Palliative Therapy Research Articles

Systematic review and recommendations for re-irradiation for intraprostatic radiorecurrent prostate cancer after definitive radiation therapy.

Intraprostatic recurrence (IRR) of prostate cancer after radiation therapy is increasingly identified. Our objective was to review the literature to determine the optimal workup for identifying IRR, the management options, and practical considerations for the delivery of re-irradiation as salvage local therapy. We performed a systematic review of available publications and ongoing studies on the topics of IRR, with a focus on salvage re-irradiation. Work up of biochemically recurrent prostate cancer includes PSMA PET/CT and multiparametric MRI, followed by biopsy to confirm IRR. Management options include continued surveillance, palliative hormonal therapy, and salvage local therapy. Salvage local therapy can be delivered using re-irradiation with low dose rate brachytherapy, high dose rate (HDR) brachytherapy, and stereotactic body radiotherapy (SBRT), as well as non-radiation modalities, such as cryotherapy, high-intensity focused ultrasound, irreversible electroporation and radical prostatectomy. Data demonstrate that HDR brachytherapy and SBRT have similar efficacy compared to the other salvage local therapy modalities, while having more favorable side effect profiles. Recommendations for radiation therapy planning and delivery using HDR and SBRT based on the available literature are discussed. Salvage re-irradiation is safe and effective and should be considered in patients with IRR.

Impact of Facility Volume on Overall Survival in Patients With Head and Neck Cancer Undergoing Palliative Treatment.

Treatment at high-volume facilities (HVF) has been associated with improved prognosis of HNC patients undergoing curative treatment. Whether this systemic factor influences survival outcomes of patients with HNC undergoing palliative treatment is unknown. To investigate the impact of palliative treatment facility volume on overall survival (OS) in patients with head and neck cancer (HNC). The 2004 to 2018 National Cancer Database was queried retrospectively for patients with HNC undergoing palliative treatment. Patients were stratified based on treatment facility volume percentile. Multivariable binary logistic and Cox proportional hazards regression models were implemented. Of 8682 patients included, 1661 (19.1%) underwent palliative therapy at facilities with volume ≥80th percentile. Among 972 facilities included, 643 (66.2%), 182 (18.7%), 85 (8.8%), 44 (4.5%), and 18 (1.9%) had volume <20th, 20-40th, 40-60th, 60-80th, and ≥80th percentiles, respectively. 5-year OS rates of patients undergoing palliative therapy at facilities with volume <20th, 20-40th, 40-60th, 60-80th, and ≥80th percentile was 11%, 13%, 11%, 14%, and 23%, respectively (P < .001). Facility volume ≥80th percentile was associated with higher 5-year OS on multivariable Cox regression (aHR 0.34, 95% CI 0.16-0.69, P < .001). Surgical treatment (aOR 1.34, 95% CI 1.07-1.68, P = .012) was associated with undergoing treatment at facilities with volume ≥80th percentile. Undergoing palliative treatment at HVFs is associated with higher OS in HNC. The survival benefit derived from high facility volume should be carefully considered in the context of other patient and facility characteristics in end-of-life management, with specific emphasis on patient-directed goals of care.

Clinical features and prognosis of parotid metastasis of breast cancer: retrospective analysis of 57 cases.

Parotid gland metastases originating from breast origin are extremely rare, with their clinical presentation, therapeutic approaches, and prognostic indicators remaining to be elucidate. A comprehensive retrospective review was conducted, analyzing the clinical characteristics and prognostic factors of 57 patients diagnosed with parotid metastasis of breast cancer in the existing literature. Notably, our study included two unique cases of patients who developed contralateral and ipsilateral parotid metastases, occurring 5 years and 32 years respectively after primary surgery. This analysis aimed to provide a deeper understanding of the disease presentation and identify potential prognostic indicators. The primary clinical manifestation presented in breast cancer patients with parotid metastases was painless masses in the parotid glands, synchronously or metachronously occurred with primary breast tumors. The predominant pathological subtype among these patients was invasive ductal carcinoma. Out of the 57 patients studied, 24 (42.1%) exhibited metastases solely in the ipsilateral parotid gland, while 18 cases (31.6%) involved either the contralateral or bilateral parotid gland. Patients may solely exhibit metastasis in the parotid gland, or they may present with concurrent multiple metastases in other organs. Patients who suffered from parotid metastases, either merely or accompanied with bone-only metastasis, exhibited significantly longer overall survival (OS) rates compared to those who had concomitant metastases in other organs (1.23 ± 0.26 years vs 4.46 ± 0.77 years, P=0.046). While no statistically significant differences in OS were observed among patients presenting with metastases in the ipsilateral, contralateral, or bilateral parotid glands, a notable variance could be discerned from the Kaplan-Meier curve analysis. Additionally, no significant difference in survival was exhibited between patients with different interval of progression from primary breast sites to initial diagnosis of parotid metastases (uDF), nor for patients who were treated with surgery or palliative therapy. Parotid metastasis, a rare and distinctive form of breast cancer metastasis, demands particular scrutiny in patients exhibiting metastasis to multiple organs or contralateral or bilateral parotid glands.

