky scale was 80. The median size was 12 cm3. Locations were: Thirteen precentral gyri. Ten insular cortex. Eight cingulate gyri. Six supplementary motor gyri Two Supramarginal gyri. One paracentral lobe tumor. Four patients had obese morbidity, three had depression, and two had a midline displacement treated with steroids. Intraoperative, we encountered three seizures managed with cold saline, two speech arrest, and one transient hand motor deficit. Post-op adverse events were one central facial paralysis, one upper limb, and one lower limb paresthesias; all improved after 72 hours. The median length of stay is 48 hours. The median extent of resection is 93%. The mean KPS was 80 at discharge. We undertook a median of 18 months follow-up. 38 Glioblastomas(GMB) and 2 Low-Grade Gliomas(LGG) were found. The standard oncology treatment was Temozolomide and stereotaxic radiosurgery(SRS). The median time from surgery to SRS was 4.3 months. The median SRS marginal and maximal dose were 15Gy and 26Gy. The median overall survival(OS) was sixteen months, and the Progression-free survival(PFS) was ten months. CONCLUSION An awake craniotomy without the navigation system is possible; however, careful planning is essential.

Fusion proteins development strategies and their role as cancer therapeutic agents.

Cancer continues to be leading cause of morbidity and mortality despite decades of research and advancement in chemotherapy. Most tumors can be reduced via standard oncology treatments, such as chemotherapy, radiotherapy, and surgical resection, and they frequently recur. Significant progress has been made since targeted cancer therapy inception in creation of medications that exhibit improved tumor-selective action. Particularly in preclinical and clinical investigations, fusion proteins have shown strong activity and improved treatment outcomes for a number of human cancers. Synergistically combining many proteins into one complex allows the creation of synthetic fusion proteins with enhanced characteristics or new capabilities. Signal transduction pathways are important for onset, development, and spread of cancer. As result, signaling molecules are desirable targets for cancer therapies, and significant effort has been made into developing fusion proteins that would act as inhibitors of these pathways. A wide range of biotechnological and medicinal applications are made possible by fusion of protein domains that improves bioactivities or creates new functional combinations. Such proteins may function as immune effectors cell recruiters to tumors or as decoy receptors for various ligands. In this review article, we have outlined the standard methods for creating fusion proteins and covered the applications of fusion proteins in treatment of cancer. This article also highlights the role of fusion proteins in targeting the signaling pathways involved in cancer for effective treatment.

P11.59.B HIGH GRADE GLIOMAS IN PATIENTS WITH HISTORY OF EXTRACRANIAL CANCERS, A RETROSPECTIVE MULTICENTRIC STUDY

Abstract BACKGROUND Metastases are most frequent brain cancer, involving 50-60% of all intracranial neoplasm. Dominated origins are lung, breast, colorectal cancers. A progress in diagnostic and treatment strategies significantly improved the life expectancy of patients with extracranial cancers. Patients with neurological symptoms should be recommended to the brain MRI. Rarely silent primary brain cancers are revealed. Metastases are considered as a first option, but brain lesions with contrast enhancement could be misdiagnosed. We more and more often meet with high grade glioma (HGG) in patients experienced with other primary cancer. Aim of our study is evaluated an incidence of concurrent cancers, relations between former cancer staging and malignant primary brain tumor evaluation, and also appreciation of treatment efficiency. MATERIAL AND METHODS Data of all glioma patients treated at the three Czech neuro-oncology centers are collected regularly and prospectively during routine maintenance of a database. This work focuses on adult patients with concurrent history both of extracranial cancers and HGGs who underwent resection and oncotherapy between January 2008 and December 2020. Information on the patients’ clinical condition (Karnofsky score (KS)) was collected along with imaging and histological data on each patient’s tumor and details of their cytogenic alterations. Also regarding former extracranial cancers they have been followed up by oncologic center. We excluded the patients with prostate cancer. RESULTS The analysis included 48 patients aged between 44 and 79 years. The median age was 65.3 years. The group contained more women (35/48) than men (13/48). Thirty one patients had a history of breast carcinoma, nine of renal carcinomas and eight of colorectal carcinomas. Following the diagnosis of carcinoma, forty four patients received oncotherapy and four had no adjuvant therapy. Surgery of brain tumors has always revealed HGGs, IDH wild-type. Following the diagnosis HGG thirty patients underwent chemoradiotherapy, thirteen had palliative radiotherapy and five had no oncotherapy. The average time from the diagnosis of extracranial cancer to that of GBM was 4 years. The OS was 11.4 months (range 3-29 months). All the patients succumbed to GBM progression. CONCLUSION Limited number of these patients has been selected. Prognosis was depended on staging of extracranial cancer and performance status. If these patients would be able to pass standard oncologic treatment of primary HGG, they did not find survival distinctions to compare with no extracranial cancer history patients. For right treatment strategy it is mandatory to eliminate misdiagnose of brain metastases and primary malignant brain tumors. This research was funded and supported by Ministry of Health of the Czech Republic (grant NU21-03-00195, NU20-03-00148)

