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Purpose: Proton beam therapy (PBT) has recently been included in Japan's health insurance benefit package for certain cancer types. This study aimed to determine the cost-effectiveness of PBT as a replacement for conventional three-dimensional conformal radiotherapy (3D-CRT) for locally advanced esophageal cancer (LAEC) that is not covered by social insurance. Methods: We estimated the incremental cost-effectiveness ratio (ICER) of PBT as a replacement for 3D-CRT, using clinical evidence from the literature and expert opinions. We used an economic model, decision tree, and Markov model to illustrate the courses followed by patients with LAEC. Effectiveness was estimated as quality-adjusted life years (QALY) using utility weights for the health state. Social insurance fees were calculated as costs. We assumed two base cases depending on the two existing levels of fees for PBT in social insurance: 2,735,000 Japanese yen (US$20,652) or 1,600,000 yen (US$13,913). The stability of the ICER against these assumptions was appraised using sensitivity analysis. Results: The effectiveness of PBT and 3D-CRT was 2.62 and 2.51 QALY, respectively. The estimated ICER was 14,025,268 yen (US$121,958) per QALY for the higher fee level and 7,026,402 yen (US$61,099) for the lower fee level. According to the Japanese threshold for cost-effectiveness of anticancer therapy of 7,500,000 yen (US$65,217) per QALY gain, the inclusion of PBT for LAEC in the benefit package of social insurance is cost-effective if a lower fee is applied. Conclusion: PBT is a cost-effective alternative to 3D-CRT for LAEC and making it available to patients under social insurance could be justifiable. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most common neurodegenerative disease. The development of PD is closely linked to genetic and environmental factors, with GBA1 variants being the most common genetic risk. Mutations in the GBA1 gene lead to reduced activity of the coded enzyme, glucocerebrosidase, which mediates the development of PD by affecting lipid metabolism (especially sphingolipids), lysosomal autophagy, endoplasmic reticulum, as well as mitochondrial and other cellular functions. Clinically, PD with GBA1 mutations (GBA1-PD) is characterized by particular features regarding the progression of symptom severity. On the therapeutic side, the discovery of the relationship between GBA1 variants and PD offers an opportunity for targeted therapeutic interventions. In this review, we explore the genotypic and phenotypic correlations, etiologic mechanisms, biomarkers, and therapeutic approaches of GBA1-PD and summarize the current state of research and its challenges. [ABSTRACT FROM AUTHOR]

Upper tract urothelial carcinoma (UTUC) is a rare but aggressive neoplasm. Currently, there are few reliable and widely used prognostic biomarkers of this disease. The purpose of this study was to assess the prognostic value of blood-, tissue- and urine-based biomarkers in patients with UTUC. A comprehensive literature search was conducted using the PubMed, Cochrane and Embase databases. Case reports, editorials and non-peer-reviewed literature were excluded from the analysis. As a result, 94 articles were included in this review. We evaluated the impact of 22 blood-based, 13 tissue-based and 4 urine-based biomarkers and their influence on survival outcomes. The neutrophil–lymphocyte ratio, albumin, C-reactive protein, De Ritis ratio, renal function and fibrinogen, which are currently mentioned in the European Association of Urology (EAU) guidelines, are well researched and most probably allow for a reliable prognosis estimate. However, our review highlights a number of other promising biomarkers that could potentially predict oncological outcomes in patients with UTUC. Nonetheless, the clinical value of some prognostic factors remains uncertain due to the lack of comprehensive studies. [ABSTRACT FROM AUTHOR]

Objective : We investigated how treating large brain metastasis (LBM) using 2-day fraction Gamma Knife radiosurgery (GKRS) affects tumor control and patient survival. A prescription dose of 10.3 Gy was applied for 2 consecutive days, with a biologically effective dose equivalent to a tumor single-fraction dose of 16.05 Gy and a brain single-fraction dose of 15.12 Gy. Methods : Between November 2017 and December 2021, 42 patients (mean age, 68.3 years; range, 50–84 years; male, 29 [69.1%]; female, 13 [30.9%]) with 44 tumors underwent 2-day fraction GKRS to treat large volume brain metastasis. The main cancer types were non-small cell lung cancer (n=16), small cell lung cancer (n=7), colorectal cancer (n=7), breast cancer (n=3), gastric cancer (n=2), and other cancers (n=7). Twenty-one patients (50.0%) had a single LBM, 19 (46.3%) had a single LBM and other metastases, and two had two (4.7%) large brain metastases. At the time of the 2-day fraction GKRS, the tumors had a mean volume of 23.1 mL (range, 12.5–67.4). On each day, radiation was administered at a dose of 10.3 Gy, mainly using a 50% isodose-line. Results : We obtained clinical and magnetic resonance imaging follow-up data for 34 patients (81%) with 35 tumors, who had undergone 2-day fraction GKRS. These patients did not experience acute or late radiation-induced complications during follow-up. The median and mean progression-free survival (PFS) periods were 188 and 194 days, respectively. The local control rates at 6, 9, and 12 months were 77%, 40%, and 34%, respectively. The prognostic factors related to PFS were prior radiotherapy (p=0.019) and lung cancer origin (p=0.041). Other factors such as tumor volumes, each isodose volumes, and peri-GKRS systemic treatment were not significantly related to PFS. The overall survival period of the 44 patients following repeat stereotactic radiosurgery (SRS) ranged from 15–878 days (median, 263±38 days; mean, 174±43 days) after the 2-day fraction GKRS. Eight patients (18.2%) were still alive. Conclusion : Considering the unsatisfactory tumor control, a higher prescription dose should be needed in this procedure as a salvage management. Moreover, in the treatment for LBM with fractionated SRS, using different isodoses and prescription doses at the treatment planning for LBMs should be important. However, this report might be a basic reference with the same fraction number and prescription dose in the treatment for LBMs with frame-based SRS. [ABSTRACT FROM AUTHOR]

