Long-term outcomes of stereotactic body radiation therapy (SBRT) with fiducial tracking for inoperable stage I non-small cell lung cancer (NSCLC)

BACKGROUND: Stereotactic body radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC) is considered standard of care in the medically inoperable patient population. Multiple methods of SBRT delivery exist including fiducial-based tumor tracking, which allows for smaller treatment margins and avoidance of patient immobilization devices. We explore the long-term clinical outcomes of this novel fiducial-based SBRT method. METHODS: In this single institutional retrospective review, we detail the outcomes of medically inoperable pathologically confirmed stage I NSCLC. Patients were treated with the Cyberknife SBRT system using a planning target volume (PTV) defined as a 5-mm expansion from gross tumor volume (GTV) without creation of an internal target volume (ITV). Dose was delivered in three or five equal fractions of 10 to 20 Gy. Pretreatment and posttreatment pulmonary function test (PFT) changes and evidence of late radiological rib fractures were analyzed for the majority of patients. Actuarial local control, locoregional control, distant control, and overall survival were calculated using the Kaplan-Meier method. RESULTS: Sixty-one patients with a median age of 75 years were available for analysis. The majority (80 %) of patients were deemed to be medically inoperable due to underlying pulmonary dysfunction. Eleven patients (18 %) developed symptomatic pneumothoraces secondary to fiducial placement under CT guidance, which precipitously dropped to 0 % following transition to bronchoscopic fiducial placement. The 2-year rib fracture risk was 21.4 % with a median time to rib fracture of 2.9 years. PFTs averaged over all patients and parameters demonstrated small absolute declines, 5.7 % averaged PFT decline, at approximately 1 year of follow-up, but only the diffusing capacity of lung for carbon monoxide (DL(CO)) demonstrated a statistically significant decline (10.29 vs. 9.01 mL/min/mmHg, p = 0.01). Five-year local control, locoregional control, and overall survival were 87.6, 71.8, and 39.3 %, respectively. CONCLUSIONS: Despite reduced treatment margins and lack of patient immobilization, SBRT with fiducial-based tumor tracking achieves clinically comparable long-term outcomes to other linac-based SBRT approaches

Rationale for Utilization of Hydrogel Rectal Spacers in Dose Escalated SBRT for the Treatment of Unfavorable Risk Prostate Cancer

In this review we outline the current evidence for the use of hydrogel rectal spacers in the treatment paradigm for prostate cancer with external beam radiation therapy. We review their development, summarize clinical evidence, risk of adverse events, best practices for placement, treatment planning considerations and finally we outline a framework and rationale for the utilization of rectal spacers when treating unfavorable risk prostate cancer with dose escalated Stereotactic Body Radiation Therapy (SBRT)

High-risk prostate cancer treated with a stereotactic body radiation therapy boost following pelvic nodal irradiation

PurposeModern literature has demonstrated improvements in long-term biochemical outcomes with the use of prophylactic pelvic nodal irradiation followed by a brachytherapy boost in the management of high-risk prostate cancer. However, this comes at the cost of increased treatment-related toxicity. In this study, we explore the outcomes of the largest cohort to date, which uses a stereotactic body radiation therapy (SBRT) boost following pelvic nodal radiation for exclusively high-risk prostate cancer.Methods and materialsA large institutional database was interrogated to identify all patients with high-risk clinical node-negative prostate cancer treated with conventionally fractionated radiotherapy to the pelvis followed by a robotic SBRT boost to the prostate and seminal vesicles. The boost was uniformly delivered over three fractions. Toxicity was measured using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Oncologic outcomes were assessed using the Kaplan–Meier method. Cox proportional hazard models were created to evaluate associations between pretreatment characteristics and clinical outcomes.ResultsA total of 440 patients with a median age of 71 years were treated, the majority of whom were diagnosed with a grade group 4 or 5 disease. Pelvic nodal irradiation was delivered at a total dose of 4,500 cGy in 25 fractions, followed by a three-fraction SBRT boost. With an early median follow-up of 2.5 years, the crude incidence of grade 2+ genitourinary (GU) and gastrointestinal (GI) toxicity was 13% and 11%, respectively. Multivariate analysis revealed grade 2+ GU toxicity was associated with older age and a higher American Joint Committee on Cancer (AJCC) stage. Multivariate analysis revealed overall survival was associated with patient age and posttreatment prostate-specific antigen (PSA) nadir.ConclusionUtilization of an SBRT boost following pelvic nodal irradiation in the treatment of high-risk prostate cancer is oncologically effective with early follow-up and yields minimal high-grade toxicity. We demonstrate a 5-year freedom from biochemical recurrence (FFBCR) of over 83% with correspondingly limited grade 3+ GU and GI toxicity measured at 3.6% and 1.6%, respectively. Long-term follow-up is required to evaluate oncologic outcomes and late toxicity

