Initiation Of Adjuvant Therapy Research Articles

Real-world use and outcomes of targeted therapy and immunotherapy for adjuvant treatment of BRAF-mutated melanoma patients in the United States.

Using a customized, harmonized US electronic health record database, real-world prescription patterns of first-line adjuvant immunotherapy and targeted therapy were retrospectively assessed for BRAFV600-mutated melanoma. Adults with BRAFV600 mutation-positive stage IIIA-D cutaneous melanoma who received first-line adjuvant immunotherapy (nivolumab or pembrolizumab) or targeted therapy (dabrafenib plus trametinib) between 1 January 2014 and 30 August 2020 in the NOBLE database were included. Patients were followed from first-line adjuvant therapy initiation for at least 6 months, until death, progression, follow-up loss, or data cutoff. Primary endpoints were proportion of patients receiving either therapy in first-line and second-line, treatment switching, treatment timing, and status at the end of first-line therapy. Secondary endpoints included discontinuation rates, recurrence-free survival (RFS), and overall survival (OS). Of 318 patients evaluated, 67.6% received nivolumab, 14.2% pembrolizumab, and 18.2% targeted therapy as first-line adjuvant therapy. Median treatment duration was longest for nivolumab (292 days) and shortest for targeted therapy (115 days). Reason for discontinuation was recorded for 195 of 274 patients who discontinued first-line therapy; most common reasons were treatment completion and treatment-related toxicity [87/158 (55.0%) and 29/158 (18.4%), respectively, in immunotherapy-treated patients; 9/37 (24.3%) and 21/37 (56.8%) in targeted therapy-treated patients]. Median RFS and OS for targeted therapy and nivolumab were not reached and were 34.6 and 38.1 months, respectively, for pembrolizumab. These results inform on prescription preferences and clinical outcomes for BRAFV600-mutated melanoma patients in the first-line adjuvant setting.

Evaluation of long-term outcome following therapeutic mammaplasty: the effect of wound complication on initiation of adjuvant therapy and subsequent oncological outcome.

Therapeutic mammaplasty (TM) facilitates large tumour resection while maintaining optimal aesthetic outcome. It carries higher wound complication risks, which may delay adjuvant therapy initiation. Whether this delay affects oncological outcome requires evaluation. Data were collected for consecutive patients receiving TM at the Leeds breast unit (2009-2017). A prospectively maintained database was used to determine tumour characteristics, wound complication rates, receipt of adjuvant therapy and breast cancer recurrence or death. In total 112 patients (median age of 54 years) underwent 114 TM procedures. The most common histological subtypes were invasive ductal carcinoma (61.4%), invasive lobular carcinoma (13.2%) and ductal carcinoma in situ (13.2%). Of the patients, 88.2% had oestrogen receptor-positive cancer and 14% had human epidermal growth factor receptor-positive cancer; 26.3% had multifocal cancer. The median tumour size was 30mm. The median Nottingham Prognostic Index was 4.2. The local recurrence rate was 3.5% (median follow-up of 8.6 years). The 5- and 10-year disease-free survival (DFS) was 88.5% and 83.5%, and the equivalent overall survival (OS) rates were 94% and 83.5%. Wound complication rate was 23.6% (n=27), the commonest being wound infection (11.4%; n=13) and T-junction wound breakdown (10.5%; n=12). The median time to adjuvant therapy was 72 days (interquartile range [IQR] 56-90) for patients with wound complications, and 51 days (IQR 42-58) for those without. However, this delay did not affect DFS or OS (log-rank test; p=0.58 and p=0.94, respectively). This was confirmed on Cox regression analysis. Our study finding demonstrates that although wound complications after TM leads to a modest delay to adjuvant therapy, the long-term oncological outcomes were comparable with those in patients without wound complications.

Sex-Specific Survival and Treatment Delay in Oropharyngeal Squamous Cell Carcinoma.

As the majority of oropharyngeal squamous cell carcinoma (OPSCC) is diagnosed in males, outcomes among females are not well-characterized. We identify sex-specific factors in OPSCC to refine female prognostication. Retrospective cohort. National Cancer Database (NCDB). OPSCC cases from the 2004 to 2019 NCDB were identified. Sociodemographic, clinical, and treatment characteristics (including timing between diagnosis and treatment administration) were compared between sexes. Multivariable Cox proportional hazard regression models were constructed to characterize survival in overall and female-only cohorts. Similar multivariable binomial logistic regression and survival models were constructed to assess odds of treatment delays and their effects on survival, respectively. A total of 192,973 OPSCC patients were identified; 36,695 (19%) were female. Females had more human papillomavirus (HPV) negative, lower clinical T and N stage, and higher comorbidity disease. Females experienced lower survival in HPV negative (hazard ratio, HR = 1.11, P < .001) but not HPV-positive disease. Females were more likely to have any treatment initiated over the median of 28 days (odds ratio, OR = 1.04, P = .014) or delays in adjuvant radiotherapy initiation over 6 weeks (OR = 1.11, P = .032). Treatment delay over 60 days (HR = 1.17, P = .016) and delay in adjuvant therapy initiation (HR = 1.24, P = .02) were associated with worse survival among females. In one of the largest analyses of OPSCC, females had poorer survival than males, specifically in HPV-negative disease, despite presentation with less advanced disease. Notably, delays in any treatment initiation and adjuvant radiotherapy initiation were more likely in HPV-negative women and associated with worse survival, highlighting potential systemic weaknesses contributing to poor prognosis among females.