Real-World Implementation of Simulation-Free Radiation Therapy (SFRT-1000): A Propensity Score-Matched Analysis of 1000 Consecutive Palliative Courses Delivered in Routine Care.

The feasibility of simulation-free radiation therapy (SFRT) has been demonstrated but information regarding its routine care impact and scalability is lacking. In this single-institution, retrospective cohort study, all patients receiving palliative radiation therapy at an Australian tertiary cancer center were eligible for consideration of SFRT unless mask immobilization, a stereotactic technique, or a definitive dose was indicated. Coprimary endpoints were SFRT utilization, impact on consultation-to-RT time, and on-couch treatment duration. Timing metrics were compared with a contemporary local cohort that received simulation-based palliative radiation therapy using unadjusted Wilcoxon rank-sum tests and a propensity score-matched regression. Electronic patient-reported outcomes captured 2-week toxicity and pain response. Between April 2018 and February 2024, 2849 palliative radiation courses were delivered, of which 1904 were eligible. Of the 1904 courses, 1000 (52.5% SFRT utilization) received SFRT, including 668 using intensity-modulated radiation therapy/volumetric-modulated arc therapy. A total of 788 individual patients received SFRT and the median age was 71 years (IQR, 61-80) with 59% being male and 42% being Eastern Collaborative Oncology Group 2-4. SFRT utilization increased from 41% to 54% between years 2018-2019 and 2022-2024. SFRT reduced median consultation-to-RT time from 7.0 to 5.1 days (P < .0001) corresponding to an adjusted average treatment effect in the treated of -2.1 days (95% CI, -2.8 to -1.3). SFRT increased median on-couch treatment duration from 17.8 to 20.5 minutes (P < .0001; adjusted average treatment effect in the treated 2.6 minutes, 95% CI, 1.3-3.9). Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events grade 3 acute toxicity was 9% and at 4 weeks after RT, patients with moderate/severe pain at baseline (≥5/10) had a mean pain reduction of 3.5 points (7.1-3.6; P < .0001). Using widely available technologies, the SFRT-1000 cohort demonstrates routine care scalability with patient-centered and workflow benefits. SFRT is an attractive new paradigm implementable in most settings following adaptation to local requirements. Thus, SFRT opens new avenues to potentially improve access to palliative RT, which remains a global area of need.

212. CLINICAL RESULTS OF PHOTODYNAMIC THERAPY FOR ESOPHAGEAL CANCER PATIENTS WITH INOPERABLE CONDITION

Abstract Background Although surgical resection is the best way for curing cancer, there has been a certain portion of patients who could not undergo surgery because of various reasons. We experienced 10 cases of photodynamic therapy for esophageal cancer patients (Including one case of carcinoma in-situ) with inoperable conditions, and investigated the feasibility and safety of photodynamic therapy (PDT). Methods Medical records of patients of esophageal cancers who received photodynamic therapies between 2005 and 2022 in our institute were reviewed retrospectively. Survival, complication rates and treatment results were evaluated. Results Average age at the time of treatment was 72.4 (±6.47, ranging 64 to 86) and average follow-up periods were 25.0 (±27.7, ranging 3.8 to 89.8). The average Charlson Comorbidity Index (CCI) were 7.3 (±2.29, ranging 4 to 10). During the follow-up periods, 5 patients died, and only one death was related with the esophageal cancer progression. There was one case of skin reaction and no other complications were appeared. There were no complication related deaths. Complete remission of esophageal cancer showed in 7 patients (70.0%) and partial remission showed in 3 patients (30.0%). Two patients with partial remission showed loco-recurrence. One patient with complete remission had to undergo surgery because of preexisting esophageal stenosis. Conclusion Photodynamic therapy could be an option of palliative therapy for advanced esophageal cancer with reasonable complication rates. Therapeutic application could be considered in early esophageal cancer, especially for patients with poor general condition or refusal of surgery. It was still in debates whether it could substitute the surgical role in early esophageal cancers.

Palliative care in advanced pulmonary fibrosis.

