Beyond childhood: exploring the state of transitional care in pediatric pilocytic astrocytoma.

OBJECTIVE: Pediatric pilocytic astrocytoma (PPA) requires prolonged follow-up after initial resection. The landscape of transitional care for PPA patients is not well characterized. The authors sought to examine the clinical course and transition to adult care for these patients to better characterize opportunities for improvement in long-term care. METHODS: Pediatric patients (younger than 18 years at diagnosis) who underwent biopsy or resection for PPA between May 2000 and November 2022 at the authors' large academic center were retrospectively reviewed. Patient demographics, tumor characteristics, recurrence, adjuvant therapies, and follow-up data were extracted from the electronic medical record via chart review. Charts of patients who were 18 years or older as of January 1, 2024, were reviewed for adult follow-up notes. RESULTS: The authors identified 315 patients who underwent biopsy or resection for PPA between May 2000 and November 2022. The most common tumor location was posterior fossa (59.7%), and gross-total resection (GTR) was achieved in 187 patients (59.4%). In patients with GTR, progression/recurrence occurred less frequently (8.6% vs 41.4%, p < 0.01) compared to patients with non-GTR. Among 177 patients found to be age-eligible for transition to adult care, the authors found that 31 (17.5%) successfully transitioned. The average age at transition from pediatric to adult care was 21.7 years, and the average age at last known adult follow-up was 25.0 years. The authors found that patients who transitioned to adult care were followed longer (12.5 vs 7.0 years, p < 0.01) and were diagnosed at an older age (12.1 vs 9.6 years, p < 0.01) than their untransitioned counterparts. CONCLUSIONS: The authors found that there was a low rate of successful transition from pediatric to adult care for PPA; 17.5% of age-eligible patients are now cared for by adult providers, whereas an additional 18.6% completed appropriate follow-up during childhood and did not require transition to adult care. These findings underscore opportunities for improvement in the pediatric-to-adult transition process for patients with PPA, particularly for those with non-GTR who were not followed for at least 10 years, during which the risk of disease progression is thought to be highest.

Stemness, invasion, and immunosuppression modulation in recurrent glioblastoma using nanotherapy.

The recurrent nature of glioblastoma negatively impacts conventional treatment strategies leading to a growing need for nanomedicine. Nanotherapeutics, an approach designed to deliver drugs to specific sites, is experiencing rapid growth and gaining immense popularity. Having potential in reaching the hard-to-reach disease sites, this field has the potential to show high efficacy in combatting glioblastoma progression. The presence of glioblastoma stem cells (GSCs) is a major factor behind the poor prognosis of glioblastoma multiforme (GBM). Stemness potential, heterogeneity, and self-renewal capacity, are some of the properties that make GSCs invade across the distant regions of the brain. Despite advances in medical technology and MRI-guided maximal surgical resection, not all GSCs residing in the brain can be removed, leading to recurrent disease. The aggressiveness of GBM is often correlated with immune suppression, where the T-cells are unable to infiltrate the cancer initiating GSCs. Standard of care therapies, including surgery and chemotherapy in combination with radiation therapy, have failed to tackle all the challenges of the GSCs, making it increasingly important for researchers to develop strategies to tackle their growth and proliferation and reduce the recurrence of GBM. Here, we will focus on the advancements in the field of nanomedicine that has the potential to show positive impact in managing glioblastoma tumor microenvironment. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Possible new defining presentation of mosaic tetrasomy 9p: multiple and recurrent pilomatrixoma.