BREAST CANCER ASSISTANCE JOURNEY FROM THE PERSPECTIVE OF THE PUBLIC HEALTHCARE SERVICE OF RIO GRANDE DO SUL

Objective: This study aims to characterize the breast cancer (BC) patient journey in Rio Grande do Sul (RS), Brazil, through the perspectives of the High Complexity Oncology Assistance Centers (CACONs) and High Complexity Oncology Assistance Units (UNACONs). Methods: Conducted between March and May 2023 across 17 RS Oncology public healthcare services, the cross-sectional study utilized a 54-question questionnaire administered to healthcare professionals. The survey covered various aspects, including diagnosis, treatment, funding, and multidisciplinary teamwork. Results: Descriptive analysis revealed that BC patients undergo screening tests upon treatment entry (88.2%), with immunohistochemistry commonly performed externally (64.7%) and PCR often requested (82.4%) for adjuvant therapy initiation, taking an average of 90 to 250 days for all procedures. Patients encounter challenges such as lengthy hospital stays, extensive travel to treatment centers, treatment side effects, and high transportation expenses, often leading to treatment discontinuation. The most time-consuming stage is treatment, with subcutaneous infusion proving more time-efficient than intravenous administration. Physical limitations, mobility issues, late diagnosis (90-day average), and limited access to care significantly impact patients' quality of life. Healthcare teams face difficulties with outdated guidelines, lack of intravenous treatment facilities, and extended administration durations. Institutions confront barriers like drug shortages, guideline disparities, and logistical challenges. Conclusion: The study concludes by emphasizing the identified hurdles in BC patients' public healthcare journey, underscoring the need to address delays in screening, resource constraints, and disparities in access to care based on geographical, socioeconomic, and racial/ethnic factors to enhance overall quality of care and equity within the system.

Comparing oncologic and surgical outcomes of robotic and laparoscopic pancreatoduodenectomy in patients with pancreatic cancer: a propensity-matched analysis.

Minimally invasive Pancreatoduodenectomy (MIPD), or the Whipple procedure, is increasingly utilized. No study has compared laparoscopic (LPD) and robotic (RPD) approaches, and the impact of the learning curve on oncologic, technical, and post-operative outcomes remains relatively understudied. The National Cancer Database was queried for patients undergoing LPD or RPD from 2010 to 2020 with a diagnosis of pancreatic cancer. Outcomes were compared between approaches using propensity-score matching (PSM); the impact of annual center-level volume of MIPD was also assessed by dividing volume into quartiles. A total of 3,342 patients were included. Most (n = 2,716, 81.3%) underwent LPD versus RPD (n = 626, 18.7%). There was a high rate (20.2%, n = 719) of positive margins. Mean length-of-stay (LOS) was 10.4 ± 8.9days. Thirty-day mortality was 2.8% (n = 92) and ninety-day mortality was 5.7% (n = 189). PSM matched 625 pairs of patients receiving LPD or RPD. After PSM, there was no differences between groups based on age, sex, race, CCI, T-stage, neoadjuvant chemo/radiotherapy, or type of PD. After PSM, there was a higher rate of conversion to open (HR = 0.68, 95%CI = 0.50-0.92)., but there was no difference in LOS (HR = 1.00, 95%CI = 0.92-1.11), 30-day readmission (HR = 1.08, 95% CI = 0.68-1.71), 30-day (HR = 0.78, 95% CI = 0.39-1.56) or 90-day mortality (HR = 0.70, 95% CI = 0.42-1.16), ability to receive adjuvant therapy (HR = 1.15, 95% CI = 0.92-1.44), nodal harvest (HR = 1.01, 95%CI = 0.94-1.09) or positive margins (HR = 1.19, 95% CI = 0.89-1.59). Centers in lower quartiles of annual volume of MIPD demonstrated reduced nodal harvest (p = 0.005) and a higher rate of conversion to open (p = 0.038). Higher-volume centers had a shorter LOS (p = 0.012), higher rate of initiation of adjuvant therapy (p = 0.042), and, most strikingly, a reduction in 90-day mortality (p = 0.033). LPD and RPD have similar surgical and oncologic outcomes, with a lower rate of conversion to open in the robotic cohort. The robotic technique does not appear to eliminate the "learning curve", with higher volume centers demonstrating improved outcomes, especially seen at minimum annual volume of 5 cases.