P172 A RARE CASE OF PLATINUM CARDIOTOXICITY: CASE REPORT

Abstract Background The chemotherapy regime containing the Carboplatin–Gemcitabine combination is frequently used for improving outcomes in patients affected by metastatic breast cancer. Platinum compounds were included in the recent ESC Guidelines on cardio–oncology as potential agents which may lead to myocardial infarction, thrombosis and, rarely, heart failure. In this instance it is essential for a strict cardiological follow–up to be carried out during and after treatment. Case report: We present a clinical case report of a 38–year–old woman who was receiving standard oncology treatment for stage IV breast adenocarcinoma. The patient underwent chemotherapy cycles containing the Carboplatin–Gemcitabine combination, with a good response to treatment. It came to our attention for severe dyspnoea, which arose several days before, not compatible with her oncological situation. Transthoracic echocardiography showed severe left ventricular dysfunction (EF 25%; GLS – 9.2%; NT–proBNP 10000 pg/mL), which was not present during earlier tests, and circumferential pericardial effusions, mainly localised along the free wall of the right ventricle, non–haemodynamically significant. Lung ultrasound also showed the presence of pulmonary congestion and bilateral pleural effusions. In the circumstances, she was admitted to the Cardiac Intensive Care Unit for continuation of diagnostic treatment. She then received endo–venous diuretic treatment and haemodynamically supported with Noradrenaline and inotropic agents. A cycle of Levosimendan was performed with an excellent response. Once haemodynamic compensation was re–established, the patient underwent a cardiac CMR which excluded cardiomyopathies and myocarditis and a coronarography was performed which showed no significant lesions in the coronary arteries. After 18 days of hospitalisation in our department, the patient showed an improvement in EF (EF 38%, GLS –12.5%, NT–proBNP 2000 pg/mL), and then she was referred to the oncologist for immunological treatment. Conclusions The diagnosis of cardiotoxicity may not be straightforward due to the aspecificity of the symptoms, its silent progression or because of several comorbidities. Moreover, cardiac damage from chemotherapy is considered reversible if identified early. Treatment is based on the withdrawal of therapy and treatment of symptoms, given that these may be different and unpredictable.