Simple Summary: This study identified the risk factors of non-local recurrence of isocitrate dehydrogenase (IDH) wild-type glioblastoma, a highly aggressive brain tumor. We found that subventricular zone involvement significantly increased the risk of non-local recurrence, with the tumor contacting the trigone of the lateral ventricle and tending to develop subependymal dissemination. A meta-analysis of previous studies confirmed subventricular zone involvement and O-6-methylguanine DNA methyltransferase promoter methylation as risk factors for non-local recurrence. In contrast, ventricular opening via surgery did not increase the risk of non-local recurrence. These findings emphasize the need for tailored therapeutic strategies based on tumor location and molecular characteristics and provide valuable guidance for clinical decision-making in managing recurrent glioblastoma. Isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) is a highly aggressive brain tumor with a high recurrence rate despite adjuvant treatment. This study aimed to evaluate the risk factors for non-local recurrence of GBM. In the present study, we analyzed 104 GBMs with a single lesion (non-multifocal or multicentric). Univariate analysis revealed that subventricular zone (SVZ) involvement was significantly associated with non-local recurrence (hazard ratio [HR]: 2.09 [1.08–4.05]). Tumors in contact with the trigone of the lateral ventricle tended to develop subependymal dissemination (p = 0.008). Ventricular opening via surgery did not increase the risk of non-local recurrence in patients with SVZ involvement (p = 0.190). A systematic review was performed to investigate the risk of non-local recurrence, and 21 studies were identified. A meta-analysis of previous studies confirmed SVZ involvement (odds ratio [OR]: 1.30 [1.01–1.67]) and O-6-methylguanine DNA methyltransferase promoter methylation (OR: 1.55 [1.09–2.20]) as significant risk factors for local recurrence. A time-dependent meta-analysis revealed a significant association between SVZ involvement and dissemination (HR: 1.69 [1.09–2.63]), while no significant association was found for distant recurrence (HR: 1.29 [0.74–2.27]). Understanding SVZ involvement and specific tumor locations associated with non-local recurrence provides critical insights for the management of GBM. [ABSTRACT FROM AUTHOR]

Background: Modern radiotherapy exemplified by intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), has transformed esophageal cancer treatment. Facing challenges in treating thoracic esophageal cancer near vital organs, this study introduces a regression model-based decision support tool for the optimal selection of radiotherapy techniques. Methods: We enrolled 106 patients diagnosed with locally advanced thoracic esophageal cancer in this study and designed individualized IMRT and VMAT radiotherapy plans for each patient. Detailed dosimetric analysis was performed to evaluate the differences in dose distribution between the two radiotherapy techniques across various thoracic regions. Single-factor and multifactorial logistic regression analyses were employed to establish predictive models (P1 and P2) and factors such as TLV/PTV ratio. These models were used to predict the compliance and potential advantages of IMRT and VMAT plans. External validation was performed in a validation group of 30 patients. Results: Using predictive models, we developed a data-driven decision support tool. For upper thoracic cases, VMAT plans were recommended; for middle/ lower thoracic cases, the tool guided VMAT/IMRT choices based on TLV/PTV ratio. Models P1 and P2 assessed IMRT and VMAT compliance. In validation, the tool showed high specificity (90.91%) and sensitivity (78.95%), differentiating IMRT and VMAT plans. Balanced performance in compliance assessment demonstrated tool reliability. Conclusion: In summary, our regression model-based decision support tool provides practical guidance for selecting optimal radiotherapy techniques for thoracic esophageal cancer patients. Despite a limited sample size, the tool demonstrates potential clinical benefits, alleviating manual planning burdens and ensuring precise, individualized treatment decisions for patients. [ABSTRACT FROM AUTHOR]

