bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic profile of Japanese patients with rare ductal adenocarcinoma of the prostate has high grade and poor prognostic aspects.
Authors: Kosaka Takeo , Kobayashi Hiroaki , Nakamura Kohei , Baba Yuto , Yasumizu Yota , Matsumoto Kazuhiro , Ito Keiichi , Nishihara Hiroshi , Oya Mototsugu 
Published: July 2024

e17046 Background: Ductal adenocarcinoma (DAC) is a rare subtype of prostate cancer with unknown etiology and poor prognosis. Genomic profile analysis using next-generation sequencing has the potential to elucidate the pathogenesis of rare cancers. To date, some studies have investigated the genetic profile of the DAC genotype; however, no definitive findings have been obtained due to the small number of patients and limited geographic coverage. The discovery of novel prognostic biomarkers and identification of new pharmacotherapeutic targets for DAC are currently of research interest. The aim of this study is to analyze the genomic profile of DAC in a Japanese population and to summarize its features. Methods: Clinical and histopathological records from our three hospitals were searched for radical prostatectomy, transurethral resection of the prostate, and prostate needle biopsy specimens containing a DAC component in the past 10 years. Twenty-eight patients diagnosed with DAC of the prostate were identified, of whom 15 were eligible for genomic profile analysis and 10 patients (66.7%) had the pure type. Genomic evaluation was performed using either the FoundationOne CDx or PleSSision testing platform. Results: At least one genomic alteration occurred in 14 patients (93.3%), and the most frequently mutated gene was tumor suppressor protein p53 ( TP53), which was found in seven cases (46.7%). Additionally, five cases (33.3%) had mutations in retinoblastoma transcriptional corepressor 1 ( RB1), and all these patients had the pure type. Four cases had both TP53 and RB1 alterations, and most of these possessed the pure type and had PSA levels of less than 4.0. Compared to previous study results, the frequency of genetic alterations in the phosphoinositide 3-kinase (PI3K) pathway (n = 3; 20.0%) and Wnt-β/catenin pathway (n = 6; 40.0%) was comparable, but alterations in the DNA damage repair (DDR) pathway were few (n=1; 6.7%). None of the patients presented high tumor mutation burden or microsatellite instability. Conclusions: We found that the Japanese cohort with DAC has unique features such as high frequency of alterations in tumor suppressor gene such as TP53 and RB1, and few DDR pathway alterations, suggesting the existence of regional and racial differences in genomic profiles. Genomic analysis using next-generation sequencing is expected to be useful in elucidating the pathogenesis of DAC, and further accumulation of cases is considered important.
Patient characteristics, treatment patterns and early trends of lutetium Lu 177 vipivotide tetraxetan (177Lu-PSMA-617) use by US urologists and oncologists.
Authors: Nguyen Jennifer , Patel Jeetvan , Kang Barinder , Yu Channing , Sawhney Amrita , Fallick Mark , Gorritz Magdaliz , Chen Chi-Chang , Paltanwale Queenie , Sun Kainan , Shore Neal D. 
Published: July 2024

e17048 Background: 177Lu-PSMA-617 was approved by the US Food and Drug Administration in March 2022 for the treatment of patients with prostate-specific membrane antigen (PSMA) positive metastatic castration resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition (ARPI) and taxane-based chemotherapy. This study describes characteristics of patients treated with 177Lu-PSMA-617, treatment patterns and early trends in 177Lu-PSMA-617 utilization by US urologists (URO) and medical oncologists (ONC). Methods: This retrospective cohort study identified adult patients with ≥1 claim for 177Lu-PSMA-617 between 3/1/22 and 6/30/23 (first claim = index date) from the IQVIA open-source pharmacy and medical claims database. Patients were grouped by the physician specialty of the treating/referring physician. Patient characteristics were assessed within the 6 months prior to 177Lu-PSMA-617 initiation. Prior prostate cancer treatments were assessed over all available pre-index data. Results: Overall 1,394 patientstreated with 177Lu-PSMA-617 were identified during the first 16 months post-approval; 76.9% treated by an ONC and 23.1% treated by a URO. The mean age overall was 72.1 years; most patients were aged 65 and older (ONC, 83.3%; URO, 84.8%). Most patients had bone metastases (ONC, 88.0%; URO, 86.3%) and over one-third had visceral metastases (ONC, 34.6%; URO 35.7%). URO treated a higher proportion of patients with only lymph node metastases (5.9%) than oncologists (2.6%). Prior to 177Lu-PSMA-617, the vast majority of patients received ARPI and/or taxanes (ONC, 88.2%; URO, 89.4%). Use of 177Lu-PSMA-617 has steadily increased over the 16 months since approval with over five times as many patients being treated by ONC and URO in the first half of 2023. Conclusions: This is the first large-scale study describing 177Lu-PSMA-617 patient characteristics, prostatic cancer metastatic distribution, treatment patterns, and utilization trends by prescriber type (ONC and URO). This study highlights how URO are playing a pivotal role in management of post-taxane mCRPC patients receiving 177Lu-PSMA-617. As additional data with 177Lu-PSMA-617 becomes available, we anticipate the role of URO to significantly evolve with the potential for earlier use of 177Lu-PSMA-617 for pre-taxane mCRPC patients.
High-dose furmonertinib in combination with intraventricular chemotherapy for EGFR exon 20 insertion mutated lung adenocarcinoma with leptomeningeal metastasis.
Authors: Fang Shencun , Fang Hehui , Xu Ting , Yang Liangfeng , Wang Xiaoyue , Liu Na , Zhang Xing , Zhang Bei 
Published: July 2024

