Disease Recurrence In Patients Research Articles

Disease recurrence in patients undergoing mastectomy for ductal carcinoma in situ.

With DCIS incidence on the rise, up to 30% of patients undergo mastectomy for Ductal carcinoma in situ (DCIS) (Nash and Hwang, in: Ann Surg Oncol 30(6):3206-3214, 2023). Local recurrence rates after mastectomy for DCIS are reportedly low, but risk factors for recurrence are not known (Kim et al., in: J Cancer Res Ther 16(6):1197-1202, 2020). We aim to define risk factors associated with ipsilateral breast cancer recurrence in patients undergoing mastectomy for DCIS. We aimed to identify risk factors that may contribute to recurrence of breast cancer following mastectomy for pure DCIS. We hypothesized that close or positive mastectomy margins, age at diagnosis, extent of breast disease and mutation carriers would be associated with increased risk of recurrence. We performed a retrospective chart review of patients who underwent unilateral or bilateral mastectomies for pure DCIS at a single academic tertiary referral center from 2013 to 2023. There were 165 patients who met inclusion criteria with an average length of follow-up of 39.9months. On final surgical pathology, the average span of DCIS was 33.7mm (± 24.6mm). Hormone receptor positive disease was identified in 80.6% of the patient cohort. For margin status, 23 patients (14%) had < 1mm margins on final pathology and of those, 1 received adjuvant radiation therapy and 4 returned to the OR for re-excision. Only 1 (0.6%) patient had ipsilateral disease recurrence during the study period. Recurrence after mastectomy for pure DCIS is a rare event and in our study sample, only one recurrence occurred. Risk factors for recurrence appear unrelated to margin status, age, extent of DCIS, or pathogenic mutation (ElSherif et al., in Am J Surg 226(5):646-651, 2023).

Real-world perioperative treatment patterns and burden of recurrent disease in patients with high-risk endometrial cancer: a SEER-Medicare study

Objectives To elucidate unmet needs in high-risk endometrial cancer (EC), this study described perioperative treatment patterns in Medicare beneficiaries with high-risk EC and quantified the impact of disease recurrence on clinical and economic outcomes among patients receiving adjuvant therapy. Methods Patients aged ≥66 years with high-risk EC (stage I/II EC of non-endometrioid histology or stage III/IVA EC of any histology) receiving hysterectomy with bilateral salpingo-oophorectomy from SEER-Medicare data (2007–2019) were identified; perioperative treatment patterns were described. Post-operative treatment patterns were described among patients receiving adjuvant therapy; overall survival (OS), all-cause and EC-related healthcare resource utilization and costs were evaluated from recurrence date (using a claims-based algorithm developed with clinical input) for recurrent patients and from a frequency-matched date for non-recurrent patients. Results Of 2,279 patients receiving EC surgery, 3.1% received neoadjuvant therapy and 55.3% received adjuvant therapy. Among 1,199 patients receiving adjuvant therapy, systemic adjuvant therapy with radiation (38.9%) was most common. Median OS was 1.4 years among 378 (31.5%) recurrent patients identified over a median follow-up of 3.7 years. Recurrent patients had significantly higher per-patient-year rates of all-cause outpatient visits (37.7 vs. 22.6), EC-related outpatient visits (14.5 vs. 3.0), and all-cause hospitalizations (1.3 vs. 0.4) than non-recurrent patients, and an excess of $84,562 and $62,128 in all-cause and EC-related annual costs, predominantly driven by hospitalizations. Conclusions Our findings highlight the considerable clinical and economic burden experienced by patients with high-risk EC experiencing recurrence and emphasize the unmet need for novel therapies in early settings to mitigate this burden.

B-085 Optimizing Thyroglobulin Antibody Interference Thresholds to Minimize Turn-around Time