High-risk prostate cancer treated with a stereotactic body radiation therapy boost following pelvic nodal irradiation

Purpose Modern literature has demonstrated improvements in long-term biochemical outcomes with the use of prophylactic pelvic nodal irradiation followed by a brachytherapy boost in the management of high-risk prostate cancer. However, this comes at the cost of increased treatment-related toxicity. In this study, we explore the outcomes of the largest cohort to date, which uses a stereotactic body radiation therapy (SBRT) boost following pelvic nodal radiation for exclusively high-risk prostate cancer. Methods and materials A large institutional database was interrogated to identify all patients with high-risk clinical node-negative prostate cancer treated with conventionally fractionated radiotherapy to the pelvis followed by a robotic SBRT boost to the prostate and seminal vesicles. The boost was uniformly delivered over three fractions. Toxicity was measured using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Oncologic outcomes were assessed using the Kaplan–Meier method. Cox proportional hazard models were created to evaluate associations between pretreatment characteristics and clinical outcomes. Results A total of 440 patients with a median age of 71 years were treated, the majority of whom were diagnosed with a grade group 4 or 5 disease. Pelvic nodal irradiation was delivered at a total dose of 4,500 cGy in 25 fractions, followed by a three-fraction SBRT boost. With an early median follow-up of 2.5 years, the crude incidence of grade 2+ genitourinary (GU) and gastrointestinal (GI) toxicity was 13% and 11%, respectively. Multivariate analysis revealed grade 2+ GU toxicity was associated with older age and a higher American Joint Committee on Cancer (AJCC) stage. Multivariate analysis revealed overall survival was associated with patient age and posttreatment prostate-specific antigen (PSA) nadir. Conclusion Utilization of an SBRT boost following pelvic nodal irradiation in the treatment of high-risk prostate cancer is oncologically effective with early follow-up and yields minimal high-grade toxicity. We demonstrate a 5-year freedom from biochemical recurrence (FFBCR) of over 83% with correspondingly limited grade 3+ GU and GI toxicity measured at 3.6% and 1.6%, respectively. Long-term follow-up is required to evaluate oncologic outcomes and late toxicity

Time interval from diagnosis to treatment of brain metastases with stereotactic radiosurgery is not associated with radionecrosis or local failure

IntroductionBrain metastases are the most common intracranial tumor diagnosed in adults. In patients treated with stereotactic radiosurgery, the incidence of post-treatment radionecrosis appears to be rising, which has been attributed to improved patient survival as well as novel systemic treatments. The impacts of concomitant immunotherapy and the interval between diagnosis and treatment on patient outcomes are unclear.MethodsThis single institution, retrospective study consisted of patients who received single or multi-fraction stereotactic radiosurgery for intact brain metastases. Exclusion criteria included neurosurgical resection prior to treatment and treatment of non-malignant histologies or primary central nervous system malignancies. A univariate screen was implemented to determine which factors were associated with radionecrosis. The chi-square test or Fisher’s exact test was used to compare the two groups for categorical variables, and the two-sample t-test or Mann-Whitney test was used for continuous data. Those factors that appeared to be associated with radionecrosis on univariate analyses were included in a multivariable model. Univariable and multivariable Cox proportional hazards models were used to assess potential predictors of time to local failure and time to regional failure.ResultsA total of 107 evaluable patients with a total of 256 individual brain metastases were identified. The majority of metastases were non-small cell lung cancer (58.98%), followed by breast cancer (16.02%). Multivariable analyses demonstrated increased risk of radionecrosis with increasing MRI maximum axial dimension (OR 1.10, p=0.0123) and a history of previous whole brain radiation therapy (OR 3.48, p=0.0243). Receipt of stereotactic radiosurgery with concurrent immunotherapy was associated with a decreased risk of local failure (HR 0.31, p=0.0159). Time interval between diagnostic MRI and first treatment, time interval between CT simulation and first treatment, and concurrent immunotherapy had no impact on incidence of radionecrosis or regional failure.DiscussionAn optimal time interval between diagnosis and treatment for intact brain metastases that minimizes radionecrosis and maximizes local and regional control could not be identified. Concurrent immunotherapy does not appear to increase the risk of radionecrosis and may improve local control. These data further support the safety and synergistic efficacy of stereotactic radiosurgery with concurrent immunotherapy