Abstract B017: Disease free survival as a predictor of overall survival in patients with high-risk endometrial cancer receiving adjuvant chemotherapy

Abstract Introduction: Disease-free survival (DFS) is often evaluated as a primary endpoint in early settings for several cancers, including endometrial cancer (EC). However, the role of DFS as a potential predictor of overall survival (OS) in EC is unknown. Elucidating the association between DFS and OS in EC is critical for contextualizing findings from trials where DFS is a primary endpoint, such as KEYNOTE-B21, which assesses the effect of treatment with pembrolizumab + adjuvant chemotherapy (CTX) vs. adjuvant CTX, with or without radiotherapy in patients with EC at high risk of recurrence. This real-world study assessed the association between DFS and OS and the impact of recurrence on OS in elderly patients with EC at high risk of recurrence receiving adjuvant CTX. Methods: SEER-Medicare data (2007–2019) were used to identify patients with EC at high risk of recurrence who received adjuvant CTX with or without radiotherapy. Patients were defined as high risk of recurrence if they had either Stage I or II EC with non-endometroid histology or Stage III or IVA EC with any histology. An EC recurrence was defined as having a diagnosis with a distinct secondary cancer &amp;gt;90 days after end of adjuvant CTX or receipt of additional cancer treatment &amp;gt;90 days after end of adjuvant CTX. Kaplan-Meier (KM) analyses were used to estimate OS (time from initiation of adjuvant therapy [index date] to death) and DFS (time from index date to earliest of recurrence or death). The correlation between DFS and OS was assessed using Kendall’s τ rank correlation. Landmark analyses were used to compare OS between patients with vs. without a recurrence at 1-, 3-, and 5-years post the index date; hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using adjusted Cox models. KM analyses were used to estimate OS from a recurrence (index date) for recurrent patients and from an imputed index date (using frequency matching) for non-recurrent patients. Results: Of 794 eligible patients, 253 (31.9%) experienced a recurrence over a median follow up of 3.6 years. Median age at diagnosis was 71.9 years, 69.8% had stage I/II disease, and 86.6% had non-endometrioid carcinoma. Median OS was not reached (5-year OS: 72.5%) and median DFS was 7.9 years (5-year DFS: 58.7%). A significant positive correlation between DFS and OS was observed (Kendall’s τ =0.83; 95% CI: 0.79–0.86; p&amp;lt;0.001). Patients with a recurrence had significantly higher risk of death than those without, at landmark points 1- (HR: 4.4; 95% CI: 2.8–7.0; p&amp;lt;.001), 3- (HR: 5.2; 95% CI: 3.1–8.7; p&amp;lt;.001), and 5-years (HR: 5.1; 95% CI: 2.2–11.7; p&amp;lt;.001). Patients with a recurrence had significantly shorter median OS than those without (median OS: 1.4 years vs. not reached; p&amp;lt;.001). Conclusions: In elderly patients with EC at high risk of recurrence who received adjuvant CTX, DFS was strongly correlated with OS and having a recurrence was associated with significantly higher risk of death. Our findings suggest that DFS is a strong predictor of OS in this population and may be a useful surrogate endpoint. Citation Format: Kalé Kponee-Shovein, Vimalanand S. Prabhu, Yan Song, Lei Chen, Mu Cheng, Yeran Li, Yezhou Sun, Annalise Hilts, Qi Hua, Jasmine Lichfield, Linda Duska. Disease free survival as a predictor of overall survival in patients with high-risk endometrial cancer receiving adjuvant chemotherapy [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B017.

Airway protection and outcomes after staged versus concurrent bilateral neck dissections with transoral base of tongue cancer resection.

To assess airway, safety, and resource utilization outcomes between transoral base of tongue (BOT) surgery with staged versus concurrent bilateral neck dissections (BND). A retrospective cohort study of patients with human papilloma virus (HPV)-related BOT cancer who underwent transoral surgery and BND from January 2015 through June 2022 was conducted. Free flap patients were excluded. Of 126 patients (46 [37%] staged and 80 [63%] concurrent BND), there were no significant differences in rates of postoperative intubation, tracheostomy, intensive care admission, operative takebacks, gastrostomy, and 30-day readmission. Total operative time (median difference 1.4 [95% CI 0.9-1.8] hours), length of stay (1.0 [1.0-1.0] day), and time between primary surgery and adjuvant therapy initiation (4.0 [0.0-8.0] days) were lower in the concurrent BND cohort. Concurrent BND alongside transoral BOT resection is safe with similar airway outcomes and lower total operative time, length of stay, and time to adjuvant therapy initiation compared to staged BND.

From molecular signatures to radiomics: tailoring neurooncological strategies through forecasting of glioma growth.