Abstract Background Serum thyroglobulin (Tg) is a key biomarker used to detect disease recurrence in patients with differentiated thyroid cancers who have undergone complete thyroidectomy. Thyroglobulin antibodies (TgAb) can interfere with accurate measurement of serum Tg levels, producing falsely low results in automated immunoassays. Thus before measurement of Tg, TgAb levels are measured to determine if in-house immunoassays can be used or if the patient’s sample will need to be sent out for radioimmunoassay (RIA) or mass spectrometry methodologies, which are less sensitive to TgAb interference. We recently transitioned to new instrumentation and noted a sharp increase in Tg samples with TgAb interference that needed to be sent out when we used the limit of detection (LOD) of the Roche TgAb assay. This increases turnaround times for patients and increases laboratory costs. We hypothesized that the LOD of the Roche TgAb assay is below the level of interference in Tg immunoassays. To test this we compared the performance of TgAb immunoassays (IA) and Tg measurements by IA and RIA with the intention of proposing a more appropriate threshold for TgAb interference for the Roche TgAb assay. Methods We collected 121 serum specimens, which were above the LOD of the Roche TgAb (R-TgAb) assay, which is 10 IU/mL. These specimens were sent as part of standard care to USC for measurement of TgAb by Kronus (K-TgAb) and Tg by RIA. On these split samples we also measured Tg by Beckman Access (B-Tg). We compared the detection of TgAb by USC to varying thresholds of Roche TgAb measurements (10 IU/mL [LOD], 20 IU/mL, and 115 IU/mL [reference interval for autoimmunity]), and assessed the agreement between Tg measurements by Beckman IA and USC RIA for different Roche TgAb thresholds. Analyses were performed in Prism Graphpad using linear regression. Results Qualitatively, the concordance for R-TgAb to RIA (reference) at 10 IU/mL was 31%, at 20 IU/mL was 90%, and at 115 IU/mL was 80%. Quantitative agreement between the B-Tg immunoassay and RIA for the TgAb thresholds of: TgAb &amp;gt;10 IU/mL gave an R2=0.97 for Tg comparison, &amp;gt;20 IU/mL gave an R2=0.99, and &amp;gt;115 IU/mL R2=0.99. Conclusions Prior studies have shown that TgAb immunoassays can produce significant qualitative and quantitative differences. In our study, we attempt to validate the use of the Roche immunoassay with a cutoff of 20 IU/mL to minimize interference between Tg and TgAb in order to accurately detect recurrence of thyroid cancer. We found that a TgAb cutoff of 20 IU/mL we maintained acceptable agreement between Tg methods indicating no significant interference up to 20 IU/mL. With the TgAb cutoff of 20 IU/mL, we would be able to reduce sendouts for this cohort from 121 to 42, reducing sendouts by 65% and allowing a faster turnaround time for a significant proportion of our patients.

Pattern of Failure in Patients with Biochemical Recurrence After PSMA Radioguided Surgery.

Prostate-specific membrane antigen (PSMA)-targeted radioguided surgery (RGS) is evolving as a new treatment modality for patients with early biochemical recurrence of prostate cancer and disease limited to locoregional lymph nodes on PSMA-ligand PET/CT. Nevertheless, the pattern of failure (locoregional vs. systemic) after PSMA RGS remains unknown. Therefore, the aim of this retrospective analysis was to evaluate the pattern of disease using PSMA-ligand PET in patients experiencing relapse after PSMA RGS. Methods: We evaluated 100 patients with biochemical recurrence after previous PET-guided PSMA RGS who underwent PSMA-ligand PET (median prostate-specific antigen [PSA], 0.9 ng/mL; range, 0.2-14.2 ng/mL). All suspicious lesions for recurrent prostate cancer were grouped according to the molecular imaging TNM classification system. Detection rates and lesion localization were determined and stratified by PSA values and the International Society of Urological Pathology grade group. Further, lesion localization was compared before and after PSMA RGS. Results: The median time between PSMA RGS and PSMA-ligand PET for relapse was 11.4 mo (range, 5.5-25.6 mo). In total, 91 of 100 (91%) patients showed PSMA-ligand-positive findings. PSMA PET detection rates were 82.6%, 92.6%, 91.3%, and 96.3% for PSA levels of 0.2-0.49, 0.5-0.99, 1-1.99, and at least 2 ng/mL, respectively. More than half of the patients (53%; 48/91) showed local recurrence or pelvic lymph node metastases only. Extrapelvic lymph node metastases, bone metastases, and visceral metastases were present in 22% (20/91), 16% (15/91), and 9% (8/91) of the patients, respectively. With increasing International Society of Urological Pathology grade group, the percentage of patients with bone and visceral metastases increased, whereas the number of patients with only locoregional disease decreased. Conclusion: PSMA-ligand PET is a useful method to detect and localize recurrent disease in patients with biochemical failure after PSMA RGS, with more than half of the patients presenting with locoregional recurrence, offering the potential for a second local therapy (e.g., radiation therapy or repeated surgery).

Impact of postsurgical vaginal microbiome on high-risk HPV infection and recurrence risk in patients with cervical cancer and intraepithelial neoplasia: A retrospective study

PurposeThis study aimed to determine the effect of postsurgical vaginal microbiome (VM) on high-risk human papillomavirus (hrHPV) infection and the risk of disease recurrence in patients surgically treated for cervical cancer (CC) or intraepithelial neoplasia (CIN). Methods207 women who underwent surgical treatment for CC or CIN at the Department of Gynecologic Oncology of the First Affiliated Hospital of University of Science and Technology of China from November 2016 to October 2023 were included. The patients’ clinical data, including age, surgical modality, and diagnosis at time of index surgery, were collected retrospectively and analyzed. Associations between postsurgical VM indices, hrHPV infection, cervical cytology, and recurrence were also evaluated. ResultsPatient age, surgical modality (whether complete excision of the cervix was performed), and diagnosis at time of index surgery (cervical dysplasia vs. cervical carcinoma) showed no significant association with postsurgical hrHPV infection, cervical cytology, or disease recurrence. However, postsurgical VM imbalance was significantly associated with hrHPV infection status (OR = 4.640, 95 % CI = 2.085–10.460, P < 0.001), abnormal cervical cytology (OR = 3.994, 95 % CI = 1.154–13.826, P = 0.020), and disease recurrence (OR = 3.789, 95 % CI = 1.091–13.154, P = 0.026). Among the specific VM indices, a vaginal pH above 4.5 (OR = 4.570, 95 % CI = 1.640–12.690, P = 0.002), a lactobacilli proportion below 50 % (OR = 3.938, 95 % CI = 1.299–11.934, P = 0.010), and the presence of aerobic vaginitis (AV, OR = 2.425, 95 % CI = 0.996–5.901, P = 0.046) were risk factors for postsurgical recurrence. ConclusionPostsurgical VM imbalance, especially abnormal indices, such as a pH above 4.5, a lactobacilli proportion below 50 %, and the presence of AV, was associated with an increased risk of postsurgical recurrence in patients who underwent surgical treatment for CIN and CC. Monitoring and potentially intervening in the VM may improve the prognosis of these patients.

