bluuebunny/crossref_metadata_2025 huggingface dataset:
Confirmed presence of the enigmatic ant Aphaenogaster gemella (Hymenoptera: Formicidae) in Iberia
Authors: Arcos Javier , Alarcón Paco
Published: July 2024

Background

While the Iberian Peninsula has been relatively well-studied from a myrmecological standpoint, the true presence of certain ant species has remained obscure for decades. In this context, the case of A. gemella (Roger, 1862) stands out as one of the most intriguing examples. Initially described from the Balearic Islands, this conspicuous species seemingly vanished from the archipelago by the 1980s, confining its current distribution to the Maghreb region. However, lingering doubt has persisted regarding its potential presence in Iberia, based on some old bibliographic records from Spain and Portugal.

Results

This study confirms the first known established population of A. gemella in the Iberian Peninsula (Tarifa, Southern Iberia). Two colonies were detected in an urban grass patch within the city center. The validity of other Iberian records regarding the species and its status as an exotic species are also discussed.

Conclusions

The presence of A. gemella in Southern Iberia highlights the need for targeted sampling efforts to delineate its actual range and distinguish it from morphologically similar species in the region.
Value of digital breast tomosynthesis in characterization of breast lesions in dense breast
Authors: Romeih Marwa , Raafat Tarek Ahmed , Ahmed Gehad , Shalaby Shymaa Abd El-Mawla , Ahmed Wafaa Ali Heidar
Published: July 2024

Background

Patients with dense breasts have a higher risk factor for developing breast cancer. Digital mammography (DM) exhibits a reduced sensitivity in dense breast tissue as a result of overlapping fibro-glandular tissue. Digital breast tomosynthesis (DBT) solves this problem, so allows better characterization of masses, asymmetries, and parenchymal distortion. It is useful in screening studies for early detection of breast lesions by accurate detection and description of their margins, shape, and extent as well as surrounding structures.

Objective

We aimed to evaluate the added value of DBT in characterizing of different breast lesions in dense breasts compared to DM.

Methods

A Prospective Cohort study involved ninety female cases having dense breast parenchyma (ACR C & ACR D) having breast complaint lesions detected by DM or ultrasound or recalled from screening units, during the period from June 2021 to Jan 2023.

All patient underwent DM and DBT with correlation with the pathological finding or follow up.

Results

As regards the characterization of breast mass DBT had higher sensitivity, higher specificity (98%, 87% respectively). However, DM showed less sensitivity, less specificity (58%, 80%,) with (p < 0.0001, p = 0.0005 respectively).

Conclusions

DBT effectively visualizes overlapping tissue in dense breasts. DBT is important due to its ability to detect breast cancer earlier, characterize lesions accurately, and inspect the margins of masses precisely, along with decreasing recall rates for false-positive results.
Phase 1/2 trial of the HPK1 inhibitor NDI-101150 as monotherapy and in combination with pembrolizumab: Clinical update.
Authors: Noel Marcus Smith , Demel Kurt C. , Srivastava Bhaskar , Daigle Scott R. , Boiko Scott , Hoerres Amanda , Basile Frank G. , Zhang Xinyan , Fraser Patricia , Dasen Sue , Chabas Daria , Gangolli Esha A. , Balaraman Rama , Sharma Sunil , Gutierrez Martin , Sommerhalder David
Published: July 2024

3083

Background: NDI-101150 is a potent, selective, oral inhibitor of hematopoietic progenitor kinase 1 (HPK1), with a different immunotherapy mechanism to other checkpoint inhibitors. NDI-101150 reactivates anti-tumor activity of T-cells, B-cells and dendritic cells (DCs), even under immunosuppressive conditions. Methods: Safety and preliminary efficacy (primary endpoints) of NDI-101150 alone (50–200 mg once-daily in 28-day cycles) and in combination with pembrolizumab are being assessed in patients (pts) with relapsed or metastatic solid tumors. NDI-101150 monotherapy expansion cohorts in renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC) and gastric/gastroesophageal (G/GEJ) cancer are also being assessed. Results: Dose escalation/expansion data as of Dec 13, 2023 are presented. Treatment (tx)-related adverse effects (TRAEs) in the safety set (N=39) for NDI-101150 monotherapy are presented in the table. 30 (76.9%) pts reported ≥1 TRAE and 5 (12.8%) pts reported grade ≥3 TRAEs. Most common TRAEs were nausea, vomiting, diarrhea and fatigue. Combination tx TRAEs (N=7) recapitulate the monotherapy profile (data not shown). NDI-101150 induced clinical benefit in 4/24 (16.7%) response-evaluable pts: complete response in 1 pt with clear cell RCC; stable disease (SD) ≥6 months in 3 pts (RCC [21 months], pancreatic cancer and endometrial cancer). Unconfirmed SD was noted in 2 pts with RCC, and in 1 pt each with NSCLC and G/GEJ cancer. Nearly dose-proportional increases in exposure were observed on Day 1 of Cycle 1 (C1) across 50–200 mg, with steady state achieved between Days 15 and 28 of tx. Pharmacokinetic profiles of monotherapy and combination tx cohorts were similar. Sustained inhibition of pSLP76 of >50% relative to pre-tx levels (predicted to achieve efficacy in nonclinical models) was observed at all doses tested by Day 15 of C1. Using a custom 12-plex immunofluorescence assay to monitor changes in the tumor immune microenvironment, an on-tx biopsy assessment from a pt with RCC showed increased infiltration of activated CD8+ T-cells and DCs compared to archival biopsy, aligning with the proposed mechanism of action. Conclusions: The observed clinical benefit and safety profile support continued evaluation of NDI-101150 as a viable next-generation immunotherapeutic. Clinical trial information: NCT05128487 . [Table: see text]
Association between PIK3CA mutations and disease-free survival in patients with HR+, HER2- tumors treated with adjuvant hormonal therapy: A real-world study in Croatia.
Authors: Čerina Dora , Dedic Plavetic Natalija , Belac Lovasić Ingrid , Separovic Robert , Flam Josipa , Pancirov Marija , Bajić Žarko , Tomic Snjezana , Vrdoljak Eduard
Published: July 2024