Updated clinical practice guidelines for pulmonary fibrosis recommend early integrated palliative care using a primary palliative approach. Clinicians need to be aware of the various palliative interventions in order to implement guidelines' recommendations. This review provides an update on evidence-based palliative therapies. Literature review indicates early integration of palliative care in pulmonary fibrosis is feasible and meets patient needs. Key components of a primary palliative approach include comprehensive symptoms and needs screening, systematic symptom management using nonpharmacologic interventions, supplemental oxygen and opioids for dyspnea and cough. Patient-centered communication is essential for successful integration of palliative care. Early, iterative advance care planning in clinic to understand patient goals, values and preferences for current and future care, improves patient care and satisfaction. Prioritizing caregiver inclusion in clinics can address their needs. Collaborating with a multidisciplinary allied team facilitates integration of palliative care and supports patients throughout the disease course. Different models of palliative care delivery exist and can be adapted for local use. The use of artificial intelligence algorithms and tools may improve care and continuity. Clinicians must develop competency in palliative care. Organizational and policy support is essential to enable seamless integration of palliative care throughout the care continuum.

Time toxicity among older patients with cancer treated with palliative systemic therapy.

The time toxicity of anticancer therapy, defined as days spent with healthcare contact during treatment, represents a critical but understudied outcome. This study aims to quantify time toxicity among older patients with cancer receiving palliative systemic treatment. All patients aged ≥ 65 years with metastatic cancer receiving cytotoxic chemotherapy, immunotherapy, or targeted therapy at a single center in Mexico were selected from a prospective patient navigation cohort. Patients completed a baseline assessment, including the G8 screening and quality of life measures. Physical healthcare contact days within the first 6months were extracted from medical records and divided by days alive during the same period. Beta regression models were used to identify predictors of time toxicity. We identified 158 older patients (median age 71 years); 86% received cytotoxic chemotherapy. Seventy-three percent had an impaired G8 score and were considered vulnerable/frail. Six-month overall survival was 74%. Within the first 6months, patients spent a mean of 21% (95% confidence interval (CI) 19-23%) of days with healthcare contact. Concurrent radiotherapy (odds ratio (OR) 1.55; 95%CI 1.21-1.97), cytotoxic chemotherapy versus targeted therapy (OR 1.64; 95%CI 1.13-2.37), and an impaired G8 (OR 1.27; 95%CI 1.01-1.60) were associated with increased time toxicity. Older adults with metastatic cancer spend 1 in 5days with healthcare contact during treatment, with a higher burden of time toxicity for patients receiving radiotherapy or cytotoxic chemotherapy and those with potential frailty. These findings underscore the importance of informing patients about their expected healthcare contact days within the context of a limited life expectancy.

Elaborating the knowledge structure and emerging research trends of physical activity for multiple sclerosis: A bibliometric analysis from 1994 to 2023

BackgroundMultiple sclerosis is a common inflammatory neurological disease among young adults and is the tenth leading cause of the global burden of disease. Existing common treatments such as pharmacological and palliative therapies do not control the neurodegenerative process or cure multiple sclerosis. Numerous epidemiological surveys, randomised controlled trials, and systematic reviews with meta-analyses support the effects of physical activity on health-related outcomes among patients with multiple sclerosis. Moreover, bibliometric analysis can provide a broad evidence synthesis beyond systematic reviews and meta-analyses, allowing researchers and other stakeholders to obtain a one-stop overview of this research field. Therefore, this bibliometric analysis aims to provide insight into the knowledge structure of the field of physical activity for multiple sclerosis over the past three decades, and to predict emerging research trends. MethodsThis study strictly complied with step-by-step guidelines of bibliometric analysis, combining performance analysis and science mapping. Four indexes from the Web of Science Core Collection were selected as data sources, and articles and review articles in the field of physical activity for multiple sclerosis from 1994 to 2023 were included in this analysis. Mircrosoft Excel, RStudio, VOSviewer 1.6.20, and CiteSpace 6.3.R1 (64-bit) Advanced were used to perform performance analysis and science mapping. ResultsOver the past three decades, this field published a total of 1,271 documents, with the scientific output showing a rapid upward trend over the past two decades. Robbert W Motl was the most prolific author in this field, with a total of 300 publications. The USA contributed nearly half of the publications in this field (549 documents), and the University of Illinois System was the institution with the highest number of publications (222 documents). Multiple Sclerosis and Related Disorders was the journal that published the highest number of documents in this field (117 documents), while more than a third of this field's publications were included in the category: Clinical Neurology (438 documents). The Reference co-citation analysis identified three main research trends, including shifts in research methodology, changes in health outcomes in randomised controlled trials, and shifts in different types of physical activity interventions. Combining the results from reference co-citation analysis and citation burst analysis, the combination of behaviour change technique and telerehabilitation may be the emerging research trend. ConclusionThis bibliometric analysis identifies rapid growth in the field of physical activity for multiple sclerosis over the past two decades. Moreover, the combination of performance analysis and science mapping provides insight into knowledge structure in this field and informed future research trends for researchers and the relevant stakeholders.