Match Point: Nuclear Medicine Imaging for Recurrent Thyroid Cancer in TENIS Syndrome-Systematic Review and Meta-Analysis.

Background/Objectives: Disease recurrence and resistance to radioiodine (RAI) therapy are major challenges in the management of differentiated thyroid cancer (DTC). In particular, the TENIS (Thyroglobulin Elevated Negative Iodine Scintigraphy) syndrome, characterised by elevated thyroglobulin (Tg) serum levels in addition to a negative radioiodine whole body scan (WBS), complicates disease monitoring and treatment decisions. Conventional imaging techniques often fail to detect disease in WBS-negative patients with rising Tg levels, leading to limitations in therapeutic intervention. This systematic review and meta-analysis aims to evaluate the diagnostic accuracy of nuclear imaging modalities in detecting disease recurrence in patients with the TENIS syndrome and to provide insights to guide therapeutic approaches in this complex clinical scenario. Methods: A comprehensive search of PubMed/MEDLINE and EMBASE databases up to March 2024 was performed according to PRISMA guidelines. Eligible studies were selected, and quality assessment was performed with the QUADAS-2 tool. For each study, relevant data were extracted and synthesised. A meta-analysis of the diagnostic accuracy of [18F]FDG PET/CT was performed, and patient-based pooled sensitivity and specificity were calculated using a random-effects model. Statistical heterogeneity between studies was assessed using the I2 statistic. Results: Of the 538 studies initially identified, 22 were included in the systematic review, of which 18 were eligible for meta-analysis. The eligible studies, mainly focused on [18F]FDG PET/CT, showed variable sensitivity and specificity for the detection of RAI-refractory thyroid cancer lesions. For [18F]FDG PET/CT, pooled estimates displayed a sensitivity of 0.87 (95% CI: 0.82-0.90) and a specificity of 0.76 (95% CI: 0.61-0.86), with moderate heterogeneity between studies. Conclusions: [18F]FDG PET/CT remains central in the detection of disease recurrence in patients with the TENIS syndrome. The emergence of novel radiopharmaceuticals with specific molecular targets is a promising way to overcome the limitations of [18F]FDG in these patients and to open new theranostics perspectives. This review highlights the great potential of nuclear medicine in guiding therapeutic strategies for RAI-refractory thyroid cancer.

Diagnostic performance of 2-[18F]FDG PET/CT in recurrent differentiated thyroid cancer and elevated antithyroglobulin antibodies: an updated systematic review and bivariate meta-analysis.

This updated systematic review and bivariate meta-analysis aimed to investigate the diagnostic performance of 2-[18F]FDG PET/CT for the detection of recurrent disease in patients with differentiated thyroid cancer (DTC) who have negative 131I whole body scintigraphy and increased antithyroglobulin antibodies (TgAb) levels. The current systematic review was carried out following a preset protocol, and the "Preferred Reporting Items for a Systematic Review and Meta-Analysis" served as a guideline for its development and reporting. A comprehensive research of the PubMed/MEDLINE, Embase and Cochrane library databases was conducted until June 2024. Between 2002 and 2023, 13 studies (608 patients) published on this topic were selected. The pooled sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 2-[18F]FDG PET or PET/CT were 84% (95%CI: 78-87%), 82% (95%CI: 78-86%), 72% (95%CI: 67-76%), 90% (95%CI: 87-93%) and 83% (95%CI: 79%-86%) respectively. The pooled positive and negative likelihood ratios (LR+ and LR - ) and the diagnostic odds ratio (DOR) were 0.180 (95%CI: 0.128-0.253), 3.214 (95%CI: 2.357-4.383), and 17.863 (95%CI: 10.475-30.462), respectively. No statistically significant heterogeneity among the studies was found for all the metrics evaluated (I2 < 50%). 2-[18F]FDG PET/CT demonstrated a good diagnostic performance in patients with DTC and increased TgAb. Although more studies are warranted, the provided evidence-based data should support the integration of 2-[18F]FDG PET/CT in clinical and diagnostic guidelines on DTC patients with increased TgAb.

De novo and recurrent post-transplant membranous nephropathy cases show similar rates of concurrent antibody-mediated rejection.