Abstract LB358: Efficacy of a functional precision medicine approach in relapsed/refractory pediatric cancer patients: results from a prospective clinical study

Abstract Personalized medicine often serves as the first salvage therapy strategy when standard oncology treatments fail. However, most precision oncology approaches rely on molecular profiling which, unfortunately, provides therapeutic options for less than 10% of cancer patients. Functional precision medicine (FPM) complements molecular profiling by combining it with rapid, high-throughput drug testing on live patient cells to identify promising treatment options. In this study, we investigated the efficacy of FPM in the management of pediatric patients with recurrent and/or refractory cancers. We enrolled 25 pediatric/young adult patients with refractory solid or liquid cancers in this clinical trial (number NCT03860376). Enrolled patients represented the breadth of cancer indications generally presenting in pediatric patients: acute lymphoblastic leukemia (3 patients), acute myeloid leukemia (3 patients), astrocytoma (1 patient), ependymoma (1 patient), Ewing’s sarcoma (4 patients), glioblastoma (1 patient), malignant rhabdoid tumor (1 patient), medulloblastoma (1 patient), neuroblastoma (1 patient), osteosarcoma (4 patients), rhabdomyosarcoma (4 patients) and Wilms’ tumor (1 patient). We used a functional ex vivo drug sensitivity test (DST) panel encompassing 40 formulary drugs frequently used at Nicklaus Children’s Hospital and 47 non-formulary drugs approved by FDA for cancer treatment, as well as drugs from phase III and IV clinical trials. Drug sensitivity scores (DSS) were calculated for each drug based on cancer cells’ responses. DST results were then combined with results from targeted mutation profiles to match actionable mutations with selective targeted therapies. FPM and molecular data were prospectively generated and treatment recommendations were provided to an FPM Molecular Tumor Board (MTB) of clinicians. In total, 19 of 25 patients (76%) had complete functional and molecular profiling data provided to the MTB to support clinical decision-making. Six patients had their subsequent treatment guided by FPM recommendations, of which 83% (five of six patients) demonstrated greater than 1.3x increased progression-free survival compared to their previous therapy. Interestingly, hierarchical clustering analysis of DST results shows that patients with the same subtype of cancer do not cluster together, and no cancer subtype is differentially represented in either high-level cluster, suggesting the importance of functional profiling to provide deeper insight into individual patient pharmacological response. This FPM study is the first pediatric cancer study to enroll both solid and hematologic cancers regardless of tumor type, and the first FPM study in the United States to generate prospective treatment data on pediatric oncology patients. We illustrate the feasibility and efficacy of FPM to meet the needs of cancer patients with both liquid and solid tumors, especially for high-risk populations such as pediatric cancer patients. Citation Format: Arlet Maria Acanda de la Rocha, Maggie Fader, Ebony R. Coats, Joseph Dunn, Leat Perez, Carolina Velasquez, Jeanette Galano, Cima Saghira, Ileana Sotto, Yana Vorontsova, Ziad Khatib, Haneen Abdella, Cristina M. Andrade-Feraud, Alexa Jacome, Victoria Reis, Lilliam Rimblas, Nicole Tomas, Paula S. Espinal, Noah Berlow, Tomás R. Guilarte, Jennifer McCafferty-Fernandez, Daria Salyakina, Diana J. Azzam. Efficacy of a functional precision medicine approach in relapsed/refractory pediatric cancer patients: results from a prospective clinical study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB358.

Frailty and treatment decisions in older patients with vulvar cancer: A single-center cohort study

IntroductionVulvar cancer is a disease that mainly affects older women. Frailty is an important predictor of outcomes and geriatric assessment can help tailor treatment decisions and improve outcomes. This study aims to assess the prevalence of frailty in older women with vulvar cancer, and how it relates to integrated geriatric care and treatment according to the oncological guidelines. Materials and MethodsA single-center cohort study was performed, among patients 70 years and older, who were diagnosed with vulvar cancer at Leiden University Medical Center, between January 2012 and May 2020. Data on geriatric assessment, treatment decision-making and treatment-related outcomes were collected. ResultsOur study included 114 patients. Mean age was 79.7 years, and 52 patients (45.6%) were frail. Of the frail patients, 42.0% were referred to a geriatrician. In eight of these cases, the geriatrician was actively involved in weighing the benefit and harm of standard oncological treatment versus de-escalated treatment. Frailty, higher age, impairment in the somatic domain, cognitive impairment, and functional dependency were associated with referral to a geriatrician and with active involvement of a geriatrician in decision making. In 26 of frail patients (50.0%) oncological treatment was de-escalated. Frailty, higher age, impairment in the somatic domain, cognitive impairment, and functional dependency were associated with de-escalation of treatment. De-escalated treatment did not compromise survival. DiscussionFrailty is prevalent among older women with vulvar cancer and is associated with referral to a geriatrician and de-escalation of oncological treatment. While this reflects that it is deemed important to tailor treatment decision for frail patients, most frail patients are not routinely evaluated by a geriatrician. Further multidisciplinary collaboration and research is necessary to optimize tailored treatment decisions for this patient group.