Tetrasomy 9p is a rare genetic syndrome resulting from two additional copies of the short arm of chromosome 9. Symptoms often present in the form of congenital abnormalities including cognitive disabilities, growth retardation, abnormal earlobes, congenital heart disease, and dysmorphia of the skull and face. Current literature suggests patients with tetrasomy 9p may exhibit any combination of these symptoms or, in rare instances, none at all. Although karyotyping, chromosomal microarray, and galactose-1-phosphate uridyltransferase activity analyses are the definitive diagnostic methods used, there remains a need for more robust clinical recognition in cases of mild phenotypic expression. Herein, we present a rare case of mosaic tetrasomy 9p in a long-term survival patient with multiple and recurrent pilomatrixomas, rare benign growths more commonly found in individuals under the age of 20. To our knowledge, only two previous reports have noted concurrent tetrasomy 9p with pilomatrixomas. We are the first to identify this phenotype in an adult tetrasomy 9p patient. Dermatopathology evaluation was conducted to verify our diagnoses. Our aim is to present a unique, additional case suggesting multiple pilomatrixomas as a new defining clinical presentation of mosaic tetrasomy 9p and to review the literature underlying the genetic changes associated with this syndrome.

The Population-level Effect of Adjuvant Therapies on Breast Cancer Recurrence: Application of the Trend-in-Trend Design.

PURPOSE: Breast cancer has an average 10-year relative survival reaching 84%. This favorable survival is due, in part, to the introduction of biomarker-guided therapies. We estimated the population-level effect of the introduction of two adjuvant therapies-tamoxifen and trastuzumab-on recurrence using the trend-in-trend pharmacoepidemiologic study design. METHODS: We ascertained data on women diagnosed with nonmetastatic breast cancer who were registered in the Danish Breast Cancer Group clinical database. We used the trend-in-trend design to estimate the population-level effect of the introduction of (1) tamoxifen for postmenopausal women with estrogen receptor (ER)-positive breast cancer in 1982, (2) tamoxifen for premenopausal women diagnosed with ER-positive breast cancer in 1999, and (3) trastuzumab for women <60 years diagnosed with human epidermal growth factor receptor 2-positive breast cancer in 2007. RESULTS: For the population-level effect of the introduction of tamoxifen among premenopausal women diagnosed with ER-positive breast cancer in 1999, the risk of recurrence decreased by nearly one-half (OR = 0.52), consistent with evidence from clinical trials; however, the estimate was imprecise (95% confidence interval [CI] = 0.25, 1.85). We observed an imprecise association between tamoxifen use and recurrence from the time it was introduced in 1982 (OR = 1.24 95% CI = 0.46, 5.11), inconsistent with prior knowledge from clinical trials. For the introduction of trastuzumab in 2007, the estimate was also consistent with trial evidence, though imprecise (OR = 0.51; 95% CI = 0.21, 22.4). CONCLUSIONS: We demonstrated how novel pharmacoepidemiologic analytic designs can be used to evaluate the routine clinical care and effectiveness of therapeutic advancements in a population-based setting while considering some limitations of the approach.

Sacituzumab Govitecan in patients with breast cancer brain metastases and recurrent glioblastoma: a phase 0 window-of-opportunity trial.

Sacituzumab Govitecan (SG) is an antibody-drug conjugate that has demonstrated efficacy in patients with TROP-2 expressing epithelial cancers. In a xenograft model of intracranial breast cancer, SG inhibited tumor growth and increased mouse survival. We conducted a prospective window-of-opportunity trial (NCT03995706) at the University of Texas Health Science Center at San Antonio to examine the intra-tumoral concentrations and intracranial activity of SG in patients undergoing craniotomy for breast cancer with brain metastases (BCBM) or recurrent glioblastoma (rGBM). We enrolled 25 patients aged ≥18 years diagnosed with BCBM and rGBM to receive a single intravenous dose of SG at 10 mg/kg given one day before resection and continued on days 1 and 8 of 21-day cycles following recovery. The PFS was 8 months and 2 months for BCBM and rGBM cohorts, respectively. The OS was 35.2 months and 9.5 months, respectively. Grade≥3 AE included neutropenia (28%), hypokalemia (8%), seizure (8%), thromboembolic event (8%), urinary tract infection (8%) and muscle weakness of the lower limb (8%). In post-surgical tissue, the median total SN-38 was 249.8 ng/g for BCBM and 104.5 ng/g for rGBM, thus fulfilling the primary endpoint. Biomarker analysis suggests delivery of payload by direct release at target site and that hypoxic changes do not drive indirect release. Secondary endpoint of OS was 35.2 months for the BCBM cohort and 9.5 months for rGBM. Non-planned exploratory endpoint of ORR was 38% for BCBM and 29%, respectively. Exploratory endpoint of Trop-2 expression was observed in 100% of BCBM and 78% of rGBM tumors. In conclusion, SG was found to be well tolerated with adequate penetration into intracranial tumors and promising preliminary activity within the CNS. Trial Registration: Trial (NCT03995706) enrolled at Clinical Trials.gov as Neuro/Sacituzumab Govitecan/Breast Brain Metastasis/Glioblastoma/Ph 0: https://clinicaltrials.gov/study/NCT03995706?cond=NCT03995706 .