Membranous nephropathy (MN) can develop post-kidney transplant and is classified as a recurrent disease in patients with a history of MN in the native kidneys or as de novo disease in patients without such history. The mechanism of recurrent MN is thought to be like that of primary MN, but the mechanism of de novo MN is not well delineated. An association between de novo MN and antibody-mediated rejection (AMR) has been suggested. A search of the pathology database from our medical center identified 11 cases of recurrent and 15 cases of de novo MN, in which clinical and histologic findings were compared. No significant differences were identified in the demographic characteristics, serum creatinine and proteinuria trends, or rates of allograft failure between the recurrent and de novo MN groups. Rates of concurrent AMR were high in both groups (36% and 40%, respectively) but not statistically different from each other. PLA2R immunofluorescence (IF) positivity was seen in 64% of recurrent MN cases compared to 33% of de novo MN cases, suggesting a higher incidence of PLA2R-positive de novo MN than previously reported. No significant histologic differences were identified in the initial biopsies from the two groups, except mean IgG intensity by IF was higher in the recurrent group, suggesting a higher load of immune complex deposits at diagnosis in this group. The findings do not provide support for a specific association between AMR and de novo MN, but whether there is a possible link between both forms of post-transplant MN and AMR remains an unanswered question.

Accuracy of GynTect® Methylation Markers to Detect Recurrent Disease in Patients Treated for CIN3: A Proof-of-Concept Case-Control Study.

Post-treatment follow-up in women with CIN3 is mandatory due to relapse in up to 15% of patients within 2 years. Standard follow-up care based on hrHPV-DNA/cytology co-testing has high sensitivity but limited specificity. The aim of our proof-of-concept case-control study was to evaluate the performance of the methylation test GynTect® for the detection of recurrent CIN2/3 during follow-up. Residual clinical material from a recent, prospective, multicenter, observational study was available for further analysis. We studied a sample of 17 cases with recurrent CIN2/3 diagnosed within 24 months of follow-up and 31 controls without recurrence. DNA from cervical scrapes at baseline (immediately before CIN3 surgery) and up to three follow-up visits were analyzed for hrHPV and GynTect® methylation status. Cytology data were available from the previous study. Overall, 12 cases and 21 controls were GynTect-positive at baseline. In these subgroups, single test sensitivity at first follow-up was 67% (95% CI 39-87%) for GynTect® compared to 83% (95% CI 55-96%) for hrHPV (p = 0.50). Single test specificity was significantly higher for GynTect® (90%, 95% CI 71-98% vs. 62%, 95% CI 40-80%) (p = 0.03). In a co-testing setting, both hrHPV/cytology and GynTect®/cytology detected all recurrences. Specificity for GynTect®/cytology was higher than for hrHPV/cytology, but this difference was not statistically significant. In conclusion, for initially GynTect-positive patients, both hrHPV and GynTect® tests detected recurrent disease with similar sensitivity, but the GynTect® assay has a higher specificity. Incident hrHPV infection and/or persisting multifocal hrHPV infections without clinical disease are most likely responsible for the poorer specificity of the hrHPV test. A future prospective validation study will have to show whether GynTect®/cytology co-testing can outperform hrHPV/cytology co-testing in post-treatment surveillance.

Age and Menopausal Status in Idiopathic Subglottic Stenosis.

To evaluate the impact of age on disease recurrence in idiopathic subglottic stenosis (iSGS) patients. This was a retrospective chart review of iSGS patients treated with laser wedge excision. Patients did not have prior surgery. Survival rates free of recurrence were estimated using the Kaplan-Meier methods, and associations were evaluated using Cox Proportional Hazards models. Eighty-five female patients were included in the study. Most patients (68%) were postmenopausal, had first period at or before 13 years of age, had at least one full-term pregnancy (82%), were not undergoing hormone replacement therapy (93%), were not using hormonal birth control (88%), and were either partially or completely compliant with triple therapy regime (80%). There was a statistically significant average reduction in risk of recurrence of 5% for every additional year of age (p < 0.0001). When compared to patients older than 65 years of age, patients less than 35 were nearly 10 times more likely to recur (p = 0.002), and patients 55-65 and 45-55 years of age were 8 and 5 times more likely to recur, respectively (p = 0.003 and 0.009). Additionally, females on birth control showed decreased risk of recurrence of 74% compared with their counterparts (p = 0.04). This is the first study to demonstrate an inverse relationship between age and disease recurrence in patients with iSGS following surgery. Using age as a surrogate for menopausal status, these results suggest that increased age and/or birth control provide a protective effect through decreased recurrence rates, possibly mediated by decreased estrogen levels. 4 Laryngoscope, 2024.

Predicting disease recurrence in patients with endometriosis: an observational study

BackgroundDespite surgical and pharmacological interventions, endometriosis can recur. Reliable information regarding risk of recurrence following a first diagnosis is scant. The aim of this study was to examine clinical and survey data in the setting of disease recurrence to identify predictors of risk of endometriosis recurrence.MethodsThis observational study reviewed data from 794 patients having surgery for pelvic pain or endometriosis. Patients were stratified into two analytic groups based on self-reported or surgically confirmed recurrent endometriosis. Statistical analyses included univariate, followed by multivariate logistic regression to identify risk factors of recurrence, with least absolute shrinkage and selection operator (Lasso) regularisation. Risk-calibrated Supersparse Linear Integer Models (RiskSLIM) and survival analyses (with Lasso) were undertaken to identify predictive features of recurrence.ResultsSeveral significant features were repeatedly identified in association with recurrence, including adhesions, high rASRM score, deep disease, bowel lesions, adenomyosis, emergency room attendance for pelvic pain, younger age at menarche, higher gravidity, high blood pressure and older age. In the surgically confirmed group, with a score of 5, the RiskSLIM method was able to predict the risk of recurrence (compared to a single diagnosis) at 95.3% and included adenomyosis and adhesions in the model. Survival analysis further highlighted bowel lesions, adhesions and adenomyosis.ConclusionsFollowing an initial diagnosis of endometriosis, clinical decision-making regarding disease management should take into consideration the presence of bowel lesions, adhesions and adenomyosis, which increase the risk of endometriosis recurrence.