Prognostic utility of biopsy-based PTEN and ERG status on biochemical progression and overall survival after SBRT for localized prostate cancer

Introduction/backgroundPhosphatase and tensin homolog (PTEN) genomic deletions and transmembrane protease, serine 2/v-ets avian erthyroblastosis virus E26 oncogene homolog (ERG) rearrangements are two of the most common genetic abnormalities associated with prostate cancer. Prior studies have demonstrated these alterations portend worse clinical outcomes. Our objective is to evaluate the impact of biopsy-determined PTEN losses and TMPRSS2-ERG fusion on biochemical progression-free survival (bPFS) and overall survival (OS) in patients who receive SBRT for localized prostate cancer.Methods/materialsPatients received SBRT for localized prostate cancer on a prospective quality-of-life (QoL) and cancer outcomes study. For each patient, the single biopsy core with the highest grade/volume of cancer was evaluated for PTEN and ERG abnormalities. Differences in baseline patient and disease characteristics between groups were analyzed using ANOVA for age and χ2 for categorical groupings. bPFS and OS were calculated using the Kaplan Meier (KM) method with Log-Rank test comparison between groups. Predictors of bPFS and OS were identified using the Cox proportional hazards method. For all analyses, p <0.05 was considered statistically significant.ResultsNinety-nine consecutive patients were included in the analysis with a median follow-up of 72 months. A statistically significant improvement in bPFS (p = 0.018) was observed for wild type ERG patients with an estimated 5-year bPFS of 94.1% vs. 72.4%. Regarding PTEN mutational status, significant improvements in were observed in both bPFS (p = 0.006) and OS (p < 0.001), with estimated 5-year bPFS rates of 91.0% vs. 67.9% and 5-year OS rates of 96.4% vs. 79.4%. When including both ERG and PTEN mutational status in the analysis, there were statistically significant differences in both bPFS (p = 0.011) and OS (p < 0.001). The estimated 5-year bPFS rates were 100%, 76.6%, 72.9%, and 63.8% for patients with ERG+/PTEN+, ERG-/PTEN+, ERG+/PTEN-, and ERG-/PTEN- phenotypes respectively. The estimated 5-year OS rates were 93.9%, 100%, 80.0%, and 78.7% for patients with ERG+/PTEN+, ERG-/PTEN+, ERG+/PTEN-, and ERG-/PTEN- phenotypes respectively.ConclusionERG rearrangements and PTEN deletions detected on biopsy samples are associated with poorer oncologic outcomes in prostate cancer patients treated with SBRT and merit further study in a dedicated prospective trial

Rhinitis associated with asthma is distinct from rhinitis alone: TARIA‐MeDALL hypothesis

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one-airway-one-disease,” coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined that the “one-airway-one-disease” concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme “allergic” (asthma) phenotype combining asthma, rhinitis, and conjunctivitis.info:eu-repo/semantics/publishedVersio

Concepts for the Development of Person-Centered, Digitally Enabled, Artificial Intelligence–Assisted ARIA Care Pathways (ARIA 2024)