Background: Limited literature exists on the feasibility and effectiveness of integrating stereotactic ablative radiotherapy (SABR) techniques with hyperfractionated regimens for patients with lung cancer. This study aims to assess whether the SABR technique with hyperfractionation can potentially reduce lung toxicity. Methods: We utilized the linear‐quadratic model to find the optimal fraction to maximize the tumor biological equivalent dose (BED) to normal‐tissue BED ratio. Validation was performed by comparing the SABR plans with 50 Gy/5 fractions and hyperfractionationed plans with 88.8 Gy/74 fractions with the same tumor BED and planning criteria for 10 patients with early‐stage lung cancer. Mean lung BED, Lyman–Kutcher–Burman (LKB) normal tissue complication probability (NTCP), critical volume (CV) criteria (volume below BED of 22.92 and 25.65 Gy, and mean BED for lowest 1000 and 1500 cc) and the percentage of the lung receiving 20Gy or more (V20) were compared using the Wilcoxon signed‐rank test. Results: The transition point occurs when the tumor‐to‐normal tissue ratio (TNR) of the physical dose equals the TNR of α/β in the BED dose‐volume histogram of the lung. Compared with the hypofractionated regimen, the hyperfractionated regimen is superior in the dose range above but inferior below the transition point. The hyperfractionated regimen showed a lower mean lung BED (6.40 Gy vs. 7.73 Gy) and NTCP (3.50% vs. 4.21%), with inferior results concerning CV criteria and higher V20 (7.37% vs. 7.03%) in comparison with the hypofractionated regimen (p < 0.01 for all). Conclusions: The hyperfractionated regimen has an advantage in the high‐dose region of the lung but a disadvantage in the low‐dose region. Further research is needed to determine the superiority between hypo‐ and hyperfractionation. [ABSTRACT FROM AUTHOR]

Simple Summary: We retrospectively evaluated the clinical outcomes and prognostic factors of 127 patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with first-line androgen receptor signaling inhibitors (ARSI) in real-world clinical practice. Overall survival (OS), metastatic-free survival (MFS), and prostate-specific antigen–progression-free survival (PSA–PFS) from the initiation of ARSI were assessed. The median OS and MFS for all patients were 79.0 and 42.0 months, respectively. Median PSA–PFS varied among patients treated with enzalutamide, abiraterone acetate, apalutamide, and darolutamide (27.0, 20.0, 10.0, and 14.0 months, respectively; p = 0.33). Multivariate analysis indicated that a baseline PSA level of ≥3.67 ng/mL (p = 0.002) was significantly associated with poorer OS prognosis. ARSI demonstrated favorable efficacy in nmCRPC patients, with no significant differences in clinical outcomes among different types of ARSI. High baseline PSA of ARSI was found to have a significantly poor prognosis associated with OS. We conducted a retrospective evaluation of the clinical outcomes and prognostic factors in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with first-line androgen receptor signaling inhibitors (ARSI) in real-world clinical practice in Japan. Between 2012 and 2023, a total of 127 consecutive patients with nmCRPC received ARSI treatment. Overall survival (OS), metastatic-free survival (MFS), and prostate-specific antigen–progression-free survival (PSA–PFS) from ARSI initiation were assessed using the Kaplan–Meier methodology. Clinical factors associated with OS in nmCRPC were analyzed using the Cox proportional hazards model. Among the patients, 72, 26, 12, and 17 received enzalutamide (ENZ), abiraterone (ABI), apalutamide (APA), and darolutamide (DARO) as first-line therapy. The median OS and MFS for all patients were 79.0 and 42.0 months, respectively. Median PSA–PFS was 27.0, 20.0, 10.0, and 14.0 months for patients treated with ENZ, ABI, APA, and DARO, respectively (p = 0.33). Multivariate analysis revealed that a baseline PSA level ≥ 3.67 ng/mL at ARSI initiation was significantly associated with poorer OS (p = 0.002). ARSI demonstrated favorable efficacy in nmCRPC patients. There were no significant differences in clinical outcomes among different types of ARSI therapy for nmCRP. Elevated baseline PSA at ARSI initiation was significantly associated with poorer OS. [ABSTRACT FROM AUTHOR]