e12512

Background: Disease recurrence of early hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast tumor subtype is particularly challenging to manage due to its complex and very heterogeneous biological nature. Namely, due to primary and secondary resistance, one-quarter of patients with early disease will present with the disease recurrence. This variability in the timing of recurrence highlights the need to better identify key biomarkers that could predict therapeutic outcomes and guide personalized treatment strategies for these patients. Mutations in the phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene have a high prevalence of 30% to 40% in HR+/HER2- advanced breast cancer. They lead to activation of the PI3K/AKT/mTOR pathway, promoting cell growth, and proliferation, and are associated with poor prognosis in advanced breast cancer. Our aim was to examine this association and impact of PIK3CA mutation status on disease free survival (DFS) in HR+/ HER2- early breast cancer patients. Methods: We conducted a multicentric, retrospective cohort study in five Croatian institutions from July 2020 to December 2021. Study included initially early HR+/HER2- breast cancer patients who have been diagnosed with disease recurrence during adjuvant hormonal treatment or within first six years of follow up. The Cobas PIK3CA Mutation Testing Kit was used for real-time PCR-based amplification and mutation detection on the Cobas z 480 analyzer. We have analyzed differences in DFS from initiation of adjuvant endocrine therapy, using Cox, proportional hazard regression. Results: There was total of 186 patients, out of which 40.9% tested positive for the PIK3CA mutation. Primary and adjuvant treatment and in particular adjuvant endocrine treatment was similar between the two groups. After adjustment for 14 relevant covariates, we found that patients with positive PIK3CA status and with H1047 PIK3CA mutation had significantly lower hazard for disease recurrence in comparison to patients with no PIK3CA mutation (HR 0.65; 95% CI 0.45; 0.95; p = 0.024; HR 6.52; 95% CI 1.15; 36.95; p = 0.034 respectively; false discovery rate, FDR < 10%) and higher odds for late recurrence (p = 0.001, FDR < 5%). Conclusions: This study highlights the potential impact of PIK3CA mutations on disease recurrence during/following adjuvant endocrine treatment and by that potentially opens the door for further investigation of possibly more personalized treatment strategies.
A pilot study evaluating exercise intervention and body composition changes in patients with breast cancer and survivors.
Authors: Merifield Lindsey , Asato Chloe , Baron Kirsten , Toyama Matthew , Yamada Paulette , Teranishi-Hashimoto Cheri , Fukui Jami Aya
Published: July 2024

e12527

Background: In breast cancer patients and survivors, higher weight and adipose tissue levels have been associated with cardiovascular disease, diabetes, osteoporosis, and cancer recurrence. Additionally, various breast cancer treatments can increase body weight, adipose tissue, and inflammatory markers, raising multiple health concerns for breast cancer patients. Recent studies have found exercise programs alongside breast cancer treatment decreased adipose tissue; however, the weight loss and lifestyle results were not maintained following the exercise program. It remains unclear what strategies are effective in implementing long term lifestyle changes. Methods: In this pilot study, breast cancer patients and survivors (N=24, individual=12, group=12) followed an exercise program for 6 months, followed by 6 months of follow up. Participants ranged from ages 36 to75. Participants were randomized into group and individual exercise sections. Anthropometric measurements were taken at baseline, 3 months and 1 year. One-year measures were used to indicate continued lifestyle changes. Results: Significant differences in fat % body composition were found between baseline and 3 months in both group and individual with an average change of 1.12% (5.9% max) and 1.32% (5.4% max) respectively (P=0.0090). In addition, the baseline and 1-year average change of both group 2.8% (8.8% max) and individual 1.5% (9.6% max) sections was also seen and statistically significant (P=0.0040). Patients in individual and group exercise sections had up to 9.6% and 8.8% decrease in adipose tissue over 1 year, respectively.However, no significant difference was found between the individual and group exercise sections (P=0.3244). Conclusions: Patients from both the individual and group exercise sections continued to decrease adipose tissue composition throughout the 1-year study period, including after formal exercise course cessation at 6 months. This indicates that both group and individual exercise courses may offer similar health benefits to breast cancer survivors. We are continuing long term data collection to evaluate sustainability of the intervention benefits and to monitor breast cancer recurrence rates. Clinical trial information: NCT04013568 . [Table: see text]
Clinical factors associated with response to neoadjuvant chemotherapy in women of Hispanic origin diagnosed with early-stage TNBC or HER2+ breast cancer in the United States.
Authors: Herran Maria , Sabbagh Saad , Hijazi Ali , Mohanna Mohamed , Dominguez Barbara , Nahleh Zeina A.
Published: July 2024