Recurrences after nephron-sparing treatments of renal cell carcinoma: a competing risk analysis.

PURPOSE: To examine associations between ablative therapy (AT) and partial nephrectomy (PN) and the occurrence of local recurrence (LR), distant metastatic recurrence (DMR) and all-cause mortality in a nation-wide real-world population-based cohort of patients with nonmetastatic renal cell carcinoma (nmRCC). METHODS: Data on 2751 AT- or PN-treated nmRCC tumours diagnosed during 2005-2018, representing 2701 unique patients, were obtained from the National Swedish Kidney Cancer Register. Time to LR/DMR or death with/without LR/DMR was analysed using Cox regression models. RESULTS: During a mean of 4.8 years follow-up, LR was observed for 111 (4.0%) tumours, DMR for 108 (3.9%) tumours, and death without LR/DMR for 206 (7.5%) tumours. AT-treated tumours had a 4.31 times higher risk of LR (P < 0.001) and a 1.91 times higher risk of DMR (P = 0.018) than PN-treated, with no significant differences in risk of death without LR/DMR. During a mean of 3.2 and 2.5 years of follow-up after LR/DMR, respectively, 24 (21.6%) of the LR cases and 56 (51.9%) of the DMR cases died, compared to 7.5% in patients without LR/DMR. There were no significant differences between AT- and PN-treated regarding risks of early death after occurrence of LR or DMR. CONCLUSION: AT treatment of patients with nmRCC implied significantly higher risks of LR and DMR compared with PN treatment. To minimize the risks of LR and DMR, these results suggest that PN is preferred over AT as primary treatment, supporting the EAU guidelines to recommended AT mainly to frail and/or comorbid patients.

Total mesorectal excision quality in rectal cancer surgery affects local recurrence rate but not distant recurrence and survival: population-based cohort study.

BACKGROUND: The quality of the total mesorectal excision specimen in rectal cancer surgery is assessed with a three-tier grade (mesorectal, intramesorectal and muscularis propria). This study aimed to analyse the prognostic impact of the total mesorectal excision grade on survival, and to identify risk factors for intramesorectal and muscularis propria resection in a population-based setting. METHODS: All patients in the Swedish Colorectal Cancer Registry with rectal cancer stage I-III ≤ 10 cm from the anal verge, diagnosed 2015-2019, undergoing total mesorectal excision were analysed. Clinical, surgical and pathological data were retrieved and analysed for the following primary outcomes: local and distant recurrence and overall and relative survival; secondary outcomes were risk factors for total mesorectal excision grading (intramesorectal or muscularis propria resection). Of note, postoperative death < 30 days or recurrence within 90 days were exclusion criteria for survival and recurrence analysis. Recurrence-free patients with less than 3 years follow-up, and patients lacking data regarding recurrence, were also excluded from recurrence analyses. RESULTS: Overall, of 7979 patients treated during the study interval, 1499 patients were eligible for recurrence, 2441 patients for survival and 2476 patients for risk-factor analyses, of which 75% were graded mesorectal, 17% intramesorectal and 8% muscularis propria. Median follow-up for survival was 42 (1-77) months. The worst total mesorectal excision grading (muscularis propria resection) was an independent risk factor for local recurrence in multivariable analysis (HR 2.73, 95% c.i. 1.07 to 7.0, P = 0.036). Total mesorectal excision grade had no impact on distant recurrence or survival. Female sex, tumour level <5 cm, abdominoperineal resection, minimally invasive surgery (laparoscopic and robotic), high blood loss, long duration of surgery and intraoperative perforation were independent risk factors for worse total mesorectal excision grading (intramesorectal and/or muscularis propria resection) in multivariable analyses. CONCLUSION: Muscularis propria resection increases the risk of local recurrence but does not seem to affect distant recurrence or survival.