Long-term functional, anatomical outcome, and qualitative analysis by OCTA, as a predictor of disease recurrences in patients with choroidal neovascularization secondary to angioid streaks

BackgroundTo report the risk of exudation recurrence and long-term outcomes in patients with choroidal neovascularization secondary to angioid streaks, according to its morphology and characteristics by optical coherence tomography angiography.MethodsRetrospective analysis of electronic medical records from three hospitals. We enrolled patients with a clinical diagnosis of angioid streaks choroidal neovascularization that had a minimum follow-up of 12 months. From each record, we extracted general demographic data, best corrected visual acuity (baseline, before and after each disease recurrence and last on file), type of treatment, time between last intravitreal injection and disease recurrence, and classification of the neovascular lesion morphology by optical coherence tomography, and optical coherence tomography angiography. Patients with myopic choroidal neovascularization were used as controls. Interobserver agreement was assessed with a Cohen-Kappa test. The Odds ratio was calculated with a chi2 test for significance. Visual acuity change through time was evaluated with an ANOVA for repeated measurements with an alpha value of 0.05 for statistical significance.ResultsWe enrolled 30 patients in the study group and 14 in the control group. In the study group, the baseline and final BCVA were 0.861 ± 0.59 and 1.095 ± 0.61 logMAR (p = 0.1) respectively. Control group: 1.045 ± 0.57 and 0.617 ± 0.53 logMAR (p < 0.05). In the study group, the predominant CNV type by OCTA was mixed (37%), and interlacing (57%) in the control group. Mixed and cog-wheel patterns at baseline had increased Odds for recurrence in the study group (p = 0.09). Patients in the study group required more intravitreal injections on each recurrence episode to achieve disease control (3.5 ± 1.5 vs.1.4 ± 0.2, p < 0.01).ConclusionsThe benefits of anti-VEGF treatment are lost over time in patients with angioid streaks and CNV. Lesion characteristics by optical coherence tomography angiography could help physicians predict the risk of recurrence.Trial registrationRetrospective registered, and IRB approved.

No clinical benefit from sequential combination of mitomycin C plus bacillus Calmette-Guérin (BCG) than BCG alone in the adjuvant treatment of high risk non muscle invasive bladder cancer: result of a planned interim analysis of a prospective randomized trial.

The aim of this study was to evaluate whether the sequential use of Mitomycin C (MMC) and Bacillus Calmette-Guérin (BCG) is superior to BCG alone in reducing the risk of disease recurrence in patients with non-muscle invasive bladder cancer (NMIBC) with high risk of progression. Prospective randomized trial was conducted from March 2021 to March 2023 and included 72 patients with high risk NMIBC. Trial registration number: NCT03790384; EUDRACT Number: 2017-004540-37. Thirty-one patients underwent to BCG alone and forty-one to MMC plus BCG during the induction course. The BCG schedule comprised six weekly instillation of 81 mg Connaught strain BCG as the induction course, followed by a further three-monthly instillation at three, six and twelve months, as the maintenance course. Forty mg of MMC were administered the day prior to each weekly BCG instillation in BCG plus MMC arm. A planned interim analysis was carried out in June 2023, at the end of the 12mo follow-up period. Six out of thirteen 6/31(19.3%) and 10/41 (24.4%) patients experienced recurrence in BCG and BCG plus MMC group (P=0.611), respectively. BCG plus MMC did not improve Disease Free Interval (HR: 1.23 95% CI:0.46-3.50; P=0.640). Patients receiving sequential treatment experienced similar AEs (P>0.05) and more urinary symptoms (P<0.05). This interim pre-planned analysis suggested absence of clinical advantages in terms of disease recurrence rate when MMC is administered one day prior to BCG during induction course.

Herpes Zoster Ophthalmicus: Presentation, Complications, Treatment, and Prevention.