Contemporary oncological paradigms for adjuvant treatment of low- and intermediate-grade gliomas are often guided by a limited array of parameters, overlooking the dynamic nature of the disease. The authors' aim was to develop a comprehensive multivariate glioma growth model based on multicentric data, to facilitate more individualized therapeutic strategies. Random slope models with subject-specific random intercepts were fitted to a retrospective cohort of grade II and III gliomas from the database at Kepler University Hospital (n = 191) to predict future mean tumor diameters. Deep learning-based radiomics was used together with a comprehensive clinical dataset and evaluated on an external prospectively collected validation cohort from University Hospital Zurich (n = 9). Prediction quality was assessed via mean squared prediction error. A mean squared prediction error of 0.58 cm for the external validation cohort was achieved, indicating very good prognostic value. The mean ± SD time to adjuvant therapy was 28.7 ± 43.3 months and 16.1 ± 14.6 months for the training and validation cohort, respectively, with a mean of 6.2 ± 5 and 3.6 ± 0.7, respectively, for number of observations. The observed mean tumor diameter per year was 0.38 cm (95% CI 0.25-0.51) for the training cohort, and 1.02 cm (95% CI 0.78-2.82) for the validation cohort. Glioma of the superior frontal gyrus showed a higher rate of tumor growth than insular glioma. Oligodendroglioma showed less pronounced growth, anaplastic astrocytoma-unlike anaplastic oligodendroglioma-was associated with faster tumor growth. Unlike the impact of extent of resection, isocitrate dehydrogenase (IDH) had negligible influence on tumor growth. Inclusion of radiomics variables significantly enhanced the prediction performance of the random slope model used. The authors developed an advanced statistical model to predict tumor volumes both pre- and postoperatively, using comprehensive data prior to the initiation of adjuvant therapy. Using radiomics enhanced the precision of the prediction models. Whereas tumor extent of resection and topology emerged as influential factors in tumor growth, the IDH status did not. This study emphasizes the imperative of advanced computational methods in refining personalized low-grade glioma treatment, advocating a move beyond traditional paradigms.

Postoperative complications following neoadjuvant therapy and surgery in a phase 2 borderline resectable pancreatic cancer clinical trial (Alliance A021501).

664 Background: Postoperative complications in patients with borderline resectable pancreatic cancer treated with neoadjuvant therapy and pancreatectomy in the national cooperative group setting have not been previously characterized. Further, the impact of preoperative hypofractionated radiotherapy on postoperative outcomes is largely unknown. We sought to quantify perioperative morbidity among patients with pancreatic cancer who received neoadjuvant modified FOLFIRINOX chemotherapy with or without hypofractionated radiotherapy on a multicenter clinical trial. Methods: The A021501 phase 2 trial randomized patients with borderline resectable pancreatic ductal adenocarcinoma to 8 doses of mFOLFIRINOX (Arm 1) or 7 doses of mFOLFIRINOX then hypofractionated radiotherapy (Arm 2), followed by pancreatectomy (Dec 31, 2016-Jan 1, 2019). Patients underwent resection according to defined operative standards at enrolling centers without specific requirements for either surgeon or hospital volume. Surgical complications and adverse events were assessed and captured at a single time point of 90 days after surgery and compared between treatment arms. Results: Of 126 enrolled patients, 51 (40%) underwent pancreatectomy (n=32, Arm 1; n=19, Arm 2) at 28 institutions. Vascular resection was performed in 19 patients (37%). One patient in Arm 2 died within 90 days after surgery. Rates of any surgical complication were 19% (n=6) in Arm 1 and 42% (n=8) in Arm 2 (p=0.07). Median length of stay was 7 days (range 5-38 days). Five (10%) patients required reoperation within 90 days. Readmission rates were higher in Arm 2 than Arm 1 (16% vs. 42%, p=0.04) but there were no differences in rates of reoperation, pancreatic fistula or abscess requiring drainage, or wound infection between study arms. 54% of patients (n=26/48) experienced a grade 3 or higher adverse event, with no difference between treatment arms (47% versus 67%, p=0.7). Rates of initiation of adjuvant therapy did not differ between treatment arms (66% vs. 68%, p=0.4). Pancreatic fistula and abscess were associated with adjuvant therapy (p&lt;0.01). No difference in overall survival was observed based on occurrence of surgical complications (HR 1.1; 95% CI 0.5-2.6). Conclusions: In this national cooperative group study of patients with borderline resectable pancreatic cancer,postoperative complications following neoadjuvant chemotherapy, radiation, and surgical resection were consistent with rates previously reported by high-volume institutions and using large datasets. Multimodality trials of preoperative therapy for locoregionally advanced pancreatic cancer may be safely performed in the cooperative group setting. Clinical trial information: NCT02839343 .

Effect of time interval between surgery and the initiation of adjuvant therapy on the oncologic outcomes of early-stage endometrial cancer.