Background: Fractionated stereotactic radiosurgery (fSRS) is an important treatment strategy for unresected brain metastases. We previously reported that a good volumetric response 6 months after fSRS can be the first step for local control. Few studies have reported the association between gross tumor volume (GTV) dose, volumetric response, and local control in patients treated with the same number of fractions. Therefore, in this study, we aimed to investigate the GTV dose and volumetric response 6 months after fSRS in five daily fractions and identify the predictive GTV dose for local failure (LF) for unresected brain metastasis. Methods: This retrospective study included 115 patients with 241 unresected brain metastases treated using fSRS in five daily fractions at our hospital between January 2013 and April 2022. The median prescription dose was 35 Gy (range, 30–35 Gy) in five fractions. The median follow-up time after fSRS was 16 months (range, 7–66 months). Results: GTV D80 > 42 Gy and GTV D98 > 39 Gy were prognostic factors for over 65% volume reduction (odds ratio, 3.68, p < 0.01; odds ratio, 4.68, p < 0.01, respectively). GTV D80 > 42 Gy was also a prognostic factor for LF (hazard ratio, 0.37; p = 0.01). Conclusions: GTV D80 > 42 Gy in five fractions led to better volume reduction and local control. The goal of planning an inhomogeneous dose distribution for fSRS in brain metastases may be to increase the GTV D80 and GTV D98. Further studies on inhomogeneous dose distributions are required. [ABSTRACT FROM AUTHOR]

Background: Endoscopic submucosal dissection (ESD) is a potentially efficient therapeutic intervention for superficial esophageal cancer. Additional treatment such as chemoradiotherapy (CRT) or esophagectomy is recommended in cases of muscularis mucosa invasion with positive resection margins or lymphovascular invasion or submucosal layer invasion, which are considered noncurative ESD, due to an increased risk of lymph node metastasis. However, the adequacy of additional CRT after near-circumferential or full-circumferential noncurative ESD has not been fully discussed. In this study, we retrospectively evaluated the efficacy and toxicity of additional CRT for superficial esophageal squamous cell carcinoma (SCC) after near-circumferential or full-circumferential noncurative ESD, which was defined as a mucosal defect measuring ≥ 3/4 of the esophageal circumference. Methods: We retrospectively evaluated 24 patients who received additional CRT for superficial esophageal SCC after near-circumferential or full-circumferential noncurative ESD between 2012 and 2018. Elective nodal irradiation (ENI) was performed in all patients and boost irradiation (BI) was performed after ENI in 4 patients with positive resection margins. The prescription doses of ENI and BI were 41.4 Gy in 23 fractions and 9 Gy in 5 fractions, respectively. Concurrent chemotherapy (a combination of cisplatin or nedaplatin and 5-fluorouracil) was administered to all patients. Results: The 3-year and 5-year overall survival rates were 92% and 78%, respectively, while the 3-year and 5-year progression-free survival rates were 83% and 70%, respectively. Grade 2 esophageal stenosis occurred in 8 (33%) patients. There was no case of Grade 3 or worse esophageal stenosis. Among them, 4 (17%) patients developed stenosis before additional CRT, which persisted after the completion of additional CRT. The remaining 4 (17%) patients developed de novo stenosis within 5 months following the completion of additional CRT. One patient (4%) still requires regular bougie dilation. Grade 3 and Grade 4 acute toxicity, including anemia, neutropenia, thrombocytopenia, and esophagitis occurred in 1 (4%) and 0 (0%), 6 (25%) and 1 (4%), 1 (4%) and 0 (0%), and 1 (4%) and 0 (0%) patients, respectively. One (4%) patient who underwent salvage CRT for the out-of-field lymph node recurrence died with acute myeloid leukemia. Conclusions: Additional CRT is a viable treatment option even in patients who have undergone near-circumferential or full-circumferential noncurative ESD. Esophageal stenosis after additional CRT following near-circumferential or full-circumferential noncurative ESD is manageable and acceptable. [ABSTRACT FROM AUTHOR]

Anderson–Fabry disease (AFD) is a genetic sphingolipidosis involving virtually the entire body. Among its manifestation, the involvement of the central and peripheral nervous system is frequent. In recent decades, it has become evident that, besides cerebrovascular damage, a pure neuronal phenotype of AFD exists in the central nervous system, which is supported by clinical, pathological, and neuroimaging data. This neurodegenerative phenotype is often clinically characterized by an extrapyramidal component similar to the one seen in prodromal Parkinson's disease (PD). We analyzed the biological, clinical pathological, and neuroimaging data supporting this phenotype recently proposed in the literature. Moreover, we compared the neurodegenerative PD phenotype of AFD with a classical monogenic vascular disease responsible for vascular parkinsonism and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). A substantial difference in the clinical and neuroimaging features of neurodegenerative and vascular parkinsonism phenotypes emerged, with AFD being potentially responsible for both forms of the extrapyramidal involvement, and CADASIL mainly associated with the vascular subtype. The available studies share some limitations regarding both patients' information and neurological and genetic investigations. Further studies are needed to clarify the potential association between AFD and extrapyramidal manifestations. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) ranks among the 15 most prevalent cancers globally, characterized by aggressive growth and late-stage diagnosis. Advances in imaging and surgical techniques have redefined the classification of pancreatic PDAC into resectable, borderline resectable, and locally advanced pancreatic cancer. While surgery remains the most effective treatment, only 20% of patients are eligible at diagnosis, necessitating innovative strategies to improve outcomes. Therefore, traditional treatment paradigms, primarily surgical resection for eligible patients, are increasingly supplemented by neoadjuvant therapies (NAT), which include chemotherapy, radiotherapy, or a combination of both. By administering systemic therapy prior to surgery, NAT aims to reduce tumor size and increase the feasibility of complete surgical resection, thus enhancing overall survival rates and potentially allowing more patients to undergo curative surgeries. Recent advances in treatment protocols, such as FOLFIRINOX and gemcitabine-nab-paclitaxel, now integral to NAT strategies, have shown promising results in increasing the proportion of patients eligible for surgery by effectively reducing tumor size and addressing micrometastatic disease. Additionally, they offer improved response rates and survival benefits compared to traditional regimes. Despite these advancements, the role of NAT continues to evolve, necessitating ongoing research to optimize treatment regimens, minimize adverse effects, and identify patient populations that would benefit most from these approaches. Through a detailed analysis of current literature and recent clinical trials, this review highlights the transformative potential of NAT in managing PDAC, especially in patients with borderline resectable or locally advanced stages, promising a shift towards more personalized and effective management strategies for PDAC. [ABSTRACT FROM AUTHOR]