e12535

Background: Neoadjuvant chemotherapy (NACT) has been strongly recommended for patients diagnosed with TNBC or HER2+ breast cancer. Hispanic populations are composed of a heterogenous group that include different racial and national backgrounds. This may account for differences in response to NACT. The aim of this study is to explore the factors associated with chemosensitivity among Hispanic women with early-stage TNBC or HER2+ breast cancer in the United States. Methods: This retrospective cohort study queried data from the National Cancer Database between 2010 and 2020 for women diagnosed with early-stage TNBC or HER2+ breast cancer who received NACT and identify as Hispanic (Mexican, Puerto Rican, Cuban, South or Central American and Dominican Republic). Patients were divided into two groups based on their response to NACT: sensitive (pTNM stage < cTNM, including ypT0N0) and refractory (pTNM stage ≥ cTNM stage). Using chi-square, socio-demographic and clinical factors associated with response to NACT were identified. Significant variables (p<0.05) were included in the multivariate logistic regression model predicting their response to NACT. Results: This study included N= 1,225 Hispanic women who met the inclusion criteria, 48.8% were Mexican, and 30.5% were from the Caribbean (Cuba, Puerto Rico, and Dominican Republic and 20.7% were from Central or South America). Within the overall group, n=769 (62.8%) were deemed sensitive to NACT, while n=456 (37.2%) were considered refractory. Significant variables associated with chemosensitivity at the multivariate level included age, tumor subtype, cN stage, and the use of multiagent NACT. Hispanic patients >70 years were less likely to respond to NACT (OR 0.57 95% CI 0.35-0.94, p-value=0.027). Meanwhile, patients diagnosed with TNBC were more likely to respond to NACT compared to HER2+ tumors (OR 2.0 95%CI 1.6-2.6, p-value<0.001). Patients with negative lymph nodes were 1.6 times more likely to have chemosensitive response compared to those with positive lymph nodes who tend to have more refractory disease (95%CI 1.6-2.6, p-value<0.001). Patients receiving single agent were 63% less likely to respond than multiagent NACT (95%CI 0.23-0.61, p-value<0.001). No major chemosensitive differences were found between individual Hispanic origin. Conclusions: In our nationwide Hispanic cohort, youngerage, TNBC, and cN0 were found to be significant predictors of neoadjuvant chemosensitive response in early-stage Breast Cancer. Further prospective inclusive studies are warranted to better delineate the heterogeneity in response to NACT among individual self-reported Hispanic ethnicities within the United States.
U.S. FDA analysis of enrollment of Asian patients from India in cancer clinical trials leading to approval from 2010 to 2022.
Authors: Srivastava Geetika , Leong Ruby , Nair Abhilasha , Kanapuru Bindu , Rizvi Fatima , Yang Felice , Lee Jennifer J. , Wedam Suparna B. , Dilawari Asma Ali , Fan Chaohong , Lee Sso , Andrada Frances , Lee Clara , Rivera Donna , Lemery Steven , Gao Jennifer , Kim Tamy , Pazdur Richard
Published: July 2024

e13779

Background: There are an estimated 4.4 million Indian Americans (Asian Indian), constituting 1.35% of the United States (US) population. Indian Americans enrolled in clinical trials are identified under the broad race category of Asian which includes Asians within the US and outside of US (Ex-US). Although cancer is the leading cause of death for Asians in US, they are under-represented in cancer clinical trials. Enrollment of Asian patients from India (API) in multiregional oncology clinical trials may provide important data regarding intrinsic and extrinsic factors impacting the etiology of cancer as well as response to anti-cancer treatment in Indian Americans. Common cancers reported amongst Asians in US are breast, prostate, colorectal, and lung, and in India are breast, head and neck, cervical and lung. Methods: We analyzed data from ~96,000 patients in 164 cancer therapeutic trials that led to an FDA approval for breast, prostate, colorectal, lung, liver, gastric, head and neck and cervical cancer indications from 2010-2022, and identified country for enrollments for all Asians. Results: Descriptive statistics of Asian patients enrolled within US, Ex-US and from India enrolled in breast, prostate, colorectal, lung, liver, gastric, head and neck, and cervical cancer trials that led to an FDA approval from 2010-2022 are summarized (Table). Enrollment of Asian patients within US was ≤1% (except liver and cervical cancer), from India was ≤2.1% of all Asians enrolled outside of US and ≤0.7% of all enrolled patients. Conclusions: It is difficult to accurately characterize the exact number of Indian Americans enrolled but are likely under-represented in cancer clinical trials leading to FDA approval.Sponsors should collect more granular information regarding enrollment of Asian patients in clinical trials. Enrollment of patients from India is extremely low relative to the population size. Efforts to increase enrollment of Indian Americans as well as patients from India in oncology clinical trials can bolster the evidence that supports FDA drug approval and its applicability to Indian Americans. [Table: see text]
PENTA as a model for advanced integrated cancer management in low-resource settings.
Authors: Pino Luis Eduardo , Franco Andrea Isabel
Published: July 2024