Predictive and Prognostic Role of Neutrophil to Lymphocyte Ratio in Rectal Cancer: A Case Control Study with Propensity Score Analysis.

Background: Neutrophil to lymphocyte ratio (NLR) is promoted as a marker reflecting the antitumoral inflammatory response. Herein, we aim to assess whether NLR at the time of diagnosis can predict response to neoadjuvant therapy and long-term survival in a matched cohort of rectal cancer patients. Methods: This is a case control study on rectal cancer patients who underwent standard oncological treatment and had NLR sampled at each stage. ROC curve was used to establish the cut off value of NLR at diagnosis. Two groups (high and low NLR) were compared. Kaplan Meier overall and disease-free survival (DFS) analysis was done comparatively between two groups of patients: low and high NLR. Pearson and Log Rank tests were used to establish statistical significance. Propensity score matching (PSM) was performed, and all variables were compared again on the matched subgroups. Results: One hundred patients were included and 54 were compared again after PSM. NLR at diagnosis did not correlate with tumor regression grade (p=0.77). High NLR at diagnosis (NLR 2.58) was not found to be significantly associated with worse overall survival (p=0.096) or DFS (p=0.128). Similar results were achieved after PSM, except when stage III subgroups were compared, where higher NLR was associated with worse DFS (p=0.04), while results for OS were borderline (p=0.05). Conclusions: Overall, a pretherapeutic high NLR ( 2.58) was not found to predict survival or response do neoadjuvant therapy in patients with rectal cancer. However, a higher NLR may be associated with worse outcomes in advanced colorectal cancer.

Feasibility and Safety of a Combined Metabolic Strategy in Glioblastoma Multiforme: A Prospective Case Series.

Background Glioblastoma multiforme (GBM) may be susceptible to metabolic strategies such as fasting and ketogenic diets, which lower blood glucose and elevate ketones. Combining these two strategies may be an ideal approach for sustaining a potentially therapeutic glucose ketone index (GKI). In this prospective case series, we observed whether a combined metabolic strategy was feasible, safe, and capable of sustaining a GKI <6 in patients with GBM. Methods We provided recommendations and guidelines to 10 GBM patients at various stages of tumour progression and treatment that enabled them to complete a 5–7-day fast every 1–2 months combined with a modified ketogenic diet during the intervening weeks. Patients monitored their blood glucose and ketone levels and body weight. Adverse effects were assessed. Results Patients completed a mean of 161 ± 74 days of the combined metabolic strategy, with 34 ± 18 (21%) days of prolonged fasting (mean fast duration: 6.0 ± 1.4 days) and 127 ± 59 (79%) days on the ketogenic diet. The mean GKI for all 10 patients was 3.22 (1.28 during the fasts, 5.10 during the ketogenic diet). Body weight decreased by 8.4 ± 6.9 kg (11.2% decrease in baseline weight). The most common adverse effects attributed to the fasts and ketogenic diet were fatigue, irritability, and feeling lightheaded. The metabolic strategy did not interfere with standard oncological treatments. Conclusion This is the first study to observe the feasibility and safety of repeated, prolonged fasting combined with a modified ketogenic diet in patients with GBM. Using minimal support, patients maintained the combined metabolic strategy for 5–6 months while sustaining a potentially therapeutic mean GKI of 3.22. Weight loss was considerable. Adverse effects attributed to the metabolic strategy were mild, and it did not interfere with standard oncological treatments. Study Registration: This study is registered on the Australia New Zealand Clinical Trials Registry, number ACTRN12620001310954. The study was registered on 4 December 2020.