Objectives: The clinical decision-making regarding choosing surgery alone (SA) or surgery followed by postoperative adjuvant chemotherapy (SPOCT) in esophageal squamous cell carcinoma (ESCC) remains controversial. We aim to propose a pre-therapy PET/CT image-based deep learning approach to improve the survival benefit and clinical management of ESCC patients. Methods: This retrospective multicenter study included 837 ESCC patients from three institutions. Prognostic biomarkers integrating six networks were developed to build an ESCC prognosis (ESCCPro) model and predict the survival probability of ESCC patients treated with SA and SPOCT. Patients who did not undergo surgical resection were in a control group. Overall survival (OS) was the primary end-point event. The expected improvement in survival prognosis with the application of ESCCPro to assign treatment protocols was estimated by comparing the survival of patients in each subgroup. Seven clinicians with varying experience evaluated how ESCCPro performed in assisting clinical decision-making. Results: In this retrospective multicenter study, patients receiving SA had a median OS 9.2 months longer than controls. No significant differences in survival were found between SA patients with predicted poor outcomes and the controls (p > 0.05). It was estimated that if ESCCPro was used to determine SA and SPOCT eligibility, the median OS in the ESCCPro-recommended SA group and SPOCT group would have been 15.3 months and 24.9 months longer, respectively. In addition, ESCCPro also significantly improved prognosis accuracy, certainty, and the efficiency of clinical experts. Conclusion: ESCCPro assistance improved the survival benefit of ESCC patients and the clinical decision-making among the two treatment approaches. Critical relevance statement: The ESCCPro model for treatment decision-making is promising to improve overall survival in ESCC patients undergoing surgical resection and patients undergoing surgery followed by postoperative adjuvant chemotherapy. Key Points: ESCC is associated with a poor prognosis and unclear ideal treatments. ESCCPro predicts the survival of patients with ESCC and the expected benefit from SA. ESCCPro improves clinicians' stratification of patients' prognoses. [ABSTRACT FROM AUTHOR]

This review addresses the role of tight junction proteins at the blood-brain barrier (BBB). Their expression is described, and their role in physiological and pathological processes at the BBB is discussed. Based on this, new approaches are depicted for paracellular drug delivery and diagnostics in the treatment of cerebral diseases. Recent data provide convincing evidence that, in addition to its impairment in the course of diseases, the BBB could be involved in the aetiology of CNS disorders. Further progress will be expected based on new insights in tight junction protein structure and in their involvement in signalling pathways. [ABSTRACT FROM AUTHOR]

Modern medicine has allowed for many advances in neurological and neurodegenerative disease (ND). However, the number of patients suffering from brain diseases is ever increasing and the treatment of brain diseases remains an issue, as drug efficacy is dramatically reduced due to the existence of the unique vascular structure, namely the blood–brain barrier (BBB). Several approaches to enhance drug delivery to the brain have been investigated but many have proven to be unsuccessful due to limited transport or damage induced in the BBB. Alternative approaches to enhance molecular delivery to the brain have been revealed in recent studies through the existence of molecular delivery pathways that regulate the passage of peripheral molecules. In this review, we present recent advancements of the basic research for these delivery pathways as well as examples of promising ventures to overcome the molecular hurdles that will enhance therapeutic interventions in the brain and potentially save the lives of millions of patients. [ABSTRACT FROM AUTHOR]