e20555 Background: Leptomeningeal metastasis (LM) is a severe complication of advanced lung adenocarcinoma (LUAD) and always has a dismal prognosis. EGFR exon 20 insertion ( EGFR 20ins) is the third most common EGFR mutations; however, there are currently no reports focusing on LM with EGFR 20ins, and the optimal therapy for these patients remains unclear. This retrospective study aimed to evaluate the efficacy and safety of high-dose furmonertinib in combination with intraventricular chemotherapy in EGFR 20ins mutated LUAD patients with LM. Methods: Weretrospectively enrolled 10 LUAD patients with LM who had failed multiline treatment between May 2021 and June 2023 at Nanjing Chest Hospital. All of them had confirmed EGFR 20ins by next generation sequencing. All patients received furmonertinib in combination with intraventricular chemotherapy via the Ommaya reservoir. Furmonertinib was taken at 160 mg once daily. The chemotherapy regimen consisted of 30mg pemetrexed and 5 mg dexamethasone administered twice weekly for 2 weeks during the consolidation phase, followed by a maintenance phase every 3-4 weeks until disease progression or unacceptable toxicity, or patient refusal. Results: The median age was 53.5 years (range: 39-66), and six (60%) were males. Four patients (40%) had an ECOG of 3, and six patients (60%) had an ECOG of 4. The intracranial ORR (iORR) was 60% (6/10) and intracranial DCR (iDCR) was 90% (9/10). The ECOG PS improved in 80% patients after treatment. With a median follow-up of 9.3 months, the median intracranial progression-free survival (iPFS) was 7.3 months (95% CI, 3.3-NR) and the median overall survival (OS) was 8.8 months (95% CI, 4.9-NR), respectively. Treatment related adverse events of ≥ grade 3 occurred in only 2 patients, which were nausea and rash. Conclusions: Furmonertinib in combination with intraventricular chemotherapy is a tolerable treatment with breakthrough clinical efficacy for LUAD patients with LM harboring EGFR 20ins.
Impact of timing of immunotherapy in survival among patients with advanced lung adenocarcinoma treated with first-line immunochemotherapy: A propensity score matching.
Authors: Sun Yanxin , Wang Leirong , Sun Yuping , Dang Qi , Ge Yihui , Gao Aiqin , Cheng Qinglei , Sun Haifeng , Zhang Jian , Wu Jiake , Li Juan 
Published: July 2024

e20560 Background: Immunochemotherapy combinations have been the mainstream first-line standard treatment of advanced non-small cell lung cancer (NSCLC), wherein concurrent chemotherapy and immunotherapy are conventionally fixed to an established dosing regimen. Few studies had suggested the remarkable impact of the timing of immunotherapy on immunochemotherapy combined therapy. However, this issue has not been addressed in advanced NSCLC cohort. Methods: This study was a retrospective analysis of 532 patients with advanced lung adenocarcinoma (LUAD) without EGFR/ALK mutations who underwent immunochemotherapy as first-line systemic treatment between June 2018 to June 2022 at 3 facilities. Patients were divided into two groups (induced and non-induced) according to the different timing of immunotherapy in combined therapy, which defined induced as receiving 1 or more cycles of full-dose chemotherapy alone before concurrent immunochemotherapy. The bias between induced and non-induced groups was minimized with Propensity Score Matching (PSM). Patients outcomes, including progression-free survival (PFS) and overall survival (OS), were compared between the two groups by Kaplan-Meier survival curves and Cox regression analyses. Results: Survival analysis showed that both PFS and OS of the induced chemotherapy group patients were significantly longer than that of non-induced group (PFS: 14.63 months vs. 10.13 months, p = 0.004; OS: Not reached vs. 20.27 months, p = 0.0013). In the COX regression, after adjusting for confounders, induction chemotherapy was found to be a remarkable favorable factor for both PFS and OS (PFS: HR = 0.73, p= 0.018; OS: HR = 0.69, p= 0.034). After pretreatment features and treatment parameters were included in PSM, 104 patients were identified in each groups with matched characteristics, and moreover, the results of survival analysis remained consistent and showed significant difference between induced and non-induced group (PFS: 14.63 months vs. 10.23 months, p = 0.029; HR = 0.71, p= 0.030. OS: Not reached vs 18.27 months, p = 0.0013; HR = 0.52, p= 0.002). Conclusions: For advanced LUAD patients treated with first-line immunochemotherapy combinations, the timing of immunotherapy had significant impact on prognosis, which suggested notable benefit of induction chemotherapy before concurrent immunochemotherapy.
Mapping incidence and survival of non-small-cell lung cancers stratified by mutation type in southern Appalachia: A single center retrospective study.
Authors: Natarajan Arjun , Roman Hernandez Erica Marie , Ramineni SriVyshnavi , Liu Jieying , Sackfield Brad , Shastri Dipsa , Costello Patrick , Chakraborty Kanishka , Lewis Nicole 
Published: July 2024

e20568 Background: Non-small cell lung cancer (NSCLC) is often a mutation-driven disease with variability in incidence and survival depending on location as seen in population-based cohort studies. Our study aims to delineate these differences based on molecular testing for these mutations in our study cohort at East Tennessee State University - Quillen College of Medicine, which is based on patients from east Tennessee, western North Carolina, and southwestern Virginia. Methods: We obtained pathology results of 294 patient samples with advanced/metastatic NSCLC from our cancer center/health system database over a 5 year period. PDL-1 was tested in all patients. Fluorescent in-situ hybridization (FISH) testing for common pathogenic driver mutations such as EGFR, ALK, ROS1, RET, MET and PTEN were performed as is standard of care. Molecular sequencing was performed and included over 40 genetic mutations and 2 biomarkers, several of which today are considered targetable for advanced NSCLC, per standard of care. Incidence of different mutations was measured in our patient population. Overall survival was calculated with date of diagnosis available based on pathology report and date of patient expiration obtained from electronic medical records. Data analysis was performed to ascertain which mutations carried an increased risk of death. Results: The TP53 mutation was very common, seen in 85% of squamous cell carcinoma (SCC) histology and 55% of adenocarcinoma. Similarly, incidence of PTEN deletion by FISH was noted to be 52% in SCC and 31% in adenocarcinoma. EGFR mutations were rare, seen in only 3% of tested patients. We had an incidence of KRAS G12C mutations at 11% overall, but it was present in up to 18% of adenocarcinomas. BRAF was seen in 4.8% of all cases, 8% of adenocarcinomas and 2% of SCC. Since there were more than 2 predictors, Cox proportional-hazards regression model was fit. Due to either having all negative values or very few positive values, the variables CCND1, CDKN2B, ERBB2, ERBB4, FGFR, FGFR2, MET, MSI, NRAS, PDGFRA, RET, RS01, SCR were excluded from analysis. A total of 156 samples were used in final analysis. After model building, it was found that BRAF and KRAS G12C mutation were significant predictors of survival by hazard ratios for death. Conclusions: In our unique patient population, there was a greater incidence of deleterious TP53 mutations and PTEN deletions compared to the general North American advanced/metastatic NSCLC population. Although BRAF and KRAS G12C mutations were not at a greater incidence in comparison to the rest of North America, they were notably significant predictors of survival, conferring nearly 3.4 and 2.7 times increased risk of death in our study. [Table: see text]
Prognostic nomogram for overall survival in patients with stage IV non-small cell lung cancer treated with chemotherapy combined with high-dose thoracic radiotherapy.
Authors: Geng YiChao , Su Shengfa , Ouyang Weiwei , Hu Yinxiang , Li Qingsong , Ma Zhu , Luo Daxian , Yang Wengang , Chen Xiaxia , Hu Cheng , Lu Bing 
Published: July 2024

e20607 Background: Although the targeted therapy and immunotherapy have become the first line options for selected stage IV non-small cell lung cancer (NSCLC) patients. However, there are instances where certain patients are not administered targeted therapy or immunotherapy due to a variety of factors, chemotherapy and radiotherapy remain the main way to treat such patients. This study aimed to construct a prognostic nomogram for patients with stage IV NSCLC treated with chemotherapy combined with high-dose (≥ 60 Gy) thoracic radiotherapy. Methods: The nomogram was based on a retrospective study of 335 patients with stage IV NSCLC who treated with chemotherapy combined with high-dose (≥ 60 Gy) thoracic radiotherapy were hospitalized between January 2010 and January 2018(patient did not receive TKI therapy or immunotherapy). The patients were randomly assigned to either a primary cohort (n = 234) or a validation cohort (n = 101) at a ratio of 7 : 3. In the primary cohort, a univariate analysis of the clinical or therapeutic factors that may predict OS was performed using a Cox regression model, with P < 0.05 indicating statistical significance. The variables from the univariate analysis that affected OS significantly were included in the Cox regression model for the multivariate analysis. A nomogram was then created based on the results of multivariate analysis and using the “rms,” “foreign,” and “survival” R version 4.0.3 software packages. The discriminatory ability of the nomogram was measured using the area under the curve (AUC) of a receiver operating curve (ROC). Results: Multivariate logistic regression analysis revealed that malignant pericardial effusion, adrenal metastasis, elevated lactate dehydrogenase levels, and excessive planning target volume were independent risk factors for poorer 1–3 year overall survival (OS), while a higher radiotherapy dose for the primary lesion was associated with better OS. Nomogram prediction models were constructed using these five variables. The AUC of the ROC for 1-year, 2-year, and 3-year OS in the primary cohort were 0.685, 0.729, and 0.816, respectively. In the validation cohort, the AUC of the ROC for 1-year, 2-year, and 3-year OS were 0.706, 0.749, and 0.797, respectively. The Kaplan-Meier survival analysis showed that differentiation between the high-risk group and low-risk group using the prediction model had a direct, significant effect on survival in both the primary cohort ( P < 0.001) and validation cohort ( P = 0.004). Conclusions: The nomogram model constructed in this study may be used to objectively predict the prognosis and OS of patients with stage IV NSCLC treated with chemotherapy and high-dose thoracic radiotherapy. Identify patients who may not benefit from high-dose thoracic radiotherapy prior to treatment to avoid overtreatment.
Impact of a 1-day disease overview session on knowledge and preparedness for incoming hematology/oncology fellows.
Authors: Pywell Cameron , Gahagan Andrew , Paschal Rita Daniell 
Published: July 2024

e21011 Background: The start of hematology/oncology fellowship involves an abrupt transition in disease management and a steep learning curve. Many fellowship programs have introductory lecture series over the first weeks or months, but fellows often need specialty knowledge prior to the completion of these. Methods: A 1-day session for incoming first year fellows at our institution was developed to provide brief overviews of common conditions in classical hematology, malignant hematology, and oncology, subdivided into a total of 12 topics. Fellows were surveyed before and after the session regarding their feelings of preparation for fellowship and having good disease frameworks for each of the 3 major content areas. Fellows also evaluated the content and length of each topic. Pre- and post-course knowledge assessments were conducted. Feedback was sought later in the year as well. Results: The session was well-received by fellows. Post-course assessments increased by a mean of 32% (SD 6%). The majority of topics were well-reviewed for length and content. Fellow responses to feelings of preparedness and disease frameworks were improved or unchanged from pre-course surveys. All fellows agreed that it was a good use of their time and would recommend it being a part of future orientation sessions. Fellows recommended splitting the session into 2 days. Conclusions: A 1-day introductory course for incoming hematology/oncology fellows is feasible and rapidly improves baseline knowledge to prepare fellows for clinics, consults, and being on call.
Causes of death and patterns of metastatic disease at the end of life for patients with advanced melanoma in the immunotherapy era.
Authors: Lee Daniel , Yang Alexander , McNamara Madeline , Kluger Harriet M. , Tran Thuy , Olino Kelly , Clune James , Sznol Mario , Ishizuka Jeffrey Joseph 
Published: July 2024

e21522 Background: Despite the drastic improvement in survival of patients with metastatic melanoma from immune checkpoint inhibitors (ICIs), almost half of patients still die from their disease. Factors surrounding death including mechanisms of death, sites of disease, and settings of death remain poorly described. A better understanding of these factors is paramount to optimize management for these patients. Methods: A retrospective observational cohort study was performed for patients age > 18 who died after treatment for advanced melanoma with anti-PD1 therapy or ipilimumab + nivolumab (Ipi/Nivo) at Yale Cancer Center (YCC) between 1/2009 and 6/2023. Primary outcome was cause of death. Statistical analyses were performed with Stata SE, version 15.0 (StataCorp, College Station, TX). This study was approved by the Yale Institutional Review Board (Protocol #2000034631). Results: Overall, 287 patients with melanoma who received ICIs were documented to be deceased; 183 met inclusion criteria. Median time from metastatic diagnosis to death was 16.1 mos (range 0.3 to 135.1 mos). Median age at death was 70 (range 22-101), 62.8% were male, and 90.2% were white. Most patients (52.5%) received Ipi/Nivo first line, and 79.8% of patients received both anti-PD1 and anti-CTLA4 treatment at some point. The median number of metastatic sites at death was 4 (range 0-13). The majority (90.1%) of patients with measurable disease had multi-system involvement of melanoma. Eleven patients had no evidence of disease at death and died due to non-melanoma causes. The most common sites of metastatic disease at death were distant lymph nodes (62.8%), lung (57.9%), liver (50.8%), brain (38.8%), and bone (37.7%). In total, 80.3% (147/183) experienced hospitalization within 3 months prior to death or hospice enrollment. Most died in the hospital (31.7%) or while enrolled in hospice (31.2% inpatient vs. 29.4% home). Overall, 10.9% of patients had survival > 5 years after metastatic diagnosis; 76.2% of long-term survivors died due to melanoma. Of 174 patients with evaluable causes of death, 87.9% of deaths were due to melanoma (Table 1). Patients with pleural metastases were more likely to die of respiratory failure (p = 0.036, OR 2.41 95% CI 1.06-5.50). Conclusions: The majority of deaths were a consequence of metastatic melanoma, with the most common causes including FTT, respiratory failure, and infection. [Table: see text]
Correlation of previous local vaccination site “flares” during immunotherapy for metastatic melanoma with complete responses to therapy.
Authors: Loo Kimberly Leticia , Ma Barbara Ting-wen , Pavlick Anna C. 
Published: July 2024

e21534 Background: mRNA vaccines have been shown to stimulate T-cells targeting patient-specific tumor neoantigens. When combined with immune checkpoint inhibitors (ICI) in a randomized Phase II trial, mRNA vaccines demonstrated improvement in recurrence free survival and distant metastasis free survival compared to ICI alone. We retrospectively examined patients (pts) with advanced melanoma treated more than 5 years ago on clinical trials with adjuvant NYESO1 or mRNA vaccine therapies (VT) then ICI upon recurrence and analyzed biomarkers correlating with treatment response. Methods: This retrospective study examined 22 pts with advanced melanoma treated between 2004-2017 with adjuvant vaccine therapies (VT). 10 of the 22 pts subsequently developed recurrent disease and were treated with ICI. We evaluated disease free interval following ICI, sex, age, BRAF status, HLA type, site of primary and metastatic disease, initial vaccine treatment, vaccine toxicities, stage and sites of melanoma recurrence, ICI treatment, response and toxicities, vaccine site flares or cutaneous immune related adverse events (irAEs) following ICI. Results: Of the 22 patients (11 male, 11 female) treated with adjuvant VT, median age at first vaccine was 53 years old. HLA type was known for 11 pts. Stage at initial VT was IIB to IIIC. 14 pts recurred following adjuvant VT. Median time from vaccine initiation to melanoma recurrence was 3.2 years (range 6.5 months to 11 years). 10 pts received ICI for recurrent melanoma, 3 pts received ipilimumab, 2 anti-PD1 monotherapy, 4 ipilimumab and nivolumab, and 1 nivolumab/relatlimab. Stage at first ICI was IIIB to IV M1d. 9 pts experienced cutaneous irAEs. 7 pts experienced local vaccine site flare reactions following ICI treatment. Additionally, 2 pts experienced vitiligo, 2 with dermatologic flares (bullous pemphigoid and psoriatic rash), 2 with generalized rash that resolved with steroid cream. 1 pt did not experience rash, vaccine site flare, nor irAE dermatologic flare. Of the pts who recurred, 2 pts had BRAF V600E mutations, and 1 of these pts experienced vaccine flare, the other did not. 1 pt with a BRAF Q16L mutation did not have vaccine flare. 6 out of 7 BRAF wild type pts who recurred and received ICI experienced a localized vaccine site flare. Median disease-free interval following ICI treatment was 1.5 years (range 3 months to 9 years). All 10 pts are disease-free and off ICI being closely monitored. Conclusions: Evidence of prior localized vaccination “flare” may be a biomarker for a complete immunologic response in pts with metastatic disease treated with immunotherapy. ICI targeting CTLA-4 and/or PD-1 both triggered this localized vaccination site response, suggesting that T cell memory and immunologic activation against melanoma antigens translate into clinical responses.