e13783

Background: Cancer models are reactive, fragmented, and volume-based care, in which the lack of coordination between different layers of care, along with clinical and quality variability, technological pressure, and dominant positions, result in high levels of inefficiency and waste, affecting economic sustainability and hence effective access. This is prohibitive for low-resource settings. Modern healthcare system models in this scenarios should focus on solve this problems. Comprehensive cancer management needs a reorientation towards value- and efficiency-generating architectures.Usual redesigns have focused on direct cost containment through intensified audits or new contracting and payment modalities between stakeholders. However, the real impact of these strategies is marginal, increasing sectoral mistrust and failing to meet the quintuple aim. PENTA is a comprehensive cancer management framework to optimize cancer patient care, with emphasis on clinical governance, data guidance, and clinical-administrative alignment. This is an operational model for stakeholders in low-resource settings. PENTA model has been successfully implemented in health insurance companies in Colombia and in private insurance branch in Peru. Methods: PENTA has been applied since 2020. We employed a work methodology based on the Agile-2 matrix, which allows for fluidity and lower resource consumption. This methodology is hybrid and its execution begins with an initial diagnosis of the process within the partner company. This diagnosis includes prioritizing interventions from each of the axes, but understanding that this is a systemic project that includes 5 fundamental axes. This axes must be worked on simultaneously and interdependently to achieve the greatest value. Axes are: 1. Smart Risk Management, 2. Advanced Clinical Gobernance, 3. Value Audit, 4. Technology Management and 5. Value-based Contracting Focus on managing inefficiencies and waste (optimization model), PENTA can generate early results across various dimensions such as clinical variability and technology costs. Structuring and using a cross-cutting data architecture is fundamental to the model's development into a data control tower. Results: Implementation of a data control tower for cancer cohorts , development of joint clinical pathways (insurer-payer) for prioritized diseases, clinical practice agreements with hierarchical positions on high-cost medications, implementation of mini health technology assessments (HTAs), and generation of new prospective payment modalities based on performance adjustment. The estimated savings generated are $1.5 million for the phase 2 in Colombia and $800,000 for the phase 1 in Peru. Conclusions: PENTA is an agile framework for cancer management that can be sucessfully adapted to low-resource settings.
A paradox of size: Case-volume, financial outcomes, and risk in the enhancing oncology model baseline period.
Authors: Indurlal Puneeth , Thomas Hope Ives , Altieri Jason , Garey Jody S. , Neeb Jessica , Staggs Stuart George , Wilfong Lalan S.
Published: July 2024

e13809

Background: The Centers for Medicare and Medicaid Innovation’s (CMMI) Enhancing Oncology Model (EOM) is a risk-bearing, population-based value-based care (VBC) model requiring participating physician group practices (PGP) to take financial risk and performance accountability for episodes of care for seven common cancers. We studied the association between case volume, financial outcomes, and risk in the EOM. Methods: Using deidentified public use EOM baseline episode files (2016 - 2020), and the EOM Price Prediction Model provided by CMMI, we calculated the predicted baseline price (BP) per episode and savings (difference between baseline price and actual expenditures (AE)), grouped PGPs per baseline period by episode count (case volume), and evaluated the risk (variation of savings). ANOVA, F-test, and pair-wise tests were used to evaluate statistical significance. Results: Two-thirds of the 16,348 PGP appearances per time-period (n) had <72 episodes (average: 93.8, median: 36). Table 1 shows population and savings metrics. There was a significant effect of episode counts on savings (ANOVA/F-test: F(5,16342) = 24.5, p<0.0005). Post hoc pair-wise t-tests (Holm correction to adjust p) indicated groups with <72 episodes had increased risk (4.5:1, p<0.0005) and >361 episodes had the least risk (p<0.0005). Groups with <72 episodes had four times the median savings than groups with >361 episodes. Conclusions: As expected with the law of large numbers, groups with fewer episodes are exposed to higher risk and extremes of financial outcomes in EOM-like models while paradoxically generating better savings. The impact of case-mix differences among groups is apt for further exploration. Differences in PGP dynamics and provider like-mindedness with care transformation is one possible explanation for this paradox. Future models should incorporate risk mitigating modeling techniques (case-volume adjustments) or facilitate easier partnering arrangements to engage groups with fewer episodes. [Table: see text]
Impact of gadopiclenol on decision making in patients with brain metastases: A post-hoc study.
Authors: Giordano Frank Anton , Fleckenstein Jens , Eckl Miriam , Stieler Florian , Bendszus Martin , Essig Marco , Wenz Frederik , Sarria Gustavo R.
Published: July 2024

e14003

Background: Gadopiclenol (Elucirem, Guerbet, France) is a new high relaxivity macrocyclic gadolinium-based contrast agent (GBCA), recently approved by the FDA and EMA at the dose of 0.05 mmol/kg. The aim of this post-hoc analysis was to evaluate the impact of contrast-enhanced MRI with gadopiclenol at 0.1 mmol/kg on decision making and radiotherapy (RT) treatment planning of brain metastases (BM). Methods: This is a post-hoc analysis of data from a phase IIb study where patients underwent two separate MRI examinations, one with gadopiclenol at 0.025, 0.05, 0.1 or 0.2 mmol/kg and one with gadobenate dimeglumine at 0.1 mmol/kg. MR images of patients who received both GBCAs at 0.1 mmol/kg, with ≥1 BM detected in either of the scans, were subjected to a blinded reader analysis and contouring by two radiation oncology experts. For each patient, treatment plans (stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]) were determined for both MRIs, with the gross target volume (GTV) indicating the contrast-enhancing aspects of the tumor. Mean GTVs and normal tissue volumes receiving 12 Gy (V12), as well as the Dice similarity coefficient (DSC) were obtained for the paired contours. The Spearman´s rank (ρ) correlation was additionally calculated. Furthermore, three experts blindly evaluated the contrast enhancement of each lesion for contouring purposes and subjectively qualified them as “better”, in detriment of the counterpart, or “equal”. Results: In total, images from 13 adult patients were analyzed. MRI with gadopiclenol depicted additional BM as compared with gadobenate dimeglumine in 7 patients (54%). The treatment plan was changed in 2 patients (15%), from no treatment to SRS and from SRS to WBRT. Gadopiclenol depicted additional BM in these 2 patients (from 0 and 10 BM with gadobenate dimeglumine to 1 and 15 BM with gadopiclenol). The mean GTVs and V12 were comparable between gadopiclenol and gadobenate dimeglumine (p=0.694, p=1.974). The mean DSC was 0.70 (SD: 0.14, ρ0.82). From a total of 36 answers, contrast enhancement was qualified as better with gadopiclenol in 21 (58.3%) evaluations, better with gadobenate dimeglumine in 8 (22.2%) evaluations, while no difference was observed in 7 (19.4%) evaluations. Conclusions: Gadopiclenol at 0.1 mmol/kg improved BM detection and contrast enhancement with potential impact on RT treatment decisions.
The clinical significance and expression of MAGE-A3 in patients with esophageal squamous cell carcinoma.
Authors: Wang Lan , Zuo Jing , Wang Yudong , Feng Li , Fan Zhisong , Wang Long , Han Jing , Zhang Xue , Liu Jiayin , Li Dan , Jin Hui
Published: July 2024

e16065

Background: More than half of esophageal cancer patients are diagnosed as advanced, and although immunotherapy has shown strong anti-tumor activity in esophageal cancer patients, the survival benefits are limited. Melanoma-associated antigen 3 (MAGE-A3) is a cancer testis antigen that is almost not expressed in normal tissues, but highly expressed in various malignant tumors, including esophageal cancer. MAGE-A3 has restrictive expression and good immunogenicity, making it an ideal immunotherapy target. This study aims to explore the expression and clinical significance of MAGE-A3 in esophageal squamous cell (ESCC) . Methods: 103 ESCC tissues and 77 adjacent cancerous tissues were collected, and the expression of MAGE-A3 was detected using immunohistochemistry. Furthermore, the relationship between MAGE-A3 and clinical pathological features was analyzed, and the prognostic significance of MAGE-A3 for ESCC patients was analyzed with overall survival (OS) as the endpoint. Results: The positive expression rate of MAGE-A3 in ESCC tissue was 68.0% (70/103), and the positive expression rate in adjacent tissues was 7.8% (6/77). The positive expression in ESCC was significantly higher than that in adjacent tissues. In ESCC, the expression of MAGE-A3 is associated with age, pathological grade, TNM staging, and lymph node metastasis. Both univariate and multivariate analyses showed that the expression of MAGE-A3 is an independent risk factor affecting the prognosis of ESCC patients. The high expression of MAGE-A3 predicted poor OS for ESCC patients. Conclusions: MAGE-A3 is highly expressed in ESCC and is associated with poor prognosis, and could be a potential prognostic marker and therapeutic target.
Sintilimab combined with definitive chemoradiotherapy in locally advanced esophageal squamous cell carcinoma: A single-arm, multicenter, phase 2 trial.
Authors: Lyu Jiahua , Li Tao , Liang Long , Li Churong , Jia Hongyuan , Qi Yunxiang , Zheng Xiumei , Fan Yu , Kuang Hao , Bai Hansong , Zhang Wanli , Lu Guangbing , Wang Gan
Published: July 2024

e16120

Background: Sintilimab is a PD-1 inhibitor that is approved for the treatment of advanced esophageal squamous cell carcinoma, but its efficacy and safety in locally advanced disease is unclear. We administered sintilimab with definitive chemoradiotherapy to patients with unresectable locally advanced oesophageal squamous cell carcinoma, and aimed to investigate the efficacy and safety of this treatment pattern. Methods: We conducted a multicenter, phase 2 trial at three cancer centers in sichuan province. Patients aged 18-75 years with untreated, unresectable, stage II-IVA esophageal squamous cell carcinoma, with an ECOG performance status of 0-2, and adequate organ and bone marrow function were eligible for inclusion. Patients received concurrent thoracic radiotherapy (60·0 Gy in 30 fractions), chemotherapy (two cycles of intravenous Albumin-Bound Paclitaxel [180 mg/m2, day1] and cisplatin [25 mg/m2, day1-3]), and Sintilimab (200 mg intravenously every 3 weeks for up to 1 year, or until disease progression or unacceptable toxicity). The primary endpoint was the progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate, quality of life (not reported here), and safety. The trial is registered with ClinicalTrials.gov, NCT046 02013. Enrolment is completed and follow-up is ongoing. Results: Between Oct 19, 2020, and Dec 08, 2023, 52 patients were enrolled. The median age was 65 years (IQR 58-71), 11 (21.1%) of 52 patients had stage IVA disease, and 49 (94.2%) patients were male and 3 (5.8%) were female. 50 (96.2%) of 52 patients patients completed the planned chemoradiotherapy. After a median follow-up of 15.0 months (IQR 7·9-28·0), the median PFS was not reached. The 1-, 2- and 3-year OS rates were 93.7%, 84.0% and 45.0%, respectively.The most common grade 3 or worse adverse event was neutropenia (23 [44.2%] of 52). Eight (15.4%) had treatment-related pneumonitis, but no patient died. Conclusions: Combining toripalimab with definitive chemoradiotherapy provided encouraging activity and acceptable toxicity in patients with locally advanced oesophageal squamous cell carcinoma, and this regimen warrants further investigation. Clinical trial information: NCT04602013 .
Analysis of ctDNA assay as a strategy for watchful waiting in locally advanced esophageal cancer.
Authors: To Hao Q. Q , Menon Harry , Green Garrett Barnard
Published: July 2024

e16126

Background: Standard treatment for locally advanced esophagogastric (EG) cancer is neoadjuvant chemoradiotherapy (CRT) followed by surgery. The treatment goal is curative in order to control the tumor in the thorax, prevent regional recurrence, and to help prevent or delay metastatic progression. Despite achieving pathologic complete response (pCR) after surgery, patients with supposed local control may have recurrence up to a third of the time. Circulating tumor DNA (ctDNA) is an evolving tool in the field of oncology used as an informative biomarker. We provide longitudinal, real world observation of ctDNA minimal residual disease (MRD) to predict pCR and risk of recurrence. Methods: 22 participants with newly diagnosed locoregional EG cancer were enrolled under single institution approved protocol [IRB#1864127-7]. CtDNA-based MRD levels were obtained by Natera SignateraTM bespoke mPCR-NGS assay. Additionally, Natera Altera TM was used as a non-invasive biopsy to provide the comprehensive tumor-specific genomic profile. We evaluated thirteen participants who underwent definitive surgery and those who did not. Non-invasive plasma samples were surveilled at various timepoints which included the time of diagnosis, during neoadjuvant CRT, after definitive surgery. The primary outcome is a comparison of assay recurrence (AR) to disease recurrence (DR) defined as radiologic or clinical disease recurrence in participants with locoregional disease. Exploratory endpoints examine the profile of tumor. Results: Baseline levels were detected (n = 22) at new diagnoses. Longitudinal results demonstrated ctDNA clearance in eight participants while undergoing neoadjuvant chemoradiaton. Residual ctDNA were found in five participants for which two had clinical disease recurrence. Esophagectomy was done in three participants achieving pCR. Post procedural ctDNA were detected in one participant. Conclusions: The clearance of ctDNA favors less clinical disease recurrence in this study. This may indicate that ctDNA clearance confers lower risk of relapase. However, a larger cohort prospective study will be needed to validate the application of ctDNA as an early biomarker. The future application of ctDNA can be used to identify patients who may benefit from a watchful waiting adjuvant strategy instead of proceeding with invasive esophagectomy.
Effects of Attractive Pickering emulsion gels loaded with oxaliplatin and lactate dehydrogenase inhibitors in hepatocellular carcinoma.
Authors: Ye Chanqi , Chen Ruyin , Li Qiong , Xu Shuaishuai , Ruan Jian
Published: July 2024

e16235

Background: Oxaliplatin (OXA) can be used as a palliative treatment for advanced hepatocellular carcinoma (HCC). While most patients still have rapid disease progression after OXA due to the drug resistance. The lactate dehydrogenase A (LDHA) inhibitors can reduce the inflammation-induced effects, metastasis, and proliferation potential of cancer cells. The combination of OXA and LDHA inhibitor may be an effective treatment for HCC. Methods: We adopt the water-in-oil attractive Pickering emulsion gel (APEG) to deliver OXA and LDHA inhibitor, GSK2837808A (GSK). OXA is dissolved in water and GSK is dissolved in iodized oil. We injected OXA+GSK@gel into the peritumoral tissues of subcutaneously tumorigenic HCC model mice, then observe the tumor size. Next, we apply immunohistochemical staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay on the dissected tumors to explore the cell proliferation and apoptosis. Meanwhile, flow analysis on the dissected tumors is applied to investigate the tumor immune microenvironment in HCC. Results: This drugs-loaded APEG has good biocompatibility and can release OXA and GSK slowly. OXA+GSK@gel has significant anti-tumor effect on HCC model, which can effectively inhibit tumor cell proliferation and promote tumor cell apoptosis. Meanwhile, flow analysis confirm that it could activate the tumor immune microenvironment in HCC. The infiltration of CD8+ T cells was increased, thereby providing better anti-tumor effect. Conclusions: The results suggest that the APEGs loaded with OXA and GSK can effectively improve the delivery efficiency and enhance the anti-tumor therapy.
Laparoscopic versus open hepatectomy for exophytic hepatocellular carcinoma: A multicenter propensity-matched comparative study.
Authors: Kongying Lin , Diao Yong-Kang , Huang Bin , Lv Guo-Yue , Wang Xian-Ming , Gu Wei-Min , Chen Zhong , Liang Ying-Jian , Jia Hang-Dong , Wang Hong , Chen Ting-Hao , Tang Shi-Chuan , Xu Jia-Hao , Wang Ming-Da , Shen Feng , Zeng Yong-Yi , Yang Tian
Published: July 2024

e16268

Background: As laparoscopic hepatectomy (LH) gains traction in the surgical management of hepatocellular carcinoma (HCC), its efficacy for exophytic HCC, a subtype with unique surgical challenges, remains under scrutiny. This study aims to compare the long-term outcomes of LH with traditional open hepatectomy (OH) in treating exophytic HCC. Methods: A multicenter retrospective analysis was conducted on patients with solitary exophytic HCC undergoing LH or OH at 10 hepatobiliary centers. Propensity score matching (PSM) and inverse probability treatment weighting (IPTW) were employed to balance the LH and OH groups for overall survival (OS) and recurrence-free survival (RFS) comparisons. Multivariable Cox-regression analysis determined the independent impact of surgical approach on OS and RFS. Results: The study included 270 patients, with 132 undergoing OH and 138 LH. Post-PSM, 97 matched pairs were analyzed. In this cohort, LH was associated with significantly lower 5-year OS (36.1% vs. 53.5%, P = 0.021) and RFS (31.7% vs. 44.9%, P = 0.013) compared to OH. Additionally, LH patients exhibited a higher rate of abdominal seeding metastases (19.6% vs. 8.2%, P = 0.023). Multivariable analysis in the PSM cohort revealed LH as an independent factor for reduced OS (HR, 1.62; 95% CI, 1.06-2.47; P = 0.025) and RFS (HR, 1.79; 95% CI, 1.22-2.64; P = 0.003), corroborated by IPTW cohort findings. Conclusions: This study indicates that LH may be less favorable than OH for exophytic HCC, potentially contraindicating its use in such cases. These findings highlight the necessity for further prospective research to refine surgical protocols for exophytic HCC.
Long-term follow-up of patients with hairy cell leukemia treated with different modalities at a single institution: Real-life experience over 25 years.
Authors: Khan Muneer , Meseeha Marcelle , Richards Julie L. , Poulose Joyson , Talamo Giampaolo
Published: July 2024

e19023

Background: Hairy cell leukemia (HCL) is an uncommon and indolent leukemia of mature B cells, accounting for 2% of all lymphoid neoplasms. We analyzed characteristics, treatment modalities, response rates, and survival of HCL patients followed at our institution. Methods: We retrospectively reviewed data from the medical records of 56 consecutive HCL patients evaluated in our Hematology/Oncology clinic between 1998 and 2023. Results: The median age at diagnosis was 59 years (range, 37-94). Forty-nine patients (87%) were male. First-line therapy was cladribine in 30 patients (54%), cladribine + rituximab in 6 patients (11%), observation in 5 patients (9%), and another modality (fludarabine, pentostatin, single agent-rituximab, and other) in the rest of patients. The median follow-up was 122 months (1-291). The overall response rate was 96%. CR and PR rates were 68% and 28%, respectively. Relapses were observed in 44% of patients. The median OS was not reached, and the median PFS was 181 months (95% CI, 128-252). The 5-year and 10-year PFS were 78% and 29%, respectively. Only 3 patients (5%) died as a result of HCL, either indirectly from immune suppression (pneumonia, 2 patients) or directly (cachexia in 1 patient, untreated because of advanced age and comorbidities). Conclusions: Treatment with purine analogues such as cladribine, plus or minus rituximab, achieves deep and durable responses in most HCL patients. Although relapses were commonly observed, the vast majority of HCL patients did not die as a result of HLC.
Real-world understanding of the unmet need for treatment of non-covalent BTKi in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).
Authors: Choksi Rushir J. , Hou Jing-Zhou , Li John , Gart Mike , Vasudevan Anupama , Blanc Simon
Published: July 2024

e19028

Background: Non-covalent (nc) Bruton Tyrosine Kinase inhibitors (BTKi) for the treatment of Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (CLL/SLL) provide patients with a new treatment option after resistance to on-target BTK mutations or PLCγ2 mutations that bypass BTK inhibition. Given the December 1, 2023 accelerated FDA approval for pirtobrutinib, a nc-BTKi, in the treatment of CLL/SLL for treatment of patients who have received at least two prior lines of therapy with a covalent (c) BTKi and a B-Cell Lymphoma 2 Protein Inhibitor (BCL2i), we sought to understand the addressable population for treatment with nc-BTKI therapy in a real-world database of CLL/SLL patients. Methods: We used the Integra Connect PrecisionQ real-world de-identified database of over 3 million cancer pts across 500 sites of care to identify CLL/SLL pts for the analysis. The CLL patients included for the analysis were on a treatment in 2023 and must have had either >5 CLL/SLL diagnosed visits or more CLL/SLL visits than non-CLL/SLL visits if <5 CLL/SLL diagnosed visits. Descriptive analyses were used for this study. Results: Of the 6,992 patients treated for CLL/SLL in 2023, the median age at treatment start was 71, 62% were male, 65% identified as White, 6% as African American, and 29% as Other. Of the pts, 12% received a c-BTKi and BCL2i, 64% received a c-BTKi only, and 12% received a BCL2i only. Of the 12% of pts who received a c-BTKi and BCL2i, 191 pts started a subsequent line of therapy. Among pts who received a c-BTKi and BCL2i, 79% received a BTKi therapy first, 10% received a BCL2i therapy first, and 12% had a line of therapy with both a BTKi and BCL2i. We found 59 pts who received nc-BTKi; among those pts, 51% received a c-BTKi and BCL2i prior to initiation of nc-BTKi. The median age at first treatment for CLL/SLL was 71.7 for those who received a c-BTKi, 71.1 for those who received a BCL2i, and 70.8 for those who received nc-BTKi. The median age at first diagnosis for CLL/SLL was 68 for those who received a c-BTKi, 66 for those who received a BCL2i, and 63 for those who received nc-BTKi. The median time to first treatment was 470 days for pts treated with a c-BTKi, 507 days for pts treated with BCL2i, and 587 days for pts treated with nc-BTKi. Conclusions: We found that among nearly 7,000 treated patients in the database, 12% were treated with both a c-BTKi and BCL2i; of those, just 23% started a subsequent treatment. Among patients who were treated with a nc-BTKi we found their median age at treatment start and diagnosis was lower than those who received a c-BTKi or BCL2i respectively.
Hodgkin’s lymphoma, lymphocyte-depleted, reticular: An NCDB analysis of demographic and socioeconomic factors of diagnosed patients.
Authors: Nowlen Frances , Chin Kat , Jung Huang Po , Halloum Anas , Silberstein Peter T. , Heise Craig , Hsia Beau
Published: July 2024