To identify the impact of time interval between surgery and initial adjuvant radiotherapy on oncologic outcomes in early-stage endometrial cancer. This retrospective cohort study included patients with stage I/II endometrial cancer who underwent surgical staging and adjuvant therapy at Songklanagarind Hospital from January 1, 2007, to December 31, 2017. Patients were categorized into two groups: TI <6 weeks and TI ≥6 weeks. The effects of TI and clinicopathological factors on recurrence-free survival (RFS) and overall survival (OS) were analyzed using Cox proportional-hazards regression. In total, 177 patients were enrolled, with 52% receiving adjuvant radiotherapy at <6 weeks (overall median TI 5.7 weeks). The recurrence and death rates were 13% and 10.2%, respectively. The median follow-up time was 46.6 months. The overall 3-year RFS and OS rates were 88.2% and 85.2%, respectively. The TI significantly affected the 3-year RFS (94.4% vs 81.2%; P = 0.008) and 3-year OS (95.5% vs 83.2%; P = 0.012) in patients with TI <6 and ≥6 weeks, respectively. In multivariate analysis, the depth of myometrial invasion (MI), presence of lymphovascular space invasion, and TI were independent prognostic factors for both RFS and OS. Delaying the TI (≥6 weeks) was significantly associated with a worse RFS (hazard ratio [HR] 3.70; 95% confidence interval [CI]: 1.34-10.22; P = 0.012) and an inferior OS (HR 3.80; 95% CI: 1.23-11.69; P = 0.02). A delay in the TI between surgery and the initiation of adjuvant radiotherapy of ≥6 weeks negatively affected the oncologic outcomes in early-stage endometrial cancer.

Contralateral prophylactic mastectomy: Weighing the risks of delayed chemotherapy, radiotherapy, and hormonal therapy

Many patients with unilateral breast cancer opt for contralateral prophylactic mastectomy (CPM) at the time of therapeutic mastectomy (immediate CPM) or following completion of adjuvant therapy. Studies show that immediate CPM increases the risk of surgical complications related to unilateral mastectomy (UM) alone, which may lead to delays in adjuvant therapy initiation. However, it is unclear if these complications cause clinically significant delays in initiating adjuvant chemotherapy, radiotherapy, or hormonal therapy. A retrospective chart review was conducted on patients with breast cancer who underwent immediate CPM versus UM alone at Columbia University Medical Center from January 2000 to December 2020. Patient demographic and oncologic characteristics; complications; and timing of adjuvant chemotherapy, radiotherapy, and/or hormonal therapy relative to therapeutic mastectomy were collected. In this study, 239 UM alone patients were propensity score matched to 239 immediate CPM patients. No significant difference in complication rates was found between the index and contralateral breasts in CPM patients. A similar percentage of CPM and UM patients experienced postoperative complications (19% vs. 17%, p = 0.64). No significant difference in time to adjuvant chemotherapy, radiotherapy, or hormonal therapy was found between CPM patients with complications and all CPM patients or all UM patients. There is a lack of clear guidance for clinical decision-making regarding timing of CPM relative to adjuvant therapy. Our study suggests that immediate CPM does not significantly increase the risks of postoperative complications or complication-related delays in the initiation of adjuvant chemotherapy, radiotherapy, or hormonal therapy. This information may help patients and providers to plan, select, and schedule breast cancer treatment options.

The Buccal Fat Pad as a Primary Flap for the Reconstruction of Intraoral Defect After Resection of Oral Cavity Malignant Tumors: A Retrospective Study.

Among the various local and regional flaps used for the reconstruction of intraoral defects after oral cavity cancer surgery, the pedicled buccal fat pad (BFP) flap is considered a reliable alternative. Reconstruction with a BFP flap is particularly feasible in oral cavity areas, such as the posterior maxilla, buccal mucosa, retromolar trigone, and gingivobuccal sulcus. The purpose of this study was to analyze the outcomes of pedicled BFP as a primary reconstruction flap for small to medium intraoral posterior oral cavity postresection defects operated in our institute. This study was designed as a retrospective study. Thirty-seven patients with oral cavity cancer underwent wide local excision with adequate margins, followed by reconstruction of the defect with a pedicled BFP flap. Defect size, postoperative healing of the surgical site, mouth opening at 6 months, and any associated complications were assessed. The mean age of the patients was 47.38±9.95 years with a male-to-female ratio of 3.6:1. Mean defect size at the greatest dimension was 5.01±1.39 cm. The mean preoperative mouth opening of patients was 35±6.4 mm, whereas the mean postoperative mouth opening after 6 months of follow-up was 27.8±9.2 cm. The BFP flap is a convenient, reliable, and feasible reconstruction modality after oncological resection of posterior oral cavity cancers. Harvesting a BFP flap is minimally invasive with fewer complications, shorter recovery time, no donor site morbidity, and allows early initiation of adjuvant therapy postoperatively.

Efficacy and Safety of Perampanel in Children with Drug-Resistant Focal-Onset Seizures: A Retrospective Review

Background: Epilepsy is one of the most common neurological disorders. Existing antiseizure medications (ASMs) are still unable to control seizures in one-third of these patients, making the discovery of antiseizure therapies with novel mechanisms of action a necessity. Aim of the Study: This study aimed to determine the safety and efficacy of perampanel (PER) as an adjuvant treatment for children with drug-resistant focal-onset seizures with or without focal to bilateral tonic-clonic seizures. Patients and methods: This is a single-center retrospective study of 38 epileptic pediatric patients, aged 2 to 14, at King Faisal Specialist Hospital and Research Center whose seizures were pharmaco-resistant to more than two antiseizure medications and followed for at least three months after PER adjuvant therapy initiation. Efficacy was assessed by the PER response rate at 3-, 6-, and 12-month follow-up evaluations, and side effects were also reported. Results: Multiple seizure types were reported. Myoclonic seizures were the predominant type of epilepsy in 17 children (44.7%). At 3 months, 6 months, and 12 months of follow-up, approximately 23.4%, 23.4%, and 18.4% of the patients were seizure-free at these time points, respectively. Adverse events were documented in 14 patients (35.7%) and led to the discontinuation of PER in 26.3%, 31.6%, and 36.8% of the studied group at the 3-, 6-, and 12-month follow-ups, respectively. The most common adverse events included dizziness or drowsiness, irritability, gait disturbance, and confusion; however, all were transient, and no serious adverse effects occurred. Conclusion: Our findings confirm the therapeutic efficacy of adjunctive PER in the treatment of drug-resistant epilepsy in children. As an adjunctive treatment for epilepsy, perampanel demonstrated sufficient effectiveness and tolerability.

R1 pancreatic cancer patients benefit from chemoradiation when initiation of adjuvant therapy is delayed

BackgroundAdjuvant chemotherapy (AC) following pancreaticoduodenectomy (PD) for pancreas cancer (PDAC) has been demonstrated to improve survival. However, the optimal adjuvant treatment (AT) regimen for R1-margin patients remains unclear. This retrospective study investigates the impact of AC vs. adjuvant chemoradiotherapy (ACRT) on survival (OS). Material and methodsThe NCDB was queried for patients with PDAC who underwent PD between 2010 and 2018. Patients were divided into, (A) AC<60 days, (B) ACRT<60 days, (C) AC≥60 days, and (D) ACRT≥60 days. Kaplan-Meier survival analyses and Cox multivariable regression analyses were performed. ResultsAmong 13 740 patients, median OS was 23.7 months. For R1 patients, median OS for timely AC and ACRT, and delayed AC and ACRT was 19.91, 19.19, 15.24, 18.96 months, respectively. While time of AC initiation was an insignificant factor for R0 patients (p = 0.263, CI 0.957–1.173), a survival benefit was found for R1 patients who received AC<60 vs. ≥60 days (p = 0.041, CI 1.002–1.42). Among R1 patients, administration of delayed ACRT achieves the same survival benefit of timely AC initiation (p = 0.074, CI 0.703–1.077). ConclusionThe study suggests value in ACRT for patients with R1 margins when delay of AT≥60 days cannot be avoided. Hence, ACRT may mitigate the negative impact of delayed AT initiation for R1-patients.

Quality-of-life measurement in high-risk patients with uveal melanoma receiving adjuvant sunitinib or valproic acid.

e18692 Background: Despite the successful treatment of primary uveal melanoma (UM), metastasis occurs in up to half of the patients with UM. To delay metastasis for high-risk patients with UM, adjuvant therapy with sunitinib malate or valproic acid (VPA) is used. Therefore, assessing and addressing quality of life (QOL) during adjuvant therapy is essential to mitigate interferences that may prevent these patients from adherence to the therapy protocol and impair their well-being. The objective of this study is to analyze the QOL of these patients during adjuvant therapy with sunitinib or VPA, and to explore differences by the type of adjuvant therapy, age, sex, and the duration of adjuvant therapy. Methods: We analyzed longitudinal surveys of the FACT-G completed by high-risk patients with UM who participated in the randomized phase II clinical trial cohort 1 receiving 6 months of adjuvant sunitinib or VPA and Cohort 2 receiving 12 months of adjuvant sunitinib at a single center. Data were obtained before the initiation of adjuvant therapy and at 1, 3, and 6 months in cohort 1 and at 1, 3, 6, 9, and 12 months in cohort 2. We examined whether there were associations of QOL with the type of adjuvant therapy, age category, sex, and the time of adjuvant therapy using generalized estimating equations (GEE) modeling under the autoregressive working correlation structure (AR1) indexed within subjects by time. Results: There were 720 survey responses collected from 149 UM patients. In our sample, 70.4% (Cohort 1a, n = 45 and Cohort 2, n = 60) were treated with sunitinib and 29.5% (Cohort 1b, n = 44) with VPA. There was no significant difference in the QOL between the sunitinib group 1a and the VPA group 1b (p = 0.958). There was no significant difference in the overall QOL by age range (p = 0.093). However, participants aged 18 to 44 years had significantly lower emotional well-being mean scores (15.32, 95% Cl [13.53, 17.11]) compared to participants aged 65 years and above (19.06, 95% Cl [18.27, 19.86], p &lt; 0.001) but no significant difference with participants aged 45 to 64 years (18.35, 95% Cl [17.53, 19.16], p = 0.193). There was no significant difference in the QOL by sex (p = 0.863) or trend in overall QOL means scores over time as the estimated slope of 0.02 QOL units per month was not significant (95% CI [-0.35, 0.38], p = 0.94). Conclusions: In our high-risk patients with UM, the type of adjuvant therapy, age, sex, and time of adjuvant therapy were not significantly differentiating factors for the QOL scores. Participants aged 18 to 44 years had significantly lower emotional well-being scores. We did not find enough evidence to suggest that there was a change in QOL during adjuvant therapy with sunitinib or VPA.

When to treat: A multicenter retrospective study of timing of radiation therapy in 1p19q co-deleted, IDH mutated oligodendrogliomas.

e14036 Background: Oligodendrogliomas, molecularly defined by IDH mutation and 1p19q codeletion, have a protracted natural history and are more chemoresponsive compared to astrocytomas. While the addition of chemotherapy to radiation improves survival, if chemoradiation should be initiated following diagnosis or at progression remains unknown. Given the potential for early and late radiation-related toxicity, a careful evaluation of timing of treatment is critical to optimize treatment guidelines for oligodendroglioma. We aimed to evaluate the benefit of initial adjuvant radiation therapy (RT) on survival in patients with oligodendrogliomas. Methods: We conducted a multicenter retrospective study of patients treated at the University of Washington and Stanford Medical Center with oligodendrogliomas using both 1p19q codeletion and IDH mutation to define the diagnosis, reflecting the World Health Organization 2021 diagnostic criteria. Survival probability, overall survival (OS) and time to first progression (PFS), were calculated using Kaplan-Meier method with distributions compared using log-rank test in GraphPad Prism. Propensity Score Matching was completed using XLSTAT. Results: 243 patients were identified as oligodendroglioma and 229 had treatment and survival data available with a median follow up of 5.8 years(y). Median OS was 22.5y and median PFS was 5.35y. 110 patients were treated with adjuvant radiation (aRT) within 1y of diagnosis and 119 underwent observation or chemotherapy alone (delayed RT, or dRT). PFS was comparable between aRT (7.7y) and dRT (4.6y) but OS was longer in dRT (27.8y) than aRT (13.7y) (p &lt; 0.001). Given imbalance in baseline characteristics, propensity score matching was used to adjust for high risk factors of age, grade and presence of residual disease resulting in 63 pairs. In this matched cohort, aRT prolonged PFS (aRT = 7.75y v. dRT = 4.33y, p = 0.006) however dRT still demonstrated a survival benefit (p = 0.017). 59 dRT patients were treated with RT at progression and also had longer medan OS of 22.6y compared to 13.7y in the aRT (p = &lt; 0.0001). The time to RT for this cohort ranged be 1.1-19y. Conclusions: To our knowledge this is the largest retrospective study of molecularly defined oligodendrogliomas that includes treatment information. This study confirms the protracted natural history of this disease. In our multi-institution cohort, early adjuvant radiation therapy may increase PFS but was not found to prolong OS. Prospective studies evaluating the timing of treatment in patients with oligodendroglioma are needed. [Table: see text]

Investigating the patterns of treatment failure in patients with advanced stage III and IV melanoma receiving adjuvant therapy.

e21532 Background: The landscape of treatment of patients with resectable stage III melanoma has evolved considerably given studies demonstrating survival benefit of anti-PD-1 immunotherapy and BRAF/MEK-inhibitor (BRAF/MEKi) therapy in the adjuvant setting, as well as surgical changes relating to the Multicenter Selective Lymphadenectomy Trial (MSLT)-II trial. Currently, the decision to treat with anti-PD-1 or BRAF/MEKi therapy in the adjuvant setting is dependent upon patient, provider, and institutional preferences, but no comparative analysis has been done between adjuvant therapy options. Methods: Clinical data from 141 surgically-resected staged III and oligometastatic stage IV patients receiving adjuvant anti-PD-1 (n = 66), BRAF/MEKi (n = 36), or surgery only (n = 39) between 2017 and 2021 was analyzed retrospectively. Primary endpoints were overall survival (OS) and progression free survival (PFS) between the three treatment groups. Secondary endpoints include the duration of adjuvant treatment and reasons for termination of therapy. Results: During a mean follow-up period of 17 months, 33.3% of anti-PD-1 patients and 16.7% of BRAF/MEKi patients experienced recurrence, while 41.0% of the surgery only patients experienced recurrence. In univariate Cox regression analyses of the survival data, patients who received anti-PD-1 (HR = 0.46, 95% CI: 0.25-0.87, p = 0.016) or BRAF/MEKi (HR = 0.44, 95% CI:0.21-0.90, p = 0.024) had significantly improved PFS compared to patients treated with surgery only, but the OS was not significantly different with treatment. A multivariate Cox regression model was performed, adjusting for age, sex, and melanoma disease stage. In this model, anti-PD-1 was still associated with improved PFS (HR = 0.33, p &lt; 0.001), while BRAF/MEKi also trended towards improved PFS, but was not statistically significant (HR = 0.54, p = 0.13). Other associations include males having a significantly worse PFS (HR = 2.32, p = 0.009) and OS (HR = 5.86, p = 0.02), and patients with stage IIIC or worse disease having worse PFS (HR = 4.56, p &lt; 0.001), but not significantly worse OS (HR = 4.84, p = 0.05). The average duration of adjuvant therapy was similar between both groups (250-260 days) with approximately half of the patients completing the treatment course. A larger proportion of BRAF/MEKi patients stopped treatment due to intolerable side effects compared to anti-PD-1 patients (83.3% vs. 64.0%). Conclusions: Adjuvant treatment decreases the chance of recurrence compared to surgery alone, but the benefit on overall survival is still inconclusive. Male and more advanced stage III melanoma prior to initiating adjuvant therapy are factors associated with an increased likelihood of recurrence. Although it appears that more patients terminated BRAF/MEKi therapy early due to side effects compared to anti-PD-1, additional follow-up will be needed to confirm this finding.

Prophylactic Muscle Flaps Decrease Wound Complication Rates in Patients with Oncologic Spine Disease.

Patients with oncologic spine disease face a high systemic illness burden and often require surgical intervention to alleviate pain and maintain spine stability. Wound healing complications are the most common reason for reoperation in this population and are known to impact quality of life and initiation of adjuvant therapy. Prophylactic muscle flap (MF) closure is known to reduce wound healing complications in high-risk patients; however, the efficacy in oncologic spine patients is not well established. A collaboration at our institution presented an opportunity to study the outcomes of prophylactic MF closure. The authors performed a retrospective cohort study of patients who underwent MF closure versus a cohort who underwent non-MF closure in the preceding time. Demographic and baseline health data were collected, as were postoperative wound complication data. A total of 166 patients were enrolled, including 83 patients in the MF cohort and 83 control patients. Patients in the MF group were more likely to smoke ( P = 0.005) and had a higher incidence of prior spine irradiation ( P = 0.002). Postoperatively, five patients (6%) in the MF group developed wound complications, compared with 14 patients (17%) in the control group ( P = 0.028). The most common overall complication was wound dehiscence requiring conservative therapy, which occurred in six control patients (7%) and one MF patient (1%) ( P = 0.053). Prophylactic MF closure during oncologic spine surgery significantly reduces the wound complication rate. Future studies should examine the precise patient population that stands to benefit most from this intervention. Therapeutic, III.

Pre-operative and early postoperative health-related quality of life of breast cancer woman: a Lebanese prospective study

Breast cancer (BC) is a major health concern in Lebanon, with an increasing incidence rate due to advancements in treatment modalities. Evaluating the impact of the BC and its treatment on a woman's Health-Related Quality of Life (HRQoL), and comparing these patterns before and after breast conserving surgery is important to identify areas where interventions may be needed to improve the overall well-being of women with BC. This study aimed to evaluate the HRQoL pre and post-operative breast conserving surgery and just prior to initiation of adjuvant therapy in newly diagnosed patients with BC in Lebanon, specifically focusing on changes in body image. A prospective cohort study was conducted on 120 patients in two health care facilities in Lebanon, collecting sociodemographic and clinical data, and using the EORTC QLQ-C30 and QLQ-BR23 questionnaires to evaluate HRQoL. The outcomes were measured at baseline and then one-day post-operative breast surgery. Results revealed a statistically and clinically significant decrease in body image (mean difference of 8.1 points (95% 4.3;11.1)), physical functioning (mean difference of 6.1 points (95% 3.3;8.5)), and emotional functioning (mean difference of -8.4 points (95%-12.4; -4.9) after surgery. Positive change of physical functioning score was observed among married women. Positive change of emotional functioning score was observed among patients with poor body image score and high future perspective score. Our findings provide valuable insights for clinicians and researchers on the impact of breast conserving surgery on HRQoL in Lebanese women.

Oncocytic adrenocortical neoplasm of borderline uncertain malignant potential diagnosed after robot-assisted adrenalectomy case report

BackgroundAdrenal incidentalomas are radiologically discovered tumors that represent a variety of pathologies, with the diagnosis clinched only on surgical pathology. These tumors may be clinically monitored, but triggers for surgery include size > 4 cm, concerning features on radiology, or hormonally functioning. Adrenal oncocytic neoplasms (AONs) are notably rare and typically nonfunctional tumors that are discovered as incidentalomas and exist on a spectrum of malignant potential.Case presentationWe discovered an exceptionally large (15 cm in the greatest dimension) incidentaloma in a 73-year-old man with left back pain and he was treated with robotic-assisted adrenalectomy. Surgical pathology was consistent with AON of borderline uncertain malignant potential; adjuvant mitotane and radiation were omitted based on shared decision-making.ConclusionLarge AONs are rare, usually benign tumors that can be safely treated with robotic-assisted adrenalectomy. Surgical pathology is the crux of diagnosis and post-operative management, as it informs both the initiation of adjuvant therapy and the stringency of post-operative surveillance.