No difference in oncological outcomes and perioperative complications between patients with ESRD with unilateral and bilateral UTUC receiving radical nephroureterectomy.

Patients with end stage renal disease (ESRD) are at high risk of developing upper tract urothelial carcinoma (UTUC). Due to high recurrence rate of UTUC in contralateral kidney and ureter, and high risk of complications related to surgery and anesthesia, whether it's necessary to remove both kineys and ureters at one time remains in debate. We utilized Taiwanese UTUC Registry Database to valuate the difference of oncological outcomes and perioperative complications between patients with ESRD with unilateral and bilateral UTUC receiving surgical resection. Patients with ESRD and UTUC were divided into three groups, unilateral UTUC, previous history of unilateral UTUC with metachronous contralateral UTUC, and concurrent bilatetral UTUC. Oncological outcomes, perioperative complications, and length of hospital stays were investiaged. We found that there is no diffence of oncological outcomes including overall survival, cancer specific survival, disease free survival and bladder recurrence free survival between these three groups. Complication rate and length of hospital stay are similar. Adverse oncological features such as advanced tumor stage, lymph node involvement, lymphovascular invasion, and positive surgical margin would negatively affect oncological outcomes.

Follow-up analysis and research of very low-risk and low-risk gastrointestinal stromal tumors after endoscopic resection.

Currently, due to limited long-term evidence, there remains some controversy surrounding the recommended postoperative monitoring strategy for primary low-risk gastrointestinal stromal tumors (GISTs). This study recruited a total of 532 patients diagnosed with very low-risk and low-risk GISTs who underwent endoscopic resection from 2015 to 2021, including 460 very low-risk patients and 72 low-risk patients. Descriptive statistical analysis was used to evaluate the clinical and pathological characteristics of GIST patients, and Kaplan-Meier methods were employed for survival analysis. The results showed that the 5-year recurrence-free survival rates for very low-risk and low-risk patients were 98.5% and 95.9%, respectively. The 5-year disease-specific survival rates for both groups were 100%. Additionally, the 5-year overall survival rates were 99.7% for very low-risk patients and 100% for low-risk patients (P = 0.69). Therefore, it is suggested that routine follow-up monitoring, including endoscopic surveillance and imaging, may not be necessary for very low-risk and low-risk GISTs after endoscopic resection.

Failure patterns and individualized treatment plans of reirradiation for inoperable locally recurrent nasopharyngeal carcinoma.