Funding Information: This work has received funding from ARIA (Allergic Rhinitis and its Impact of Asthma); CATALYSE (Climate Action To Advance HeaLthY Societies in Europe), the European Union\u2019s Horizon Europe research and innovation program under grant agreement no. 101057131; FRAUNHOFER Institute for Translational Medicine and Pharmacology (ITMP), Immunology and Allergology, Berlin, Germany; University of Porto, Portugal; and MASK-air, which has been supported by EU grants (Impact of air Pollution on Asthma and Rhinitis [POLLAR] project of the European Institute of Innovation and Technology Health; Structural and Development Funds, R\u00E9gion Languedoc Roussillon and Provence-Alpes-C\u00F4te d\u2019Azur; Twinning, European Innovation Partnership on Active and Healthy Ageing, DG Sant\u00E9 and DG Connect); educational grants from Mylan-Viatris, Allergologisk Laboratorium K\u00F8benhavn, GlaxoSmithKline, Novartis, Stallerg\u00E8nes-Greer, and Noucor; and funding from Breathing Together Onlus Association (Associazione Respiriamo Insieme Onlus), Italy; Esp\u00EDritu Santo University, Samborond\u00F3n, Ecuador; Finnish Anti-Tuberculosis Association Foundation and Tampere Tuberculosis Foundation; GA 2 LEN; German Allergy Society AeDA (\u00C4rzteverband Deutscher Allergologen); IPOKRaTES (International Postgraduate Organization for Knowledge transfer, Research and Teaching Excellent Students) Lithuania Fund; Polish Society of Allergology (POLSKIE TOWARZYSTWO ALLERGOLOGICZNE); and University of Li\u00E8ge, Belgium. Funding Information: Conflicts of interest: J. Bousquet reports personal fees from Cipla, Menarini, Mylan, Novartis, Purina, Sanofi-Aventis, Teva, Noucor, other from KYomed-Innov, and other from Mask-air-SAS, outside the submitted work. M. Blaiss reports personal fees from Sanofi, personal fees from Regeneron, personal fees from ALK, personal fees from Merck, personal fees from AstraZeneca, personal fees from GSK, personal fees from Prollergy, personal fees from Lanier Biotherapeutics, and nonfinancial support from Bryn Phama, outside the submitted work. J. Lity\u0144ska reports personal fees from Evidence Prime Sp. z o.o., outside the submitted work. T. Iinuma reports grants from Sanofi, outside the submitted work. P. Tantilipikorn reports grants from Abbott, other from GSK, and other from Sanofi Aventis, outside the submitted work. T. Haahtela reports personal fees from Orion Pharma, outside the submitted work. Publisher Copyright: © 2024 The AuthorsThe traditional healthcare model is focused on diseases (medicine and natural science) and does not acknowledge patients’ resources and abilities to be experts in their own lives based on their lived experiences. Improving healthcare safety, quality, and coordination, as well as quality of life, is an important aim in the care of patients with chronic conditions. Person-centered care needs to ensure that people's values and preferences guide clinical decisions. This paper reviews current knowledge to develop (1) digital care pathways for rhinitis and asthma multimorbidity and (2) digitally enabled, person-centered care.1 It combines all relevant research evidence, including the so-called real-world evidence, with the ultimate goal to develop digitally enabled, patient-centered care. The paper includes (1) Allergic Rhinitis and its Impact on Asthma (ARIA), a 2-decade journey, (2) Grading of Recommendations, Assessment, Development and Evaluation (GRADE), the evidence-based model of guidelines in airway diseases, (3) mHealth impact on airway diseases, (4) From guidelines to digital care pathways, (5) Embedding Planetary Health, (6) Novel classification of rhinitis and asthma, (7) Embedding real-life data with population-based studies, (8) The ARIA-EAACI (European Academy of Allergy and Clinical Immunology) strategy for the management of airway diseases using digital biomarkers, (9) Artificial intelligence, (10) The development of digitally enabled, ARIA person-centered care, and (11) The political agenda. The ultimate goal is to propose ARIA 2024 guidelines centered around the patient to make them more applicable and sustainable.proofinpres

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity