bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic significance of immune-related adverse events and immunosuppression in patients with melanoma receiving adjuvant anti-PD-1 therapy.
Authors: Knight Andrew David , Karapetyan Lilit , Bruno Sabrina , Abushukair Hassan Mohammed , Bo Na , Wang Hong , Sander Cindy , Kirkwood John M. M. 
Published: June 2023

9580 Background: Treatment with anti-Programmed Death-1 (PD-1) therapy reduces the risk of recurrence for patients (PT) with resectable Stage IIB-IV melanoma (MEL). This treatment is associated with the development of immune-related adverse events (irAEs), which may necessitate use of immunosuppressive therapy and treatment discontinuation. This project investigates the impact of irAE and immunosuppressive therapy in survival outcomes of PTs with MEL. Methods: PTs with stage IIB-IV resectable MEL who received adjuvant or neoadjuvant treatment with anti-PD-1 therapy were enrolled from the University of Pittsburgh Melanoma Center biospecimen repository. The association between irAEs/immunosuppressive therapy and recurrence-free survival (RFS) and overall survival (OS) were evaluated by univariate and multivariate Cox proportional hazards regression models. Results: A total of 6059 PT were consented to the repository: stage III = 1,328, stage IIB = 403, and stage IIC = 269 PT. Of these PT, 180 men and 93 women received adjuvant anti-PD-1 therapy. Average age at diagnosis was 61. BRAF mutation present in 94 PTs: V600E = 71 PT, V600K = 11 PT. Documented irAEs occurred in 50.9% of PTs. Cutaneous irAEs were most common (65/139, 46.8%), followed by endocrine (45/139 32.4%), and visceral organ (37/139, 26.6%). Of the 32 visceral organ irAEs, 15 were gastrointestinal, 10 pulmonary, 5 hepatic, and 1 renal. Systemic corticosteroids > 10mg of prednisone equivalent were administered during adjuvant therapy for 24.9% of PT. In the univariate model, development of irAEs was associated with improved OS (HR = 0.38; CI 0.18-0.83, p = 0.015). In a multivariate analysis after adjusting for age and sex, irAE development continued to be associated with improved OS (HR = 0.38; CI 0.17-0.82, p = 0.014). RFS did not differ for patients that developed irAEs (HR = 0.9; CI 0.59-1.4, p = 0.67). Steroid treatment was not associated with a change in OS (HR = 1.04; CI 0.46-2.4, p = 0.93) or RFS (HR = 0.96; CI 0.59-1.56, p = 0.87). Conclusions: Half of stage IIB-IV resectable MEL PT receiving adjuvant anti-PD1 therapy developed irAEs, of which 24% required steroid therapy. Development of irAE was associated with improved OS and corticosteroid use for irAE did not mitigate adjuvant therapy outcome benefits.
Early ctDNA reduction may identify patients with stable disease and long OS on tebentafusp.
Authors: Feng Dan , Collins Laura , Callahan Margaret K. , Sullivan Ryan J. , Piperno-Neumann Sophie , Nathan Paul D. , Hassel Jessica Cecile , Goodall Howard , Holland Chris , Ranade Koustubh , Shoushtari Alexander Noor 
Published: June 2023

9589 Background: Tebentafusp, a bispecific (gp100 × CD3) ImmTAC showed significant overall survival (OS) benefit (HR 0.51) versus investigator’s choice in a Phase (Ph) 3 trial in first line (1L) HLA-A*02:01+ adult patients (pts) with metastatic uveal melanoma (mUM) [Nathan NEJM 2021]. In Ph2 and Ph3 trials of tebentafusp, OS was improved regardless of RECIST best response and the degree of early reduction in ctDNA was a better predictor of OS [Carvajal Nat Med 2022; Sullivan AACR 2023]. Here we explored whether early on-treatment reduction in ctDNA could distinguish pts with stable disease (SD) and long OS vs those with SD and short OS in a Ph3 trial of tebentafusp in 1L mUM pts. Methods: 1L HLA-A*02:01+ pts with mUM received 68 mcg tebentafusp weekly intravenously after intra-patient dose escalation (NCT03070392). Response was assessed by investigators per RECISTv1.1. Sera collected at baseline (BL) and week 9 on tebentafusp were analyzed for ctDNA using targeted mPCR-NGS assay for mutations in 15 genes including GNAQ, GNA11, SF3B1, CYSLTR2, PLCB4 and EIF1AX. Landmark OS from week 9 was analyzed in subsets with ≥0-3 log reductions in mean tumor molecules (MTM) per ml of serum on treatment. Data cutoff 11-Nov-2022. Results: 76/245 (36%) tebentafusp-treated pts had best response of SD, with a median OS of 29 months and were evaluable for ctDNA. Baseline tumor burden as assessed by sum of longest lesion diameters and percentage of pts with elevated BL serum LDH were greater in the subset with < 1 year (yr) OS (median 70 mm and 64%, respectively) than in subsets with OS ≥ 1 yr (median 42 mm, 11%) or OS ≥ 2 yrs (median 31 mm, 9%). Almost half (36/76; 47%) of all SD pts had detectable ctDNA mutations in one or more UM genes at baseline. Baseline ctDNA levels were similar across survival groups. By week 9 on-treatment, ctDNA reduction was observed in 34/36 (94%) evaluable SD pts, including 29/36 (81%) with ≥ 0.5 log reduction, 18/36 (50%) with ≥ 2 log reduction and 16/36 (44%) with undetectable ctDNA (clearance). Deeper reductions in ctDNA were associated with better OS (Table). Conclusions: In this Ph3 trial, ctDNA reduction by week 9 on tebentafusp was strongly associated with improved OS in pts with best RECIST SD. Early ctDNA reduction may predict SD patients with long OS on tebentafusp. [Table: see text]
Evolution of breast cancer management in the Dominican Republic in the 21st century.
Authors: Molaire Robens , Monanci Miguel , Hidalgo Dayanara 
Published: June 2023

e12500 Background: Breast cancer is a major public health problem. Despite knowing the management, clinicians are forced to provide less than optimal care when diagnostic and/or treatment are lacking. For that, we decided to do a review about breast cancer treatment during the 21 st century in Dr. Heriberto Pieter Oncology Institute. Methods: A retrospective study was done to describe and evaluate the management of patients with breast cancer. A random sample of 100.00 patients was selected, which was reduced to 64.00 after the inclusion-exclusion criteria application like lacking immunohistochemistry, partial treatment. and less than 5 years with the diagnosis. Results: Molecular subtypes included luminal A: estrogen receptor+ and/or progesterone receptor+, Her2Neu3- (44%); luminal B: estrogen receptor + and/or progesterone receptor +, Her2Neu 3+(9%); Her2Neu 3: estrogen receptor-, progesterone receptor -, Her2Neu 3+ (19%); basal-like: estrogen receptor-, progesterone receptor-, Her2Neu3- (28%). Chemotherapy history: 63% with neoadjuvant chemotherapy; 78% with adjuvant chemotherapy, 18.75% as primary and 59.37% as secondary; 17% with palliative chemotherapy, 3% as primary and 14% as secondary. Surgical history: 31% with primary modified radical mastectomy (MRM), 63% with secondary MRM, and 2% with quadrantectomy. Radiotherapy: 11% with primary radiation therapy (RT), 36% with secondary RT, and 3% with palliative RT. Hormonal therapy of patients: 33% with tamoxifen, 11% with aromatase inhibitors, 8% with combination of hormonal therapy, and 22% with extended adjuvant hormone therapy of more than 5 years. Primary endpoints were disease-free survival at 5 years (67%), objective response rate to neoadjuvant chemotherapy (100% according to RECIST criteria), and overall survival at 5 years (87.5%). Currently in Dominican Republic there is availability of more target therapy for Her2Neu3 like pertuzumab, lapatinib, other drugs for positive hormone receptor named CDK4/6 inhibitors (palbociclib, ribociclib), olaparib for germline BRCA mutation and pembrolizumab for basal like or triple negative breast cancer (TNBC). Finally, according to the latest World Health Organization (WHO) data published in 2020, breast cancer deaths in Dominican Republic reached 1,460 or 2.14% of total deaths. The age adjusted death rate is 28.28 per 100,100 and the number of new cases in 2020 for breast cancer was 3,412 (17.2%). Conclusions: This review allows us to track the evolution of breast cancer management in Dominican Republic during the 21st century. It highlights the efforts made to apply guidelines on breast cancer management in general and global objective response to neoadjuvant regimen. It also highlights the need to implement more primary prevention and early detection since 52% of patients belong to the locally advanced category. [Table: see text]
Management of adjuvant endocrine therapy (AET) side effects in patients with breast cancer: A single cancer center experience.
Authors: Kuhn Elaine Patricia , Pirruccello Jonathan P. , Stone Simon , Tosteson Tor D , Schwartz Gary N. , Chamberlin Mary D. 
Published: June 2023

e12503 Background: Up to 50% of breast cancer survivors are unable to complete the recommended 5-year course of adjuvant endocrine therapy (AET), usually due to side effects. Patients who develop side effects may change to a different medication (‘switch’) or may treat side effects with additional medications or non-pharmacologic strategies. While there are numerous evidence-based treatments available for side effects of AET, the benefit of switching AET is less well known. We have previously reported on the association between switching and early discontinuation of AET. Here, we provide further insight into the use of switching vs side effect management at our cancer center. Methods: We conducted a retrospective chart review of patients diagnosed between 2011-2014 with early stage, ER+/HER2- breast cancer. Clinical data extracted by chart review included side effects and treatment history. Patients were grouped based on whether they received a switch vs side effect management and compared for variables of interest using Chi-squared tests and confidence intervals. Multiple logistic regression was used to assess long-term adherence, adjusting for side effect type and severity. Results: A total of 228 patients with early-stage ER+/HER2- breast cancer were evaluated. Among them, 162 patients (71.0%) received treatment for side effects. A medication switch was offered in 98/162 (60.5%) cases, with side effect management (SEM) alone offered in the remaining (39.5%). Patients who switched were more likely to have reported severe side effects compared to patients who received SEM alone (OR 4.56, 95% CI (2.1, 9.8), p < 0.001). Hot flashes were more frequent in patients who received SEM compared with those switching (89% vs 59%, respectively, p < 0.001), while arthralgias were more frequent in the patients who were offered a switch (70% vs 47%, p = 0.002). ‘Other’ side effects were also more frequent in patients who switched (58% vs 30%, p < 0.001). Among patients who discontinued therapy early, the majority did so within the first 12 months (18/43, 42%). The long-term adherence rate was 73% overall, and it was significantly lower in the subset of patients who received a switch compared to those who received SEM – 62% vs 91% respectively, p < 0.001. Significance was maintained after adjusting for side effect type and severity with multiple logistic regression, p = 0.013. Conclusions: Despite limited evidence, rates of switching are high in clinical practice. Switching is more common in patients with severe symptoms, and those who report arthralgias and uncommon side effects. Switching was associated with poor long-term adherence. Due to the potential for selection bias, conclusions are limited as to whether switching itself is ineffective. A prospective randomized trial is under development at our cancer center to address this question.
Re-referral for post-op radiation in elderly breast cancer patients who initially omit RT but are unable to tolerate endocrine therapy.
Authors: Kaleem Tasneem , Brampton Shelley 
Published: June 2023

e12507 Background: Omission of Radiation in the setting of Elderly patients 70 yo and above with ER+, cN0, pT1 tumors who receive adjuvant endocrine therapy (HT) is standard of care per NCCN. However, the average adherence rate of HT ranges from 41% to 72%, which is not optimal for patient outcomes. In our institution, we evaluated the treatments of all patients who qualified for omission of radiation upfront and the number of re-referrals for adjuvant radiation in Elderly Breast cancer patients who were unable to tolerate HT past 6 months. Methods: Data was obtained through the National Cancer Registry at our institution for 2021 and reviewed mid 2022. Inclusion criteria included patients diagnosed with Pathologically Invasive Breast Cancer AJCC Stage I-IIB age 70 and above. A total of 176 patients were eligible for review. 86 patients did not qualify for inclusion into study due to 7 receiving surgical treatment outside our system. Furthermore, 81 patients did not qualify due to the following reasons or combination: Mastectomy (19), Triple Negative, Greater than 2 cm, N+, AI only. A total of 90 patients qualified for omission and review. Six month HT therapy cut off was extrapolated by Barbieri et al who determined a 6 month delay of RT after surgery was not associated with an increased risk of relapse. Results: From the 90 patients who qualified for omission of radiation, 67 % (n = 60) of patients chose radiation omission, 30% (n = 27) of patients chose upfront radiation, and 3% (n = 3) of patients declined all therapy. Of the 60 patients who chose omission, 87% of patients had continued HT, however 2 patients passed away within 1 year of surgery. A total of 13% of patients (n = 8) who omitted radiation did not go past 6 months of HT, and only 2 out of 8 patients (25%) were referred back to radiation oncology and moved forward with treatment. For the 27 patients who chose radiation upfront even though they qualified for omission, the most common reason per records was the patient was unsure after initial multidisciplinary clinic that they would be able to tolerate HT. Interestingly, 27% of these patients ended up stopping HT within 9 months due to side effects. Conclusions: Omission of radiation is an option for Elderly Early stage breast cancer patients in the setting of HT. However, HT compliance is variable due to side effects. In our one year single institution study, only 25% of patients who omitted RT and did not get past 6 months of HT were sent back for radiation. We encourage an increased awareness and communication between Radiation Oncology and Medical Oncology regarding the option of radiation for patients who do not pass 6 months of HT. Our institution has implemented an Epic message system and Breast Navigation to aid in re-referral. It is also imperative at the time of Radiation Oncology consultation to discuss the possibility of intolerance to HT in the setting of omission may indicate radiation therapy at a later date.