Re-irradiation with intensity-modulated radiotherapy (IMRT) remains the primary treatment modality for inoperable locally recurrent nasopharyngeal carcinoma (NPC). However, the rate of radiation-related late adverse effects is often substantially high. Therefore, we aimed to explore failure patterns and individualized treatment plans of re-irradiation for inoperable locally recurrent NPC. Ninety-seven patients who underwent IMRT were retrospectively analyzed. Sixty-two patients had clinical target volume of recurrence (rCTV) delineated, and thirty-five patients had only gross tumor volume of recurrence (rGTV) delineated. Twenty-nine patients developed second local failures after re-irradiation with IMRT (28 cases available). Among those patients, 64.3% (18/28) of patients and 35.7% (10/28) developed in-field or out-field, respectively. No statistical correlation was observed between target volume (rGTV or rCTV) and the local recurrence rate, local failure patterns, grade ≥ 3 toxicity, and survival. Multivariate analysis showed that recurrent T (rT) stage (HR 2.62, P = 0.019) and rGTV volume (HR 1.73, P = 0.037) were independent prognostic factors for overall survival (OS). Risk stratification based on rT stage and rGTV volume revealed that low risk group had a longer 3-year OS rate (66.7% vs. 23.4%), lower total grade ≥ 3 toxicity (P = 0.004), and lower re-radiation associated mortality rates (HR 0.45, P = 0.03) than high risk group. This study demonstrates that the delineation of rCTV may not be beneficial for re-irradiation using IMRT in locally recurrent NPC. Patients with low risk were most suitable for re-irradiation, with maximizing local salvage and minimizing radiation-related toxicities. More precise and individualized plans of re-irradiation are warranted.

Endonasal endoscopic or endoscopic-assisted transcranial surgery of Rathke's cleft cysts: does the approach and surgical technique influence the radicality and recurrence rate?

OBJECTIVE: Resections of symptomatic Rathke's cleft cysts (RCCs) are mainly performed via an endonasal transsphenoidal approach. However, there is a lack of equivalent data in current literature concerning transcranial keyhole approach in the treatment of RCCs. In order to find general recommendations for the surgical treatment of RCCs also with regard to recurrence, the object of this study is the analysis and comparison of both techniques. METHODS: Twenty-nine patients having been surgically treated between January 2004 and August 2019 were retrospectively analysed. The transsphenoidal approach was chosen in 16 cases and the transcranial keyhole approach in 13 cases. Both surgical techniques were analyzed and compared concerning preoperative symptoms and cyst characteristics, complications, surgical radicality, endocrinological and ophthalmological outcome and recurrences in patients´ follow up. RESULTS: The postoperative outcome of both techniques was identic and showed highly satisfying success rates with 92% for neurological deficits, 82% for endocrinological dysfunctions and 86% for visual deficits. In contrast, momentous postoperative complications were significantly more likely after transsphenoidal operations. After a mean follow-up time of 5.7 years, the recurrence rates of both cohorts were the same with 0% each. CONCLUSIONS: Regarding its equal outcome with its lower complication rate, the authors suggest using the supraorbital keyhole approach for RCCs whose anatomical configuration allow both techniques. Yet, the decision should always consider the surgeon's personal experience and other individual patient characteristics. Further studies with higher numbers of cases and longer follow-up periods are necessary to analyse the effect of the selected approach on recurrence.

Recurrence in Eyelid Sebaceous Carcinoma: A Multicentric Study of 418 Patients.

Purpose: Local recurrence predicts dismal prognosis in eyelid sebaceous carcinoma (SC). Recurrence predictors vary across studies. Accurate recurrence estimation is essential for individualized therapy in eyelid SC. This study aims to identify recurrence predictors and develop a nomogram for personalized prediction in eyelid SC. Methods: We conducted a multicenter retrospective cohort study. Chart reviews were performed in 418 consecutive patients with eyelid SC. All patients were followed up after their initial surgery. Multivariate Cox regression was used to explore the independent predictors of recurrence. A nomogram for recurrence prediction was developed and validated with bootstrap resampling. The predictive accuracy and discriminative ability were compared with the Tumor, Node, Metastasis (TNM) staging system. Results: Over a median of 60-month follow-up, 167 patients (40%) had local recurrence. The median time from diagnosis to recurrence was 14 months. The 1-year cumulative recurrence rate was 18%. Diagnostic delay (hazard ratio [HR] = 1.01, 95% confidence interval [CI] = 1.00-1.01, P = 0.001), orbital involvement (HR = 4.47, 95% CI = 3.04-6.58, P < 0.001), Ki67 (HR = 1.01, 95% CI = 1.00-1.02, P = 0.008) and initial surgery of Mohs micrographic surgery with intraoperative frozen section control (HR = 0.53, 95% CI = 0.35-0.80, P = 0.003) were independent influencing factors of recurrence. A nomogram integrating these four factors combined with pagetoid spread displayed satisfactory discriminative ability (C-index = 0.80-0.83; area under the curve [AUC] = 0.82-0.84), which compared favorably than TNM staging (all P < 0.05). Conclusions: The recurrence rate is high in eyelid SC. Early detection and primary resection with Mohs micrographic surgery are recommended in controlling recurrence. Patients with orbital involvement, high Ki67 expression, and pagetoid spread may require adjuvant measures. This nomogram offers more accurate recurrence estimates, aiding in therapeutic decision making.

Predicting recurrent glioblastoma clinical outcome to immune checkpoint inhibition and low-dose bevacizumab with tumor in situ fluid circulating tumor DNA analysis.

OBJECTIVE: Most recurrent glioblastoma (rGBM) patients do not benefit from immune checkpoint inhibition, emphasizing the necessity for response biomarkers. This study evaluates whether tumor in situ fluid (TISF) circulating tumor DNA (ctDNA) could serve as a biomarker for response to low-dose bevacizumab (Bev) plus anti-PD-1 therapy in rGBM patients, aiming to enhance systemic responses to immunotherapy. METHODS: In this phase II trial, 32 GBM patients with first recurrence after standard therapy were enrolled and then received tislelizumab plus low-dose Bev each cycle. TISF samples were analyzed for ctDNA using a 551-gene panel before each treatment. RESULTS: The median progression-free survival (mPFS) and overall survival (mOS) were 8.2 months (95% CI, 5.2-11.1) and 14.3 months (95% CI, 6.5-22.1), respectively. The 12-month OS was 43.8%, and the objective response rate was 56.3%. Patients with more than 20% reduction in the mutant allele fraction and tumor mutational burden after treatment were significantly associated with better prognosis compared to baseline TISF-ctDNA. Among detectable gene mutations, patients with MUC16 mutation, EGFR mutation & amplification, SRSF2 amplification, and H3F3B amplification were significantly associated with worse prognosis. CONCLUSIONS: Low-dose Bev plus anti-PD-1 therapy significantly improves OS in rGBM patients, offering guiding significance for future individualized treatment strategies. TISF-ctDNA can monitor rGBM patients' response to combination therapy and guide treatment. CLINICAL TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, NCT05540275.

Anlotinib reversed resistance to PD-1 inhibitors in recurrent and metastatic head and neck cancers: a real-world retrospective study.

Patients with recurrent or metastatic head and neck cancers (R/M HNCs) are prone to developing resistance after immunotherapy. This retrospective real-world study aims to investigate whether the addition of anlotinib can reverse resistance to PD-1 inhibitors (PD-1i) and evaluate the efficacy and safety of this combination in R/M HNCs. Main outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. Potential biomarkers included PD-L1 expression, lipid index, and genomic profiling. Twenty-one patients with R/M HNCs were included, including 11 nasopharyngeal carcinoma (NPC), five head and neck squamous cell carcinoma (HNSCC), three salivary gland cancers (SGC), and two nasal cavity or paranasal sinus cancers (NC/PNC). Among all patients, ORR was 47.6% (95% CI: 28.6-66.7), with 2 (9.5%) complete response; DCR was 100%. At the median follow-up of 17.1 months, the median PFS and OS were 14.3 months (95% CI: 5.9-NR) and 16.7 months (95% CI:8.4-NR), respectively. The median DOR was 11.2 months (95% CI: 10.1-NR). As per different diseases, the ORR was 45.5% for NPC, 60.0% for HNSCC, 66.7% for SGC, and 50.0% for NC/PNC. Most treatment-related adverse events (TRAEs) were grade 1 or 2 (88.9%). The most common grades 3-4 TRAE was hypertension (28.6%), and two treatment-related deaths occurred due to bleeding. Therefore, adding anlotinib to the original PD-1i could reverse PD-1 blockade resistance, with a favorable response rate, prolonged survival, and acceptable toxicity, indicating the potential as a second-line and subsequent therapy choice in R/M HNCs.