Background: This paper aimed to investigate the radiation dosimetry and dose deposition to the surrounded organs at risk (OARs) with different radial and longitudinal margins based on the normal tissue complication probability (NTCP) and dose-volume histogram (DVH) methods. Materials and Methods: Fifteen patients with histologically diagnosed esophageal cancer were retrospectively selected. From the clinical target volume (CTV), eight planning target volumes (PTV) were expanded for each patient, with one group of four radial margins (3mm, 5mm, 7mm, 10mm) and the other group of four longitudinal margins (3mm, 5mm, 7mm, 10mm). Then, eight plans with the prescription dose of 50.4Gy were designed in the tomotherapy system. Within each group, doses for the OARs and NTCP-based risk of pneumonitis and pericardial disease were compared. Results: Almost all the dose parameters in both groups, except for the Dmax (maximum dose) of the spinal cord in the longitudinal direction, showed significant linearly increasing trends with the expansion of margins. For same dose parameters, the increased slopes in the radial direction were larger than those in the longitudinal. Heart V30Gy (the percent volume of receiving 30Gy) grew fastest compared to other clinical constraint indexes in both groups, and the most significant difference in the risk of pneumonitis was observed in the radial group when the margin was expanded from 3 to 10mm. Conclusions: In order to lower the likelihood of radiation-related toxicity, radial margin expansion should be more strictly controlled in the radiotherapy of esophageal cancer with tomotherapy. [ABSTRACT FROM AUTHOR]

Background/Aim: Definitive chemoradiotherapy with cisplatin (CDDP) plus 5-fluorouracil is the standard treatment for locally advanced esophageal squamous cell carcinoma (LA-ESCC); however, CDDP is unsuitable for patients with cardiac and/or renal dysfunction. Based on the results of the PRODIGE5/ACCORD17 trial, 5-fluorouracil and leucovorin with oxaliplatin plus radiotherapy (FOLFOX-RT) has been recognized as a treatment option. However, the efficacy and safety of FOLFOX-RT is still unclear in Japan. Patients and Methods: Medical records were reviewed for patients with LA-ESCC who received FOLFOX-RT between April 2019 and July 2021 at our institution. We evaluated complete response rate, progression-free survival (PFS), overall survival (OS), and adverse events. Results: Fifteen patients were analyzed and median age was 72.5 years (range=51-83 years). All patients completed three courses of FOLFOX and the planned radiotherapy. The complete response rate was 40.0%. With a median follow-up of 10.6 months, the 6-month PFS rate was 63.0% (95%CI=32.3-82.8%), and the 6-month OS rate was 85.7% (95%CI=53.9-96.2%). Common adverse events were esophagitis (80.0%), leukopenia (53.3%), fatigue (53.3%), and neutropenia (46.7%). Only one patient had grade 4 esophageal perforation. Conclusion: FOLFOX-RT for LA-ESCC was well tolerated and could be a treatment option for CDDP-intolerant patients. [ABSTRACT FROM AUTHOR]

Background: Pineal parenchymal cell tumors constitute a rare group of primary central nervous system neoplasms (less than 1%). Their classification, especially the intermediate subtype (PPTIDs), remains challenging. Methods: A literature review was conducted, navigating through anatomo-pathological, radiotherapy, and neurosurgical dimensions, aiming for a holistic understanding of these tumors. Results: PPTIDs, occupying an intermediate spectrum of malignancy, reveal diverse histological patterns, mitotic activity, and distinct methylation profiles. Surgical treatment is the gold standard, but when limited to partial removal, radiotherapy becomes crucial. While surgical approaches are standardized, due to the low prevalence of the pathology and absence of randomized prospective studies, there are no shared guidelines about radiation treatment modalities. Conclusion: Surgical removal remains pivotal, demanding a personalized approach based on the tumor extension. This review underscores the considerable variability in treatment approaches and reported survival rates within the existing literature, emphasizing the need for ongoing research to better define optimal therapeutic strategies and prognostic factors for PPTIDs, aiming for further and more detailed stratification among them. [ABSTRACT FROM AUTHOR]