Biomarker-stratified first-line treatment of right-sided metastatic colon cancer with interdisciplinary collaboration in the IVOPAK II trial.

Patients with right-sided metastatic colon carcinoma have a significantly worse prognosis than those with left-sided colorectal cancer (CRC), regardless of treatment. The aim of the prospective IVOPAK II study was to implement an interdisciplinary guideline-conform personalized CRC palliative therapy of metastatic colorectal carcinoma and to improve the overall survival (OS) by multidisciplinary approach via secondary metastatic resection. We present the efficacy data of first-line treatment and the benefit of interdisciplinary collaboration of right-sided metastatic colon carcinoma patients: n = 25. RAS mutation: n = 20 (80%): received systemic first-line treatment: FOLFIRI plus bevacizumab. All-RAS-wildtype: n = 5 (20%): received systemic first-line treatment: FOLFIRI plus cetuximab. Last date evaluation: 31 January 2024. Median age: 59.6 years (range 42-71), men/women: 14/11. Eastern Cooperative Oncology Group (ECOG) index: 0/1/2 : 11/10/4. Evaluable for response: n = 25. Complete response: n = 0, partial response: n = 14 (56%), stable disease: n = 8 (32%), progressive disease: n = 3 (12%), early tumor shrinkage: n = 13 (52%), estimates progression-free survival: 13 months (95% CI 8-17 months), estimated OS: 48 months (95% CI 25-71 months), median follow-up: 26 months (1-61 months), no evidence of disease: n = 4 (16%). A chemotherapy doublette regimen with FOLFIRI plus a biological as first-line treatment shows promising efficacy and secondary metastatic resection after interdisciplinary discussion was associated with a survival benefit in right-sided metastatic colon carcinoma.

BRAF and MEK inhibitor targeted therapy in papillary craniopharyngiomas: a cohort study.

Targeted therapy (TT) with BRAF/MEK inhibitors has emerged as a potential treatment in papillary craniopharyngiomas (PCPs). However, standardized data on large cohorts are lacking. Our study aimed to assess real-life efficacy and safety of BRAF/MEK inhibition in patients with PCPs. Retrospective French multicenter study involving BRAF V600E-mutated PCP patients, treated with BRAF/MEK inhibitor combination dabrafenib and trametinib, from April 2019 to July 2023. Objective response and clinical and safety outcomes were assessed after 3 months and at the last available follow-up during TT. Sixteen patients (8 females, mean age 50.5 ± 15.75 years), receiving either neoadjuvant therapy (NEO) for non-resectable tumors (n = 6), post-surgical adjuvant therapy (ADJ; n = 8), or palliative therapy (PAL) following failure of multimodal treatment (n = 2), were included.At the last follow-up (mean 7.6 ± 5.3 months), 12 patients showed subtotal response, 3 exhibited partial response, and 1 maintained stable disease. Mean volume reduction was 88.9 ± 4.4%, 73.3 ± 23.4%, and 91.8 ± 4.3% in the NEO, ADJ, and PAL groups, respectively.Targeted therapy resolved headaches in 5/5 patients and visual impairment in 6/9; 2/3 patients had improved neurological symptoms, 1/4 presented weight loss, and 2/14 recovered endocrine function.Targeted therapy was well-tolerated in 62.5% of cases; adverse events led to treatment discontinuation in 5 patients and definitive discontinuation in 3 cases. In this study, 94% of patients showed partial response or better to TT. Adverse events were acceptable. Further research is needed to establish standardized protocols; however, these results advocate for a NEO approach in invasive PCPs.

Insights from explainable AI in oesophageal cancer team decisions

BackgroundClinician-led quality control into oncological decision-making is crucial for optimising patient care. Explainable artificial intelligence (XAI) techniques provide data-driven approaches to unravel how clinical variables influence this decision-making. We applied global XAI techniques to examine the impact of key clinical decision-drivers when mapped by a machine learning (ML) model, on the likelihood of receiving different oesophageal cancer (OC) treatment modalities by the multidisciplinary team (MDT). MethodsRetrospective analysis of 893 OC patients managed between 2010 and 2022 at our tertiary unit, used a random forests (RF) classifier to predict four possible treatment pathways as determined by the MDT: neoadjuvant chemotherapy followed by surgery (NACT + S), neoadjuvant chemoradiotherapy followed by surgery (NACRT + S), surgery-alone, and palliative management. Variable importance and partial dependence (PD) analyses then examined the influence of targeted high-ranking clinical variables within the ML model on treatment decisions as a surrogate model of the MDT decision-making dynamic. ResultsAmongst guideline-variables known to determine treatments, such as Tumour-Node-Metastasis (TNM) staging, age also proved highly important to the RF model (16.1 % of total importance) on variable importance analysis. PD subsequently revealed that predicted probabilities for all treatment modalities change significantly after 75 years (p < 0.001). Likelihood of surgery-alone and palliative therapies increased for patients aged 75–85yrs but lowered for NACT/NACRT. Performance status divided patients into two clusters which influenced all predicted outcomes in conjunction with age. ConclusionXAI techniques delineate the relationship between clinical factors and OC treatment decisions. These techniques identify advanced age as heavily influencing decisions based on our model with a greater role in patients with specific tumour characteristics. This study methodology provides the means for exploring conscious/subconscious bias and interrogating inconsistencies in team-based decision-making within the era of AI-driven decision support.

Phase III randomized trial comparing palliative systemic therapy to best supportive care in advanced esophageal/GEJ cancer.

No study has unequivocally proven that chemotherapy prolongs overall survival (OS) in advanced esophageal cancer. We conducted a Phase III randomized study in first-line advanced unresectable/metastatic esophageal/GEJ cancer. Patients aged 18-70 years, with performance status 0-2, were randomized to best supportive care (BSC) alone, or BSC with weekly paclitaxel 80 mg/m2. BSC comprised, as indicated, education, counselling, radiation, stenting, feeding tube placement, nutritional supplementation, medications like analgesics, and referral to a support group and palliative care. The primary endpoint was OS; secondary endpoints included progression free survival (PFS), response, toxicity, and QoL. Between May 2016-December 2020, we recruited 281 patients: 143 to chemotherapy and 138 to BSC. Histopathology was squamous in 269 (95.7%) patients. Median number of paclitaxel doses was 12 (IQR, 7-23). Median OS was 4.2 months (95% CI, 3.42-5.32) in BSC, and 9.2 months (95% CI, 8.02-10.48) in chemotherapy; HR, 0.49 (95% CI, 0.39-0.64); p < .001. As compared to BSC, chemotherapy increased response (2.9% to 39%), median PFS (2.1 to 4.2 months), 1-year OS (11% to 32%), 2-year OS (0 to 9%), median dysphagia-free survival (2.9 to 14.8 months), and global and esophagus-specific QoL, without significantly increasing all-grade or grade ≥3 toxicities. Using ESMO clinical benefit scale and ASCO Value Framework, palliative chemotherapy scored as having "substantial value." Our study provides the first level 1 evidence that chemotherapy prolongs survival in advanced esophageal/GEJ carcinoma. BSC alone is no longer appropriate. Weekly paclitaxel is an attractive option, especially in LMICs with limited access to immunotherapy.

Abstract Mo092: Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes as an In Vitro Model to Evaluate the Efficacy of a Gene Replacement Therapy for Plakophilin-2- Associated Arrhythmogenic Right Ventricular Cardiomyopathy

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiac disorder characterized by severe arrhythmias and heart dysfunction. Mutations in desmosome gene Plakophilin-2 ( PKP2 ) account for 40% of ARVC cases, with current palliative therapies failing to address the genetic cause. Herein, we generated an in vitro ARVC model using human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) harboring a pathogenic PKP2 variant (c.2146G&gt;C), as a platform to test a PKP2 -gene replacement approach developed at Tenaya Therapeutics for the treatment of PKP2 -associated ARVC patients. Methods: Three isogenic human iPSC lines (wild-type, heterozygous and homozygous PKP2 mutant) were differentiated to iPSC-CM; and monolayers and engineered heart tissues (EHTs) were generated. Gene and protein expression were assessed by RNA-Seq/RT-qPCR, and immunocytochemistry, respectively. Contractility, electrophysiology and calcium handling were measured. A proprietary adeno-associated virus gene therapy (AAV9: PKP2 ) was used to transduce human iPSC-CM, and changes in gene and protein expression, and contractile function were evaluated. Results: A human iPSC-CM beating monolayer was achieved for all three lines. PKP2 expression was depleted in a genotype-dependent manner, and desmosome structure was disrupted in the mutant lines. Functional assessment of human iPSC-CM monolayers showed impaired contractile properties and abnormal electrophysiological and calcium transients in the mutant lines, such as decreased contraction amplitude and prolonged field and action potential duration. Transcriptional analysis revealed changes in desmosome, gap junctions, sarcomere, ion channels, metabolic and apoptosis gene expression. Characterization of EHTs displayed a deficit in contractility, slower action and field potential kinetics and irregular calcium homeostasis in the mutant lines. The administration of AAV9: PKP2 to the mutant lines restored ion channel and desmosome gene and protein expression, and contractile function. Conclusions: Our PKP2 human iPSC-CM disease model recapitulated the main hallmarks of ARVC phenotype. Administration of AAV9: PKP2 restored desmosome protein expression and contractility. This model lays a foundation for the understanding of the underlying molecular pathophysiological mechanisms of PKP2 -ARVC, and the potential for AAV9: PKP2 as a one-time dose to correct the genetic cause of disease in individuals with PKP2 -associated ARVC.

Management considerations and treatment outcomes for newly diagnosed prostate cancer in advanced age patients (≥80 years): real-world data from a single urological center over a 10-year period.

There is ongoing debate regarding prostate cancer (PCa) screening in advanced age males, leading to treatment decisions often based on tumor staging and life expectancy. A critical gap in clinical evidence and tailored guidelines for the advanced age with PCa persists. This study aims to compare survival outcomes of various treatment approaches in this demographic. We analyzed data from a large urological center for advanced age patients suspected of having PCa between 2012 and 2022. We collected clinical and pathological characteristics and evaluated treatment modalities, including palliative therapy and definitive therapy. Propensity score matching (PSM) analysis was implemented to reduce bias between treatment modalities. Kaplan-Meier and multivariate Cox proportional hazard regression analyses were conducted to evaluate progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Out of 4,333 suspected patients, 376 individuals aged 80 years and older underwent prostate biopsy. The overall detection rate of PCa was 78.7%, with a high prevalence of high-grade tumors [International Society of Urological Pathology (ISUP) grade ≥2]. Most patients (86.5%) received palliative therapy, while 13.5% underwent definitive therapy. Patients in the definitive therapy group had lower prostate-specific antigen (PSA) values, lower tumor stage, and Charlson Comorbidity Index (CCI), longer life expectancy, and a higher Geriatric 8 (G8) score compared to the palliative therapy group. The median OS for the entire cohort was 72.0 months, with 70.0 months for palliative therapy and 96.0 months for definitive therapy. Multivariable analyses identified lymphatic and bone metastasis, as well as definitive therapy, as independent prognostic factors for PFS, CSS, and OS. Advanced age patients, although a small group, have distinct characteristics, including higher PSA levels, positive biopsy rates, and pathological grading and staging. In medically fit elderly patients, especially those with localized PCa and a life expectancy of ≥5 years, definitive therapy could improve survival outcomes.

Effectiveness of palliative photodynamic therapy for unresectable biliary cancer. Systematic review and meta-analysis

A systematic review and meta-analysis was aimed to assess the effectiveness of palliative photodynamic therapy for unresectable malignant tumors of the biliary system in order to justify the feasibility of including photodynamic therapy (PDT) in the complex treatment of this category of patients. Publications in the databases PubMed Central, the bibliographic database of scientifi citations of the RSCI, and the Cochrane library were considered. Heterogeneity was assessed graphically using forest plots and statistically using tau2 and I2 statistics. A meta-analysis of 5-year survival revealed a statistically signifiantly longer pooled estimate of the survival period in groups where PDT was used – 339±161 days (95% CI 25-710; p &lt; 0.001) compared to groups where PDT was not used – 83±16 days (95% CI 33-100; p &lt; 0.001). Heterogeneity among studies was found to be statistically insignifiant (I2 = 29%, p = 0.23). A meta-analysis of the risk difference for adverse events revealed a statistically signifiantly lower risk (-0.2306; 95% CI -0.3917-0.0696; p = 0.005) of adverse events after PDT compared with the comparison group. Heterogeneity among studies was found to be statistically insignifiant (I2 = 0%, p = 0.35). There were no signifiant publication biases in either meta-analysis. The presented meta-analysis demonstrated that PDT may be the method of choice in the palliative complex treatment of patients with unresectable cholangicarcinomas, increasing the ˝ve-year survival of patients along with the absence of increased risks of postoperative complications in comparison with other methods of palliative surgical treatment.