Outcomes of Low-Risk Differentiated Thyroid Cancer (DTC) without Radioactive Iodine (RAI) Ablation Therapy Post-Thyroidectomy: An Experience from a Tertiary Centre in Karachi.

OBJECTIVE: To assess the outcomes of low-risk differentiated thyroid cancer (DTC) with tumour size 1 to 4 cm post-thyroidectomy in patients who never received radioactive iodine (RAI) ablation and to compare the outcomes with those who received RAI therapy. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Nuclear Medicine, Karachi Institute of Radiotherapy and Nuclear Medicine (KIRAN) Hospital, Karachi, Pakistan, from January 2016 to December 2020. METHODOLOGY: A total of 130 consecutive patients of low-risk DTC of both genders aged between 18-75 years were identified who underwent thyroidectomy. Patients were classified as either being treated or not treated with RAI, based on RAI data post-thyroidectomy. Patients were followed up for two to five years depending on their date of diagnosis from 2016 to 2020, using thyroglobulin (Tg), anti-thyroglobulin (anti-Tg), and thyrotropin (TSH) levels and ultrasound neck. Association between patients who received RAI and who did not receive RAI was determined and a p-value <0.05 was considered as statistical significance. RESULTS: Patients had mean age of 34.5 ± 10.4 years with majority of females (75.4%). Majority of the patients (94.6%) had total thyroidectomy with no neck dissection (83.1%). RAI therapy was conducted among 70.8% participants, of which, 56.9% participants received a dose of 100 mci. Most of the patients had positive outcomes as there was no recurrence among 96.2% participants. There was a significant difference in RAI therapy with total thyroidectomy as compared to subtotal, RAI dose, tumour stage, neck dissection, and lymph node involvement (p ≤0.001). CONCLUSION: After complete tumour resection, a highly selected group of patients with low-risk local disease have shown low rate of recurrence when managed without RAI. Interestingly, the disease recurrence was also only seen in patients who received RAI therapy in comparison to those who did not receive RAI therapy. KEY WORDS: Outcomes, Differentiated thyroid cancer, Radioactive iodine, Ablation therapy, Post-surgery.

Electron beam radiotherapy for the management of squamous cell carcinoma of the anal margin.

PURPOSE AND OBJECTIVE: Squamous cell carcinoma of the anal margin (SCCAM) is an uncommon lesion that comprises one-third to a quarter of all anal squamous cell carcinoma. Treatment involves surgery or exclusive radiotherapy for small tumours, whereas the preferred treatment for larger tumours is chemoradiotherapy. In our department, selected patients with SCCAM are treated with electron beam radiotherapy using one perineal field. The present study evaluates this strategy. MATERIAL AND METHODS: All consecutive patients with SCCAM and treated with electron beam radiotherapy from 2012 to 2022 were included. Data were retrospectively extracted from the medical records and analysed descriptively. Local control (LC) and overall survival (OS) were analysed using Kaplan-Meier statistics. RESULTS: Forty patients were evaluated. Primary radiotherapy was delivered in 35 (87.5%) patients. Five (12.5%) patients had postoperative radiotherapy. Median prescription dose was 60.0 (range 45.0-60.2) Gy in 28 (range 10-30) fractions delivered with 8 (range 4-18) MeV using a standard circular aperture and bolus. At a median follow-up of 73 (range 9-135) months, 7 (17.5%) patients were diagnosed with local recurrences. The 5-year LC rate was 84.3% (95% CI: 71.4%-97.2%). Analysis of LC according to T-stage revealed a 5-year LC of 100% (95% CI: 100%-100%) in T1 tumours compared to 57.0% (95% CI: 27.4%-86.6%) in T2 tumours (p < 0.001). 5-year OS was 91.6% (95% CI: 83.0%-100%). Late grade 3 toxicity included ulceration in the skin and subcutis in 2 (5.0%) patients. INTEPRETATION: Electron beam radiotherapy enables the delivery of 'eye-guided' radiotherapy directly to the tumour. LC is good in patients with T1 tumours. Patients with T2 tumours have less satisfactory LC and should be treated with chemoradiotherapy. Electron beam radiotherapy enables the delivery of "eye-guided" RT directly to the tumour. LC is excellent in patients with T1 tumours. Patients with T2 tumours have less satisfactory LC and should be treated with chemoradiotherapy.