Herpes zoster (HZ) is caused by reactivation of latent infection of varicella zoster virus (VZV) in sensory (cranial, dorsal root) ganglia. Major risk factors for HZ are increasing age and immunosuppression. HZ ophthalmicus (HZO) is a subset of HZ with involvement of the ophthalmic division of the fifth cranial trigeminal nerve. Approximately 4-20% of patients with HZ develop HZO. Approximately 50% of patients with HZO develop ocular disease, among whom up to 25% develop chronic or recurrent disease. Common manifestations of ocular disease include conjunctivitis, keratitis, and uveitis, whereas optic neuropathy and retinitis are uncommon. Due to the potential for vision impairment, ocular involvement requires urgent ophthalmic consultation. Early recognition and timely treatment with antivirals may prevent ocular complications. HZO is preventable by vaccination against HZ. Vaccine efficacy/effectiveness studies have been largely conducted for HZ with few studies assessing HZO. Both the recombinant adjuvanted vaccine (RZV) and live-attenuated vaccine (ZVL) significantly reduce the incidence of HZ and HZO in older adults. RZV is more effective than ZVL. Data on the effectiveness of vaccines for prevention of recurrent disease in patients with HZO are limited; however, vaccination is recommended. Despite recommendations to vaccinate individuals likely to benefit from an HZ vaccine, coverage for adults remains suboptimal. Barriers to vaccination include patient beliefs about HZ or HZ vaccines, and factors related to healthcare providers. In particular, the lack of a recommendation from their primary care physician is often cited by patients as a reason for remaining unvaccinated. By encouraging vaccination against HZ, physicians not only prevent HZ and HZO but also potential vision loss due to HZO.Graphical abstract available for this article.

Association between circulating tumor DNA (ctDNA) and recurrence-free survival (RFS) in patients (pts) with resected stage III melanoma: An exploratory analysis of SWOG S1404.

9564 Background: Our exploratory study aimed to understand the association between the presence of ctDNA after definitive surgical resection and RFS in pts with stage III melanoma treated with adjuvant immunotherapy. Methods: This study included 92 pts with resected stage III melanoma enrolled in a phase 3 trial (NCT02506153) that evaluated the efficacy of adjuvant pembrolizumab compared to interferon alfa-2b or ipilimumab in pts with stage IIIA(N2a)-IV resected melanoma. Personalized, tumor-informed ctDNA assays (Signatera) were run on banked plasma samples (median: 3.8 mL) collected at up to 5 time points after resection: pre-adjuvant treatment (pre-Tx), 1, 3, 6, or 12 months after Tx initiation and at recurrence. RFS was measured from randomization (pre-Tx) to first recurrence or death. A case-control design was used: 50% with recurrence within 2 yrs of randomization and 50% alive without recurrence for &gt; 2 yrs. Conditional logistic regression compared the presence of ctDNA at pre-Tx between case-control groups. Results: Of the 92 pts, samples from 10 did not pass quality control. This study analyzed a total of 245 plasma samples from 82 pts. No significant differences in demographics, including stage, number of + lymph nodes, and BRAF status, existed between pts who were ctDNA+ or ctDNA- pre-Tx. 7 of 10 pts (70.0%) who were ctDNA+ pre-Tx had disease recurrence within 2 yrs compared to 33 of 72 pts (45.8%) who were ctDNA- (p = 0.19). 2-yr RFS was 30% in pts who were ctDNA+ pre-Tx and 54% in pts who were ctDNA- (HR 1.75; 95% CI: 0.78, 3.94; p = 0.18). Of the 7 pts who were ctDNA+ pre-Tx and had disease recurrence within 2 yrs, 5 were ctDNA+ at all time points assessed. The other 2 pts transiently cleared ctDNA during Tx, turning back ctDNA+ prior to recurrence. Of the 3 pts who were ctDNA+ pre-Tx and did not recur within 2 yrs, 2 cleared ctDNA during immunotherapy and remained ctDNA- at later time points. All 39 pts who were ctDNA- pre-Tx and did not recur within 2 yrs remained ctDNA- at later time points. Among 29 pts having ctDNA timepoints available for analysis near the time of recurrence (end-of-Tx or on-progression timepoints), 22 (75.9%) were ctDNA+. Conclusions: In this study, pre-Tx incidence of ctDNA+ after surgical resection was low, potentially related to limited plasma yield. However, the ctDNA positivity rate increased in subsequent serial testing. ctDNA might help identify early disease recurrence in patients with melanoma in the adjuvant setting, but further studies of larger cohorts accounting for treatment effect with more uniform pre-analytic collection are needed.

Preliminary results correlating post-operative ctDNA status with disease-free survival in patients with stage II (high risk)/III colorectal cancer in the BNT000-001 epidemiology study.