Amelioration of acute radiation dermatitis in patients with breast cancer by a bioadhesive barrier-forming oral gel (Episil): A single-center, open, parallel, randomized controlled trial.
Authors: Li Qian , Ning Fangling , Liu Changmin 
Published: June 2023

e12519 Background: Episil is a bioadhesive barrier-forming oral liquid gel that can relieve mucositis caused by radiotherapy (RT) and hence relieves pain effectively.The purpose of this trial is to compare the efficacy and safety of Episil in improving acute radiation dermatitis in breast cancer patients. Methods: Key eligibility criteria were as follows: Pathologically confirmed breast cancer; female ≥18 years of age; planning to receive postoperative radiation therapy; surgery with modified radical or breast-conserving surgery; fully healed surgical incision; intact skin in the irradiated area; KPS score ≥80; no severe endocrine or metabolic disease; voluntary participation and signed informed consent; ability to read and understand and good compliance. The primary endpoint was the grading of radiation dermatitis during treatment. Results: A total of 102 patients were included from January 2022 to December 2022. The patients were grouped in a 2:1 ratio by randomized number table method, 67 patients received Episil combined with conventional skin care and 35 patients served as the control group receiving conventional skin care only. Two patients in the Episil group dropped out halfway. According to the RTOG grading, the skin reaction rate and the degree were significantly better in the Episil group than control group (24.62%, 72.31%, 3.08, 0, 0 VS 0, 85.71%, 14.29%, 0, 0, 0) in the 0, 1, 2, 3 and 4 grades respectively (P<0.001). And the pruritus score was significantly lower in the Episil group than in the control group (P<0.05). The results of the EORTC QLQ-C30 Quality of Life Questionnaire showed that the overall health (P<0.05) and overall quality of life (P<0.05) were better in the Episil group than control group after radiotherapy. Relative to the control group, the Episil group produced significantly lower rates of stress, anxiety, and depression (P<0.05) and had less impact on family life and social activities (P<0.05). Most importantly, the Episil group produced fewer pain reactions after the end of radiotherapy. Conclusions: In breast cancer patients receiving radiotherapy, Episil may significantly reduce the grading of acute radiation dermatitis, reduce patient symptoms, and improve patient quality of life. Clinical trial information: ChiCTR2200059646 .
Therapy decision-making after pre-operative endocrine therapy in HR+ HER2- early breast cancer.