Simple Summary: Most pancreatic cancer patients present with locally advanced tumors non-amenable to surgical resection or other radical treatments. The most used form of radiotherapy in those cases is palliative-intended non-ablative radiotherapy, mainly to alleviate the significant symptoms caused by the local progression of pancreatic primaries. Research in this area is severely under-represented in the literature and the guidelines for palliative radiotherapy dose prescriptions in this setting are based on very scarce data. The paucity of studies in this area contrasts with that for palliative radiotherapy for bone, brain, liver, and lung diseases, where various radiotherapy strategies have been evaluated, and evidence-based recommendations guide practice. An early step toward optimizing palliative radiotherapy use for pancreatic cancer is quantifying and describing its current use. Here, we describe the use of non-ablative palliative radiotherapy among patients treated for primary pancreatic tumors in our institution over 15 years. We studied the use of palliative radiotherapy (RT) among patients with primary, non-curable, locally advanced pancreatic cancer. In this subset of patients, with very poor survival, various palliative RT dose fractionation schemes are used; but, in the absence of a guideline, practice patterns vary, and dose choice is mainly based on the physician's intuition. We divided the patients into three groups, according to the dose fractionation schedules received: low (A), intermediate (B), and high (C) dose groups, to study the potential differences in outcome between the different dose prescriptions. Cohort: n = 184. Median age: 69 years. Male: n = 105 (57%), female: n = 79 (43%). Stage IV: n = 117 (64%). T4: n = 127 (69%). Tumor location: head: n = 109 (59%), body: n = 37 (20%), tail: n = 25 (14%), neck: n = 11 (6%), and uncinate: n = 2 (1%). Prior systemic therapy: n = 66 (36%). Most common dose fractionations received: 20 Gy in five fractions n = 67 (36%), 30 Gy in 10 fractions n = 49 (27%), and 8 Gy in one fraction n = 23 (13%). Group A: n = 33 (18%), median overall survival (OS) 19 days (95% CI 4–33). Group B: n = 84 (46%), median OS 52 days (95% CI 43–60). Group C: n = 67 (36%), median OS 126 days (95% CI 77–174). Median days to in-field progression: Group A 59 days (range 7–109), Group B 96 days (range 19–173), and Group C 97 days (range 13–475). To our knowledge, this is the largest reported retrospective cohort of patients receiving non-ablative palliative RT to treat their primary pancreatic tumors. Most patients had metastatic disease, T4 tumors of the pancreatic head and had not received prior systemic therapy. A significant survival benefit was seen favoring the high dose/longer RT fractionation group, presumably due to appropriate patient selection rather than an RT effect. Despite the relatively short median overall survival, one fifth of the patients were found to experience an in-field progression following RT. [ABSTRACT FROM AUTHOR]

Simple Summary: A review was conducted to examine treatment strategies for oligo-recurrence with a controlled primary lesion and sync-oligometastases with an active primary lesion in esophageal squamous cell carcinoma. Although oligo-recurrence cases with possible therapeutic interventions had better outcomes, there may be selection bias due to retrospective studies. However, it is very clear that a small number of cases of oligometastases can be cured by local therapy, including surgical resection of metastases and radical chemoradiotherapy. The results of several ongoing clinical trials may lead to new treatment strategies for patients with oligometastases from esophageal squamous cell carcinoma in the future. Patients with oligometastases show distant relapse in only a limited number of regions. Local therapy such as surgical resection, radiotherapy, chemoradiotherapy, and radiofrequency ablation for the relapsed sites may thus improve patient survival. Oligometastases are divided into oligo-recurrence and sync-oligometastases. Oligo-recurrence indicates a primary lesion that is controlled, and sync-oligometastases indicate a primary lesion that is not controlled. The management of oligo-recurrence and sync-oligometastases in esophageal squamous cell carcinoma has not been clearly established, and treatment outcomes remain equivocal. We reviewed 14 articles, including three phase II trials, that were limited to squamous cell carcinoma. Multimodal treatment combining surgical resection and chemoradiotherapy for oligo-recurrence of esophageal squamous cell carcinoma appears to be a promising treatment. With the development of more effective chemotherapy and regimens that combine immune checkpoint inhibitors, it will become more likely that sync-oligometastases that were unresectable at the initial diagnosis can be brought to conversion surgery. Currently, a randomized, controlled phase III trial is being conducted in Japan to compare a strategy for performing definitive chemoradiotherapy and, if necessary, salvage surgery with a strategy for conversion surgery in patients who can be resected by induction chemotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: The standard treatment of choice for inoperable esophageal cancer is concurrent chemoradiation therapy. However, the treatment effect varies among patients. Currently, the optimal dose for esophageal cancer for different histologies is still under debate, and the guidelines still recommend using the same dose to treat both squamous cell carcinoma and adenocarcinoma despite their differences in radiation sensitivity. In this review article, we analyzed previous studies treating esophageal cancers with definitive radiotherapy, with or without concurrent chemotherapy. We found that squamous cell carcinoma shows an overall survival benefit with the use of radiation dose escalation, while no advantage was found for adenocarcinoma. Based on these findings, we suggest that further dose escalation can be performed for esophageal squamous cell carcinoma. Esophageal cancer, ranked as the eighth most prevalent cancer globally, is characterized by a low survival rate and poor prognosis. Concurrent chemoradiation therapy (CCRT) is the standard therapy in the non-surgical treatment of localized carcinoma of the esophagus. Nevertheless, the radiation doses employed in CCRT remain notably lower compared to the curative definite chemoradiation therapy utilized in the management of other carcinomas. In order to increase the local control rates and enhance the treatment outcomes, several clinical trials have used high-dose radiation to analyze the effect of dose escalation. Despite the integration of technically advanced RT schemes such as intensity-modulated radiation therapy (IMRT), the results of these trials have failed to demonstrate a significant improvement in overall survival or local progression-free survival. In this review, we investigated previous clinical trials to determine the ineffectiveness of radiation dose escalation in the context of CCRT for esophageal cancer. We aim to clarify the factors contributing to the limited efficacy of escalated radiation doses in improving patient outcomes. Furthermore, we delve into recent research endeavors, exploring prospective radiation dose modifications being altered based on the histological characteristics of the carcinoma. The exploration of these recent studies not only sheds light on potential refinements to the existing treatment protocols but also seeks to identify novel approaches that may pave the way for more efficacious and personalized therapeutic strategies for esophageal cancer management. [ABSTRACT FROM AUTHOR]