The Predictive Role of Metabolic Volume Segmentation Compared to Semiquantitative PET Parameters in Diagnosis of LVAD Infection using [18F]FDG Imaging

PurposeLeft ventricular assisting device (LVAD) is a vital mechanical circulatory assist device for patients with end-stage heart disease, serving as either a bridge to transplantation or palliative destination therapy. Yet device infection represents a major lethal complication, warranting a multi-step, complex therapy approach including an urgent device exchange or heart transplantation. Still, timely diagnosis of site and extent of VAD-specific infection for a proper therapy planning poses challenges in regular clinical care. This single-center, retrospective study aimed to evaluate the impact of volumetric PET parameters with different thresholding compared to semiquantitative PET parameters for accurate diagnosis of VAD-specific infection.ProceduresSeventeen patients (1 female, 16 males; mean age 57 ± 11 years) underwent [18F]FDG imaging for suspected VAD-specific infection between April 2013 and October 2023. Various metabolic and volumetric PET parameters with different thresholding were collected for specific LVAD components including driveline entry point, subcutaneous driveline, pump pocket, inner cannula and outflow tract. Microbiology and clinical follow-up were used as the final diagnosis standard.ResultsNine of eleven patients with VAD-specific infection underwent urgent heart transplantation, and one had a surgical revision of LVAD. Two patients had non-VAD specific infections, and two had non-VAD related infections. Metabolic burden determination using a fixed absolute threshold provided the best outcome compared to relative thresholding or other metabolic SUV parameters. The total metabolic tumor volume (MTV) cutoff value was 9.3 cm3, and the corresponding sensitivity, specificity, accuracy, and AUC were 90.0%, 71.43%, 82.5%, and 0.814 (95% CI 0.555–0.958), respectively. The total lesion glycolysis (TLG) was 30.6, and the corresponding sensitivity, specificity, accuracy, and AUC were 90.0%, 71.4%, 82.5%, and 0.829 (95% CI 0.571–0.964), respectively.ConclusionsVolumetric PET parameters with fixed absolute thresholding appear to be a valuable auxiliary tool in the evaluation of [18F]FDG imaging to enhance the diagnostic accuracy of VAD-specific infection.

Ethical and legal aspects of end of life in dialysispatients: an Italian point of view.

In the Western world, thanks to continuous progress in the medical field, and to changes in society,the concept of death seems to be increasingly replaced by that of "keeping alive at all costs". Thus also dialysis, a life-sustainingtreatment for patients suffering from kidney failure, in some cases can no longer be seen as a treatment aimed at prolonging life, but as a treatmentto temporarily avert death. In fact, the literature highlights that dialysis is not always associated with greater lifeexpectancy and better quality of life for fragile patients with kidney failure. This point-of-viewpaperdiscusses legal and ethical principles of respect for patient autonomy (beneficence, non-maleficence, justice and professional integrity) inherent in the choice to suspend or tonot start dialysis treatment, while following apathway ofconservative and/or palliative therapy.

Systemic Treatment Strategies and Outcomes of Patients With Synchronous Peritoneal Metastases of Gastric Origin: A Nationwide Population-Based Study.

Palliative systemic treatment is currently standard of care for metastatic gastric cancer. However, patients with peritoneal metastases of gastric origin are often underrepresented in clinical studies due to unmeasurable radiologic disease. This study describes the systemic treatment strategies and outcomes in patients with peritoneal metastases in a nationwide real-world setting. Patients with gastric adenocarcinoma and synchronous peritoneal metastases (with or without other metastases) diagnosed in the Netherlands between 2015 and 2020 were identified from the nationwide Netherlands Cancer Registry. Median overall survival (OS) and time-to-treatment failure were determined and multivariable Cox regression analyses were used to compare treatment groups, corrected for relevant tumor and patient characteristics. In total, 1,972 patients were included, of whom 842 (43%) were treated with palliative systemic therapy. The majority received capecitabine + oxaliplatin (CAPOX; 44%), followed by fluorouracil/leucovorin/oxaliplatin (FOLFOX; 19%), and epirubicin + capecitabine + oxaliplatin (EOX; 8%). Of the 99 (45%) patients who received second-line systemic treatment, ramucirumab + paclitaxel were administered most frequently (63%). After adjustment for sex, age, comorbidities, performance status, tumor location, Lauren classification, and the presence of metastases outside of the peritoneum, patients treated with a triplet containing docetaxel and those treated with a regimen containing trastuzumab had a significantly longer OS compared with patients treated with a doublet containing a fluoropyrimidine derivate + oxaliplatin (hazard ratio [HR], 0.69; 95% CI, 0.52-0.91, and HR, 0.68; 95% CI, 0.51-0.91, respectively). Monotherapy was associated with a shorter OS (HR, 2.08, 95% CI, 1.53-2.83). There is substantial heterogeneity in systemic treatment choices in patients with gastric cancer and peritoneal metastases in the Netherlands. In this study, patients treated with triplets containing docetaxel and with trastuzumab-containing regimens survived longer than patients who received doublet therapy. Despite this, median OS for all treatment groups remained below one year.