3526 Background: Despite standard-of-care surgical resection and adjuvant chemotherapy (ACT), disease recurrence in patients (pts) with stage II or III colorectal cancer (CRC) remains high. Circulating tumor DNA (ctDNA) analysis post-surgery with curative intent may help to identify pts with minimal residual disease at risk for recurrence. We report preliminary results of the BNT000-001 study exploring the prevalence and prognostic value of ctDNA positivity post-surgery in pts with stage II (high-risk) / III CRC. Methods: The BNT000-001 (NCT04813627) epidemiological study is enrolling pts in US, Germany (including screening through the Colopredict registry study), Spain, and Belgium with resected high-risk (per NCCN guidelines) stage II / III CRC for longitudinal follow up of their ctDNA status post-surgery and ACT. The primary objective of the study is to estimate the prevalence of ctDNA positivity after surgery. Other objectives include evaluation of the prognostic value of ctDNA and identification of ctDNA positive pts who might be candidates for the interventional clinical trial BNT122-01 (NCT04486378). Disease-free survival (DFS) was measured from the post-surgery visit to disease recurrence/death and analyzed for all eligible pts who remain on study. ctDNA was analyzed using the laboratory developed AVENIO Oncology Assays (AOA) Surveillance test and reported as detected (“positive”), not detected (“negative”), or no result (“non-evaluable”). Results: 1094 pts have been screened, of which 874 pts were analyzed for post-surgery ctDNA status (data cutoff 15 Dec 2023). 142 pts were non-evaluable, resulting in 732 pts with defined ctDNA status. Prevalence of post-operative ctDNA positivity was 12.3% (90*/732). 87.7% (642/732) of pts were ctDNA negative. 826 pts were followed for the prognostic value of post-surgery ctDNA-positivity, excluding 48 ctDNA positive pts who transferred to the BNT122-01 treatment study. At a median follow-up time of 25.9 months, the median DFS of ctDNA positive pts was 12.16 months vs. median DFS not reached for ctDNA negative pts. The 12-month DFS rate was 55% for ctDNA positive vs. 92% for ctDNA negative pts. Of note, our analyses support the identification of ctDNA negative T4N2 pts as a high-risk group for recurrence. Post-surgery ctDNA positivity was associated with significantly increased risk for disease recurrence or death, with a hazard ratio of 10.2. Conclusions: This study supports existing evidence of the prognostic value of post-operative ctDNA in CRC pts. In ctDNA positive pts, the 12-month DFS rate was almost halved (55% vs. 92% in ctDNA negative). Clinical trial information: NCT04813627 . [Table: see text]

Long-term risk of delayed postoperative Crohn's disease recurrence in patients with no or mild endoscopic recurrence at first assessment.

Early endoscopic evaluation is recommended for assessment of postoperative recurrence (POR) of Crohn's disease (CD) but no further monitoring recommendations are available. To evaluate the long-term outcome of patients without endoscopic POR at first endoscopic assessment. Retrospective four-centre study including consecutive CD patients with ileocolonic resection (ICR) without endoscopic POR (Rutgeerts score i0-i1) at first endoscopic assessment performed within 18 months from ICR. All patients had a clinical follow-up ≥24 months and at least one further endoscopic assessment. Main outcomes were endoscopic, clinical and surgical POR, need for rescue therapy and "delayed POR" (any need for rescue therapy or clinical or surgical POR) during follow-up. Overall, 183 patients were included (79% with risk factors for POR, 44% without postoperative prophylaxis). Endoscopic POR was observed in 42% of patients. Clinical POR-free survival was 89.4% and 81.5% at 3 and 5 years, and delayed POR-free survival was 76.9% and 63.4% at 5 and 10 years, respectively. In multivariate analysis, postoperative prophylaxis (HR .55; 95% CI .325-.942) and active smoking (HR 1.72; 95%CI 1.003-2.962) were independent risk factors for clinical POR, whereas presence of mild endoscopic lesions at index ileocolonoscopy (i1) was the only risk factor for delayed POR (HR 1.824; 95% CI 1.108-3.002). Long-term risk of POR among patients with no or mild endoscopic lesions at first ileocolonoscopy after surgery is steadily low, being higher among smokers, in the absence of postoperative prophylaxis and when mild endoscopic lesions are observed in the first endoscopic assessment.

Late-onset lymphopenia during radiation is associated with an increased risk of tumor recurrence in newly diagnosed pediatric medulloblastoma.

Recent data found a correlation between lymphopenia occurring early during craniospinal radiation therapy (RT) and risk of disease recurrence in newly diagnosed childhood medulloblastoma. However, the population included patients who received chemotherapy prior to or during RT. Here, we investigate the effect of lymphopenia during RT in patients with newly diagnosed pediatric medulloblastoma who were chemotherapy-naïve. We analyzed 79 patients with newly diagnosed medulloblastoma (ages 2-21years) treated between 1997 and 2013 with craniospinal RT. Log-rank tests were used to determine survival differences, and Cox proportional hazards regression was used to assess associations between patient characteristics and lymphopenia with disease recurrence risk. Eighty-three percent of patients (62/75) had grade ≥3 lymphopenia by RT Week 3, with 95% developing grade ≥3 lymphopenia at some point during therapy. There was no difference in incidence of lymphopenia between those who received proton beam RT (93%) versus photon (97%). Twenty-four of 79 (30%) patients developed disease recurrence at an average 27.0months after diagnosis. There was higher risk of disease recurrence in patients with grade ≥3 lymphopenia during RT Week 4 (log-rank p=.016; Cox p=.03) and Week 5 (log-rank p=.024; Cox p=.032); after adjusting for clinical risk group, only grade ≥3 lymphopenia at Week 4 remained prognostic (Cox p=.04). No correlation was found between risk of tumor recurrence and early lymphopenia (RT Weeks 0-3) or absolute lymphocyte count (ALC) below the median at any time during RT. Lymphopenia during RT Weeks 4 and 5 correlates with increased risk of tumor recurrence in pediatric patients with newly diagnosed medulloblastoma.