Background: Radiation therapy (RT) is an integral and commonly used therapeutic modality for primary lung cancer. However, radiation-induced lung injury (RILI) limits the irradiation dose used in the lung and is a significant source of morbidity. Disruptions in iron metabolism have been linked to radiation injury, but the underlying mechanisms remain unclear. Purpose: To utilize a targeted radiation delivery approach to induce RILI for the development of a model system to study the role of radiation-induced iron accumulation in RILI. Methods: This study utilizes a Small Animal Radiation Research Platform (SARRP) to target the right lung with a 20 Gy dose while minimizing the dose delivered to the left lung and adjacent heart. Long-term pulmonary function was performed using RespiRate-x64image analysis. Normal-appearing lung volumes were calculated using a cone beam CT (CBCT) image thresholding approach in 3D Slicer software. Quantification of iron accumulation was performed spectrophotometrically using a ferrozine-based assay as well as histologically using Prussian blue and via Western blotting for ferritin heavy chain expression. Results: Mild fibrosis was seen histologically in the irradiated lung using hematoxylin and eosin-stained fixed tissue at 9 months, as well as using a scoring system from CBCT images, the Szapiel scoring system, and the highest fibrotic area metric. In contrast, no changes in breathing rate were observed, and median survival was not achieved up to 36 weeks following irradiation, consistent with mild lung fibrosis when only one lung was targeted. Our study provided preliminary evidence on increased iron content and ferritin heavy chain expression in the irradiated lung, thus warranting further investigation. Conclusions: A targeted lung irradiation model may be a useful approach for studying the long-term pathological effects associated with iron accumulation and RILI following ionizing radiation. [ABSTRACT FROM AUTHOR]

Background & Objective: Previous studies have suggested that the modified Glasgow Prognostic Score (mGPS) could be a potential biomarker for lung cancer (LC). However, the association between mGPS and overall survival (OS) or progression-free survival (PFS) in lung cancer patients remains unclear. The purpose of our study was to investigate possible correlation between mGPS and OS or PFS in LC patients. Methods: An extensive search of PubMed, Cochrane Library, EMbase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Trip Database, Worldwide Science, and Google Scholar databases was done for relevant articles, published prior to May 30, 2021, that report correlation between mGPS and OS or PFS in LC patients. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used as the main parameters for evaluation. Results: A total of 28 studies involving 9,748 lung cancer patients were analysed. The pooled analysis revealed that elevated mGPS (≥ 0) was associated with poor OS (HR=1.54; 95% CI, 1.32-1.77) and PFS (HR=1.49; 95% CI, 1.17-1.82). Furthermore, a significant correlation between mGPS (1 or 2) and OS was observed. However, no significant correlation was found between mGPS (1 or 2) and PFS. Subgroup analysis based on ethnicity demonstrated that mGPS ≥ 0 was associated with worse OS compared to mGPS=0 in both Asian (HR=1.46; 95% CI, 1.04-1.89; p<0.05) and Caucasian (HR=1.64; 95% CI, 1.35-1.94; p<0.05) cohorts of LC patients. Conclusions: Our results demonstrate that positive mGPS is associated with poor survival results. Therefore, mGPS may be used as a biomarker for predicting prognosis in LC patients. [ABSTRACT FROM AUTHOR]

Fistula-associated anal cancer in Crohn's disease (CD) can be challenging to diagnose and treat. Patients with longstanding fistulas in the setting of CD who present with a sudden change in their symptoms should undergo biopsy under anesthesia with extensive sampling, followed by staging imaging. Pelvic magnetic resonance imaging (MRI) can be helpful in identifying the extent of the disease locally. Patients often present in the later stages due to the challenges associated with diagnosing these patients. Two subtypes of this disease include squamous cell carcinoma and adenocarcinoma, and treatment depends on diagnosis. Small sample size and lack of uniform data on treatments make it difficult to say which treatment modalities are optimal, but aggressive combined therapy is likely the best approach for survival. This will include chemotherapy and radiation and often radical resection as well. Despite this, survival is poor, although more recent data suggest that outcomes are improving. [ABSTRACT FROM AUTHOR]

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