A Review of the Literature on Episodes of Acute Fentanyl Intoxication in Pediatric Age and Toxicological Applications.

Fentanyl is an opioid with powerful analgesic effects and a high speed of action. Due to its pharmacological properties, this molecule has therapeutic application as an anesthetic in surgery or as palliative therapy for cancer patients. Unfortunately, in recent years, the easy availability of this substance, the low cost and the illegal online market have favored the large-scale diffusion of fentanyl. Fentanyl is available in different forms, including nasal spray, oral patches, soluble capsules, aerosol or the new version of fentanyl mixed with other drugs, making its use very widespread. Subjects of various ages are involved in fentanyl consumption, including minors that have not yet reached adolescence. In this work, we performed a literature review using the search engines PubMed NCBI and SCOPUS regarding episodes of acute fentanyl intoxication occurring in those of a pediatric age using the Mesh Terms "fentanyl" AND "overdose" AND "children". The inclusion criteria were English papers published in the last 10 years regarding the cases of children under the age of 10. We evaluated the most frequent methods of intake and the circumstances of such episodes. In cases of death, we analyzed the autopsy, the toxicological findings and the investigations carried out. The review results show that in this age group (under < 10 y.o. s), it is possible to identify the risk factors for fentanyl intake, such as the presence of this molecule within the family unit due to drug addiction or medical therapy. The results also demonstrate a significant risk of underestimation of this phenomenon, since the molecule is often not investigated through adequate toxicological analysis. These results, therefore, suggest always carrying out toxicological investigations in the case of suspected fentanyl intoxication, both on patients or cadavers. The investigations must always include a urinary screening for opiates, and the request for a second level analysis with molecule dosage in cases of positivity or in cases of strong suspicion for assumption. In cases of intoxication in a family context of drug addiction, it is necessary to investigate the chronicity of the intake through hair analysis and evaluate the possible co-administration of other drugs. In conclusion, we suggest a protocol, applicable both on patients or cadavers, which can be useful for physicians and forensic pathologists in order to promptly identify these cases and allow for the reporting of them to the judicial authorities with the adoption of strict prevention and control measures.

Weekly paclitaxel, carboplatin and cetuximab (PCC) combination followed by nivolumab in platinum-sensitive recurrent and /or metastatic squamous cell carcinoma of head and neck: a retrospective analysis from two institutions in India

Background: First line (1L) TP-Ex-like regimen followed by 2nd-line (2L) immunotherapy represents one of the standards of care in platinum-sensitive recurrent and/or metastatic squamous cell carcinoma of head and neck (R/M SCCHN). We report our experience from 2 tertiary care institutions of India. Methods: This is a retrospective analysis of consecutive patients of platinum-sensitive R/M SCCHN treated with 1L weekly paclitaxel, carboplatin, and cetuximab (PCC) regimen followed by cetuximab maintenance (if non-progressive) or 2L nivolumab or oral metronomic chemotherapy (OMCT) on progression. Overall response rates (ORR), progression-free survival after 1L and 2L (PFS-1 &amp; PFS-2), overall survival (OS), and safety were evaluated. Results: The study included 54 patients; median age 56.5 years; 89% men; 11% had cardiac dysfunction; 13% had renal dysfunction. After 1L PCC, ORR was 59.3%; median PFS-1 was 7.031 months; 61% had progression; 35% were treated with nivolumab and 18% with OMCT. The ORR was 26.3% (nivolumab) and 10% (OMCT). Median PFS-2 was 6.5 months (nivolumab) and 2 months (OMCT). The median OS was 15.01 months (entire cohort), 20.6 months (nivolumab), and 7 months (OMCT). Grade III/IV adverse events on PCC included neutropenia (31.4%), anaemia (35.1%), thrombocytopenia (7.4%), febrile neutropenia (11.1%), and skin reaction (16.6%); no Grade-III/IV treatment-related toxicities on 2L. Conclusions: 1L weekly PCC is an effective regimen for palliative therapy of platinum- sensitive R/MSCCHN with an acceptable toxicity profile. The addition of 2L nivolumab on progression further improves the outcomes.