e19033

Background: Lymphocyte-depleted Hodgkin's lymphoma (LDHL) is an aggressive, rare form of Hodgkin’s lymphoma (HL). The LDHL reticular subtype (LDHL-R) is characterized by a scant invasion of lymphocytes without an increase in collagen fibers by fibroblasts. Patient demographics and clinical features of LDHL-R are poorly understood, causing it to frequently be misdiagnosed as other variants of HL. At diagnosis, patients have often already progressed to late disease staging. The demographic and socioeconomic factors of patients diagnosed with LDHL-R within the National Cancer Database (NCDB) were analyzed to better understand its epidemiology. Methods: A retrospective cohort analysis was performed using data from the 2004-2020 NCDB of the 51 cases of LDHL-R (ICD-O-3 9655). Demographic and socioeconomic factors such as age, sex, race, Hispanic status, treatment facility type, Charles-Deyo score, and 90-day mortality were examined using descriptive statistics. Diagnostic trends were quantified through regression analysis. Results: A total of 51 patients were diagnosed with Hodgkin lymphoma, lymphocyte depletion, reticular subtype within the NCDB. The most common primary site of diagnosis was within lymph nodes of multiple regions (41%). The majority of patients were males (65%), White (72%), and non-Hispanic (74%). Patients tended to have residence in metropolitan counties with populations greater than 1 million (71%) and were enrolled in academic/research programs (36%). Most of the patients were privately insured (41%) followed by those insured by Medicare (29%). A higher percentage of patients were in the top quartile of income earners (31%) than those in the second, third, or fourth quartiles. The incidence rate of diagnosis remained constant from 2004 to 2020 (R² = 0.02). The mean age of diagnosis was 51 years (SD=21, Range=14–90). Using the AJCC System, patients tended to be classified as Stage IV (41%) at diagnosis and had a Charlson-Deyo comorbidity score of 0 (71%). Primary treatment methods involved chemotherapy (84%) and radiation therapy (20%). Surgical intervention was given to 14 patients, and post-surgery survival rates were 93% after 90 days. Conclusions: To the best of our knowledge, this is the first NCDB analysis of the demographic factors of patients diagnosed with LDHL-R. Consistent with previous studies about the aggressiveness of this subtype of Hodgkin’s Lymphoma, most patients received a Stage IV diagnosis. Understanding LDHL-R’s epidemiology could result in significantly earlier diagnoses and improved prognosis. Patients tended to be male, White, and non-Hispanic with a residence in metropolitan counties. To improve understanding of the impact of demographic and socioeconomic factors of the diagnosis, treatment, and survival of patients with LDHL-R, more research is recommended.
Associations of early adverse events with clinical outcomes in patients with NSCLC treated with EGFR tyrosine kinase inhibitors.
Authors: Lin Fang-Ju , Lin Wen-Yen , Wang Chi-Chuan , Shih Jin-Yuan
Published: July 2024

e20551

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) constitute the primary treatment modality for EGFR-mutant non-small cell lung cancer (NSCLC). While efficacious, EGFR TKIs are associated with adverse events (AEs) like dermatologic toxicities, diarrhea, and stomatitis. This study examined the prognostic implications of these on-target AEs in NSCLC patients receiving EGFR TKI therapy. Methods: A retrospective cohort study was conducted, encompassing advanced NSCLC patients treated with first-line EGFR TKIs within two distinct healthcare delivery systems in Taiwan between June 2011 and December 2019. Patients were stratified by TKI type, and those who had received AE reliever medications within 180 days prior to EGFR TKI initiation were excluded. We examined correlations between AEs and key endpoints: time to next treatment (TTNT) and overall survival (OS). To minimize immortal time bias, a landmark analysis at 60 days post-treatment initiation was utilized. On-target AEs were identified based on the issuance of at least two prescriptions for AE management on different dates within this period. Multivariable Cox proportional hazards models were utilized to evaluate the association between AEs and clinical endpoints, and a random-effects meta-analysis was performed to combine findings from both institutions. Results: Our analysis included 1,605 patients on gefitinib, 848 on erlotinib, and 1,236 on afatinib. Despite potential variations in AE reporting due to prescribing behaviors, the incidence of AE within the first 60 days of treatment was highest for afatinib, particularly with diarrhea (76.7%) and stomatitis (14.9%), followed by erlotinib with notable skin reactions (49.4%). Gefitinib showed the lowest incidence rates across all examined AEs. Of note, afatinib-treated patients who experienced diarrhea within the initial 60 days demonstrated a statistically significant extension in OS (HR 0.75, 95% CI 0.60-0.92). No significant prognostic link was found for other AEs in afatinib users or any AEs among users of gefitinib and erlotinib. Sensitivity analyses, incorporating modified AE definitions, corroborated these outcomes. Conclusions: Identifying AEs via prescription records for symptom relief poses methodological challenges and introduces uncertainty. Nevertheless, the occurrence of diarrhea within the first 60 days of therapy emerged as a significant predictor of enhanced OS in EGFR-mutant NSCLC patients receiving afatinib. This finding suggests a potential prognostic implication. The correlation was not evident in patients treated with first-line gefitinib or erlotinib.