Integration of Specialized Palliative Care with Oncological Treatment in Patients with Advanced Pancreatic Cancer.

Introduction:The incidence of pancreatic cancer is around 5 in 100,000, and the 5-year survival is poor. Pancreatic cancer patients have a high disease-specific burden of symptoms, and palliative chemotherapy has varying side effects. The American Society of Clinical Oncology (ASCO) suggests integrating specialized palliative care (SPC) with standard oncological treatment for pancreatic cancer patients at stage ≥III. This study investigated the effects of enrollment into SPC >30 days before death.Materials and Methods:This retrospective study included 170 patients with histopathologically verified pancreatic adenocarcinoma who received palliative chemotherapy at Skåne University Hospital and died between February 1, 2015, and December 31, 2017.Results:Of the 170 patients, 151 were enrolled within the SPC unit; 97 of them for >30 days before death (group A). The remainder (group B) received SPC for ≤30 days before death (n = 54) or not at all (n = 19). Patients in groups A and B lived a median of 73 and 44 days, respectively, after the last palliative chemotherapy treatment (p < 0.001), but did not differ in terms of median overall survival (11.2 months vs. 10.9 months). Death in the hospital occurred in 84% of patients never admitted to SPC and 2% of patients ever admitted to SPC.Conclusion:Enrollment in SPC for longer than 30 days may lower the risk of receiving futile palliative chemotherapy at the end of life, compared with patients enrolled in SPC for 30 days or less before death. Enrollment in SPC lowers the risk of dying in a hospital.

High Intensity Aerobic exercise training and Immune cell Mobilization in patients with lung cancer (HI AIM)\u2014a randomized controlled trial

BackgroundThe increasing role of exercise training in cancer care is built on evidence that exercise can reduce side effects of treatment, improve physical functioning and quality of life. We and others have shown in mouse tumor models, that exercise leads to an adrenalin-mediated increased influx of T and NK cells into the tumor, altering the tumor microenvironment (TME) and leading to reduced tumor growth. These data suggest that exercise could improve immune responses against cancer cells by increase immune cell infiltration to the tumor and potentially having an impact on disease progression. Additionally, there are data to suggest that infiltration of T and NK cells into the TME is correlates with response to immune checkpoint inhibitors in patients. We have therefore initiated the clinical trial HI AIM, to investigate if high intensity exercise can mobilize and increase infiltration of immune cells in the TME in patients with lung cancer.MethodsHI AIM (NCT04263467) is a randomized controlled trial (70 patients, 1:1) for patients with non-small cell lung cancer. Patients in the treatment arm, receive an exercise-intervention consisting of supervised and group-based exercise training, comprising primarily intermediate to high intensity interval training three times per week over 6 weeks. All patients will also receive standard oncological treatments; checkpoint inhibitors, checkpoint inhibitors combined with chemotherapy or oncological surveillance. Blood samples and biopsies (ultrasound guided), harvested before, during and after the 6-week training program, will form basis for immunological measurements of an array of immune cells and markers. Primary outcome is circulating NK cells. Secondary outcome is other circulating immune cells, infiltration of immune cells in tumor, inflammatory markers, aerobic capacity measured by VO2 max test, physical activity levels and quality of life measured by questionnaires, and clinical outcomes.DiscussionTo our knowledge, HI AIM is the first project to combine supervised and monitored exercise in patients with lung cancer, with rigorous analyses of immune and cancer cell markers over the course of the trial. Data from the trial can potentially support exercise as a tool to mobilize cells of the immune system, which in turn could potentiate the effect of immunotherapy.Trial registrationThe study was prospectively registered at ClinicalTrials.gov on February 10th 2020, ID: NCT04263467. https://clinicaltrials.gov/ct2/show/NCT04263467

Adolescent Medical Decisionmaking Rights: Reconciling Medicine and Law.

Dennis Lindberg came into his aunt's care when he was in the 4th grade because his parents struggled with drug addiction and could not provide for him. At thirteen, he was baptized in his aunt's faith as a Jehovah's Witness. Just days after he turned fourteen, on November 6, he was diagnosed with acute lymphoblastic leukemia.The prognosis was that Dennis had a 75% chance of cure with standard oncology treatment. Consistent with the requirements of his new faith, however, Dennis told his doctors, "I do not want to be treated if the requirement is that I would have to take a blood transfusion." His aunt, whose custodial rights seem not to have included medical decisionmaking, was adamant that "[t]his is Dennis's decision."The hospital social worker assigned to Dennis's case assured his aunt that "having just turned 14, [he] could be considered mature enough to make his own decisions." But hospital psychologists declined to evaluate Dennis's maturity because they did "not have the tools for such an assessment." Established hospital policy described the failure to provide a minor with necessary, life-saving care as medical neglect. Hospital ethicists advised that Dennis's autonomy interests were outweighed by the benefits associated with treatment. And, standard oncology practice norms are that doctors should push back against minors' lifesaving treatment refusals. Still, Dennis's doctor agreed with his social worker and aunt, saying, "We owe respect to a 14-year-old[.]" In this view, he was supported by colleagues on staff and by hospital counsel.A county judge got the case only at the eleventh hour, on an emergency motion filed by Dennis's parents and Child Protective Services for a declaration of dependency and to compel the necessary transfusion. Although Dennis was degrading rapidly, his doctor testified that if a transfusion were ordered that day, Dennis still had a 70% chance of survival. The judge had no background in the applicable law and no time to research the issues; nevertheless, he denied the motion concluding, "It is time to do what Dennis has decided." "Seven hours later, at 6 p.m., on Nov. 28, Dennis died."1.

Trends and guideline-related changes in provision of palliative care in older women with gynecologic malignancies

Objectives: To determine if the rate of palliative care consultation (PCC) in older women with gynecologic malignancies increased after the publication of the American Society of Clinical Oncology guidelines in 2012. Additionally, to identify factors associated with utilization of palliative care. Methods: We included women ≥ 66 years with stage III-IV, ovarian, uterine, cervix or vulvar cancer diagnosed in 2011 and 2013 in the linked Surveillance Epidemiology, End Results (SEER)- Medicare database. Patient demographic, cancer, and treatment characteristics were extracted. We evaluated PCC within 365 days of diagnosis (PCC365) and within 56 days of diagnosis (PCC56). We used a multivariable Cox proportional hazard model to compare PCC in 2011 versus 2013. We identified factors associated with PCC in women diagnosed with cancer in 2013 using a univariate and multivariable logistic regression. Results: We identified 2,643 women diagnosed with advanced gynecologic malignancies. 56% of patients had ovarian cancer, 34% uterine cancer, 8% cervical cancer and 3% vulvar cancer. In 2011, 12% of women had a PCC365 versus 14% in 2013. Taking into account multiple factors, women diagnosed in 2013 were more likely to have a PCC365 than women diagnosed in 2011 (adjusted HR 1.36, 95% CI 1.09, 1.71). Women diagnosed with an advanced gynecologic malignancy in 2013 who were Black versus White (adjusted HR 1.72, 95% CI 1.06, 2.78), had a Charlson comorbidity index of 3 versus 0 (adjusted HR 1.81, 95% CI 1.17, 2.80) or stage IV verus stage III cancer (adjusted HR 1.79, 95% CI 1.26, 2.54) were more likely to receive PCC365. Women who received initial cancer treatment with surgery were less likely to receive PCC365 (adjusted HR 0.52, 95% CI 0.35, 0.78). Conclusions: The rate of palliative care in women with advanced gynecologic malignancies increased slightly, although significantly, between 2011 and 2013 but the absolute rate remains low despite changes in recommendations. New innovations are needed to increase concurrent palliative care with standard oncology treatment for woman with advanced gynecologic malignancies.