Immunohistochemical Profile of p62/SQSTM1/Sequestosome-1 in Human Low- and High-Grade Intracranial Meningiomas.

Among autophagic-related proteins, p62/SQSTM1/Sequestosome-1 represents a relevant actor in cellular proliferation and neoplastic growth. Although, recently, p62 expression has been analyzed in different neurodegenerative and glial neoplastic diseases, no available information have been reported in meningiomas, which have an high epidemiological relevance being the second most common category of intracranial tumors after gliomas. Generally meningiomas have a benign behavior, but their recurrence is not uncommon mainly when atypical or anaplastic varieties occur. However, intranuclear vacuoles have been ultrastructurally observed in meningiomas, and they were labelled by p62 antibodies. Therefore, in the present study, we have investigated p62 immunohistochemical pattern in a cohort of 133 cases representative of low- and high-grade meningiomas, to verify if p62 expression may be related to clinicopathological data, thus achieving a potential prognostic role. The p62 immunoexpression was frequently found in the nucleus and cytoplasm of neoplastic elements, and utilizing an intensity-distribution score, 55 (41.3%) cases were considered as high expressors while 78 (58.7%) cases were instead recorded as low expressors. Fifteen cases exhibited recurrences of the disease, 14 of which were codified as high expressors. Moreover, a direct relationship between p62 and Mib-1 immunoexpression as well as between p62 and neoplastic grade have been documented. Finally, we suggest that impaired autophagic flux with an increase in p62 expression may be involved in the activation of NRF2 also contributing in the development of recurrence in meningioma patients.

Three-dimensional imaging of upper tract urothelial carcinoma improves diagnostic yield and accuracy.

Upper tract urothelial carcinoma (UTUC) is a rare form of urothelial cancer with a high incidence of recurrence and a low survival rate. Almost two-thirds of UTUCs are invasive at the time of diagnosis; therefore, improving diagnostic methods is key to increasing survival rates. Histopathological analysis of UTUC is essential for diagnosis and typically requires endoscopy biopsy, tissue sectioning, and labeling. However, endoscopy biopsies are minute, and it is challenging to cut into thin sections for conventional histopathology; this complicates diagnosis. Here, we used volumetric 3-dimensional (3D) imaging to explore the inner landscape of clinical UTUC biopsies, without sectioning, revealing that 3D analysis of phosphorylated ribosomal protein S6 (pS6) could predict tumor grade and prognosis with improved accuracy. By visualizing the tumor vasculature, we discovered that pS6+ cells were localized near blood vessels at significantly higher levels in high-grade tumors than in low-grade tumors. Furthermore, the clustering of pS6+ cells was associated with shorter relapse-free survival. Our results demonstrate that 3D volume imaging of the structural niches of pS6 cells deep inside the UTUC samples improved diagnostic yield, grading, and prognosis prediction.