Authors: Sorokina Irina , Ignatieva Maria , Kolyadina Irina Vladimirovna , Kvetenadze Gurami , Ivanyuk Maria , Gorbunova Maria , Zhukova Lyudmila 
Published: June 2023

e12520 Background: Nowadays, the right way for therapy decision-making in HR+ HER2- early breast cancer (BC) includes the complex of validated multigene assays (VMA) result with clinical and IHC evaluation. Given the inability to use VMA in routine clinical practice, the short-term pre-operative endocrine therapy (P-ET) allows to estimate more precisely plan the further adjuvant therapy (AT) in the patients (pts) with early HR+ HER2- BC. Our work is aimed to share of pts with P-ET benefit, or tumor phenotype reversion for proper treatment planning in pts with early HR+ HER2- BC. Methods: HR+ HER2- BC pts stages I-II any level of Ki67 and any grade (G) have received P-ET (letrozole (L)/anastrozole (A)/tamoxifen (TAM)) no less than 2 weeks until surgery in A.S. Loginov MCSC, Russia. Enrollment period was Jun’20 - Jan’23. The study was aimed to access P-ET efficiency in pts with baseline Ki67>10% downgrading to ≤10% (1), tumor ET sensitivity in the whole group (2) and/or phenotype transformation during P-ET followed by changing AT strategy (3). Results: At the data cut-off (Jan’23) 998 pts (5 pts were men) with HR+ HER2- BC were enrolled with median age 63,5 (range:26-85). The median time of P-ET was ≈19,5 days (range: 14-42). Pts flow according to tumor Ki67 level dynamic is show. 54% (434) pts with initially Ki67 level >10% decreased Ki67≤10% after P-ET in whom 36% (314) pts avoided adjuvant chemotherapy. In Ki67≤10% baseline group (n=187) tumor Ki67 level after P-ET increased >30% in every fifth case (n=35, 19%), that may reflect the initial ET resistance. Ki67 level dynamic change under P-ET was observed regardless of the TAM/IA use. 4% (38) pts has resulted the phenotype change to HER2+ BC (n=32) and TNBC (n=6) with subsequent AT decisions (anti-HER2-based or dose dense regimens, respectively). In this group there weren’t any Ki67 decrease after P-ET that additionally confirms the unmet need for treatment plan correction. Conclusions: In HR+ HER2- BC pts the results of P-ET with TAM or IA before surgery helps to estimate pts prognosis and further AT strategy: to identify the pts population of whom chemotherapy can be avoided while maintaining treatment efficacy with a better quality of life (1), to assess the initial ET tumor sensitivity (Ki67 baseline level independently) (2), to radically change the planned AT to achieve optimal treatment results (3). Mature data of long-term pts outcome are awaited. [Table: see text]
The use of minimal residual disease in patients with high-risk breast cancer.
Authors: Kameoka Alyssa , Fukui Jami Aya 
Published: June 2023

e12521 Background: Breast cancer is the most frequently diagnosed cancer worldwide and the second leading cause of cancer death in women in the United States. Despite being disease-free after primary treatment, studies have shown that up to 30% of patients present with disease recurrence. Circulating tumor DNA (ctDNA) in blood is a minimally invasive technique to characterize individual cancer biology and monitor disease. Previous studies have demonstrated that ctDNA can be a sensitive and specific approach to breast cancer follow up and surveillance of disease recurrence for all subtypes. Methods: We evaluated 38 high risk breast cancer patients utilizing a personalized and tumor-informed ctDNA assay at 3-6 month intervals. We defined high risk as: any stage III disease, triple negative breast cancer (TNBC) or HR-/HER2+ breast cancer who received neoadjuvant chemotherapy treatment (NACT), pregnancy associated breast cancer, metastatic breast cancer without any evidence of disease, history of bilateral breast cancer, high risk genetics (i.e. BRCA1 or BRCA2 mutations), young age at diagnosis (<40 years old) and/or breast cancer recurrence of any subtype. Results: Patient ages ranged from 34 to 83 (average: 53.3 years old) and included a diverse race/ethnicity population: White (n=12, 31%), Japanese (n=9, 23.7%), Native Hawaiian (n=6, 15.8%), Chinese (n=4, 10.5%), Filipino (n=4, 10.5%), Black (n=1, 2.6%), Hispanic (n=1, 2.6%), and Korean (n=1, 2.6%). Of the 38 cases, there was one ctDNA positive finding seen in a high risk case (young age at diagnosis and BRCA2 mutation) of clinical stage IIA HR+/HER2- breast cancer. After NACT, bilateral mastectomies, and radiation, patient remained on tamoxifen (declined ovarian function suppression) and was initially ctDNA negative until a second test identified detectable ctDNA. Restaging scans however did not show any evidence of disease. A third ctDNA test three months later, continued to be positive without any evidence of disease. All other cases showed negative ctDNA testing with an average of 1.55 ctDNA tests done per patient over two years. However, one case of clinical stage IIB TNBC had contralateral recurrence despite negative testing. After receiving NACT, bilateral mastectomies, post-operative paclitaxel and radiation, two ctDNA tests done three months apart were negative. Conclusions: There is potential use for this ctDNA platform in high risk breast cancer patients but larger studies need to be done. [Table: see text]