Longitudinal Tumor-informed Circulating Tumor DNA Status Predicts Disease Upstaging and Poor Prognosis for Patients Undergoing Radical Cystectomy

Background and objectiveDecision-making on the use of neoadjuvant and adjuvant treatment for patients with bladder cancer undergoing radical cystectomy (RC) currently depends on assessment of clinical and pathological features, which lack sensitivity. Circulating tumor DNA (ctDNA) has emerged as a possible novel prognostic biomarker in the field. Our aim was to assess whether ctDNA status before RC is predictive of pathological and oncological outcomes. We also evaluated the dynamic changes in ctDNA status after RC in relation to recurrence-free survival (RFS). MethodsWe analyzed data for patients who underwent RC during 2021–2023 for whom prospective tumor-informed ctDNA analyses were conducted before and after RC. RFS was evaluated using the Kaplan-Meier method. Predictors for disease recurrence were assessed using Cox proportional-hazards models. Pathological outcomes associated with detectable ctDNA before RC were assessed in univariable and multivariable regression analyses. Key findings and limitationsWe included 112 patients in the analysis. Median follow-up was 8 mo (interquartile range 4–13). ctDNA was detected before RC in 59 patients (53%) and was associated with poor RFS (log-rank p < 0.0001). Detectable ctDNA before RC was associated with poor outcomes regardless of clinical stage (<cT2 vs ≥cT2) and receipt of neoadjuvant therapy. Multivariable analyses revealed that detectable ctDNA before RC was associated with a higher risk of nodal disease (odds ratio 5.4, 95% confidence interval [CI] 1.9–18.2; p = 0.003) and locally advanced disease (odds ratio 3.6, 95% CI 1.5–9; p = 0.005). Cox regression analyses showed that detectable ctDNA before RC (hazard ratio 4.5, 95% CI 1–19; p = 0.04) and detectable ctDNA at the minimal residual disease window (hazard ratio 9.9, 95% CI 2.6–37; p < 0.001) were predictive of disease recurrence. Conclusions and clinical implicationsDetectable ctDNA before definitive therapy with RC is predictive of nodal involvement, locally advanced disease, and disease recurrence in patients with bladder cancer. ctDNA status holds promise for improving clinical staging and augmenting current decision-making tools. Patient summaryWe found that for patients with bladder cancer undergoing radical cystectomy, a test to show the presence of tumor DNA in blood before surgery was able to predict the risk of disease relapse and adverse pathology. Use of this assay could help in decision-making by clinicians and patients for optimal personalized treatment of this disease.

Predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa squamous cell lung cancer: A retrospective analysis.

Lung cancer (LC) is a global medical, social and economic problem and is one of the most common cancers and the leading cause of mortality from malignant neoplasms. LC is characterized by an aggressive course, and in the presence of disease recurrence risk factors, patients, even at an early stage, may be indicated for adjuvant therapy to improve survival. However, combined treatment does not always guarantee a favorable prognosis. In this regard, establishing predictors of LC recurrence is highly important both for determining the optimal treatment plan for the patients and for evaluating its effectiveness. To establish predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa lung squamous cell carcinoma (LSCC). A retrospective case-control cohort study included 69 patients with LSCC who underwent radical surgery at the Orenburg Regional Clinical Oncology Center from 2009 to 2018. Postoperatively, all patients received adjuvant chemotherapy. Histological samples of the resected lung were stained with Mayer's hematoxylin and eosin and examined under a light microscope. Univariate and multivariate analyses were used to identify predictors associated with the risk of disease recurrence. Receiver operating characteristic curves were constructed to discriminate between patients with a high risk of disease recurrence and those with a low risk of disease recurrence. Survival was analyzed using the Kaplan-Meier method. The log-rank test was used to compare survival curves between patient subgroups. Differences were considered to be significant at P < 0.05. The following predictors of a high risk of disease recurrence in patients with stage IIb-IIa LSCC were established: a low degree of tumor differentiation [odds ratio (OR) = 7.94, 95%CI = 1.08-135.81, P = 0.049]; metastases in regional lymph nodes (OR = 5.67, 95%CI = 1.09-36.54, P = 0.048); the presence of loose, fine-fiber connective tissue in the tumor stroma (OR = 21.70, 95%CI = 4.27-110.38, P = 0.0002); and fragmentation of the tumor solid component (OR = 2.53, 95%CI = 1.01-12.23, P = 0.049). The area under the curve of the predictive model was 0.846 (95%CI = 0.73-0.96, P < 0.0001). The sensitivity, accuracy and specificity of the method were 91.8%, 86.9% and 75.0%, respectively. In the group of patients with a low risk of LSCC recurrence, the 1-, 2- and 5-year disease-free survival (DFS) rates were 84.2%, 84.2% and 75.8%, respectively, while in the group with a high risk of LSCC recurrence the DFS rates were 71.7%, 40.1% and 8.2%, respectively (P < 0.00001). Accordingly, in the first group of patients, the 1-, 2- and 5-year overall survival (OS) rates were 94.7%, 82.5% and 82.5%, respectively, while in the second group of patients, the OS rates were 89.8%, 80.1% and 10.3%, respectively (P < 0.00001). The developed method allows us to identify a group of patients at high risk of disease recurrence and to adjust to ongoing treatment.