The Human Fetal and Adult Stem Cell Secretome Can Exert Cardioprotective Paracrine Effects against Cardiotoxicity and Oxidative Stress from Cancer Treatment.

Simple SummaryAnthracyclines, such as doxorubicin (Dox), are an important class of chemotherapeutic drugs. However, their use is hampered by the risk of developing heart failure. The aim of this study was to assess and compare the cardioprotective effects exerted by a set of factors, collectively named secretomes, secreted by either adult or fetal human stem cells. Both secretome formulations were effective in counteracting Dox-induced apoptosis and mitochondrial impairment in cardiomyocytes and cardiac fibroblasts. In vivo experiments in a mouse model of Dox-induced cardiomyopathy (DIC) indicated that early administration of both secretomes during Dox treatment exerted beneficial long-term effects, preserving cardiac function and body mass. These findings suggest that the stem cell secretome could represent a feasible option for future paracrine cardioprotective therapy against Dox-related cardiotoxicity during cancer treatment.Cardiovascular side effects are major shortcomings of cancer treatments causing cardiotoxicity and late-onset cardiomyopathy. While doxorubicin (Dox) has been reported as an effective chemotherapy agent, unspecific impairment in cardiomyocyte mitochondria activity has been documented. We demonstrated that the human fetal amniotic fluid-stem cell (hAFS) secretome, namely the secreted paracrine factors within the hAFS-conditioned medium (hAFS-CM), exerts pro-survival effects on Dox-exposed cardiomyocytes. Here, we provide a detailed comparison of the cardioprotective potential of hAFS-CM over the secretome of mesenchymal stromal cells from adipose tissue (hMSC-CM). hAFS and hMSC were preconditioned under hypoxia to enrich their secretome. The cardioprotective effects of hAFS/hMSC-CM were evaluated on murine neonatal ventricular cardiomyocytes (mNVCM) and on their fibroblast counterpart (mNVFib), and their long-term paracrine effects were investigated in a mouse model of Dox-induced cardiomyopathy. Both secretomes significantly contributed to preserving mitochondrial metabolism within Dox-injured cardiac cells. hAFS-CM and hMSC-CM inhibited body weight loss, improved myocardial function, reduced lipid peroxidation and counteracted the impairment of mitochondrial complex I activity, oxygen consumption, and ATP synthesis induced by Dox. The hAFS and hMSC secretomes can be exploited for inhibiting cardiotoxic detrimental side effects of Dox during cancer therapy, thus ensuring cardioprotection via combinatorial paracrine therapy in association with standard oncological treatments.

Treatment of rectal cancer in the older population

The majority of rectal cancer patients are elderly. Biological age, not chronological age alone, is the main risk factor of postoperative morbidity in this group. Therefore, based on the Comprehensive Geriatric Assessment, we can differentiate three groups of patients: fit, pre-frail and frail. In the fit group, a standard multimodal oncologic treatment can be offered. In the pre-frail group, prerehabilitation should be recommended to improved resilience to surgical stress. In frail patients, a tailored approach should be discussed in a geriatric multidisciplinary team meeting. At present, a whole range of multimodal tailored approaches can be offered to rectal cancer patients. In this group, of much more importance is postoperative functional recovery, including both organ-specific outcomes and the ability to regain independence than currently used outcome indicators. Therefore, as important as cancer staging and tumour biology, it is crucial to understand the health status of an older patient with rectal cancer.