bluuebunny/crossref_metadata_2025 huggingface dataset:
The adoption of international travel measures during the first year of the COVID-19 pandemic: a descriptive analysis
Authors: Grépin Karen A. , Song Mingqi , Piper Julianne , Worsnop Catherine Z. , Lee Kelley
Published: October 2024

Objective

To describe the adoption of international travel measures during the first year of the COVID-19 pandemic.

Methods

To comprehensively analyze the measures adopted, we constructed a dataset based on the WHO’s Public Health and Social Measures (PHSM) database, which covered 252 countries, territories, or other areas (CTAs), including all 194 WHO Member States, from December 31, 2019, to December 31, 2020. We examined the adoption of measures by type, over time, and by the implementing and targeted CTA, including their levels of income.

Findings

We identified 11,431 international travel measures implemented during the first year of the pandemic. The adoption of measures was rapid and widespread: over 60% of Member States had adopted a travel measure before the WHO declared COVID-19 a Public Health Emergency of International Concern on January 30, 2020. Initially, health screening and travel restrictions were the most adopted measures; however, quarantine and testing became more widely adopted over time. Although only a small portion of the total measures adopted constituted full border closure, approximately half of all Member States implemented this measure. Many travel measures targeted all CTAs but were unlikely to have been adopted universally enough to provide public health benefits. Low-income countries relied more on more universal measures, including full border closure, and were slower in scaling up testing compared to higher-income countries.

Conclusion

The adoption of international travel measures during the first year of the COVID-19 pandemic varied across jurisdictions and over time. Lower-income countries used a different mix and scaled-up measures slower than higher-income countries. Understanding what measures were used is crucial for assessing their effectiveness in controlling the spread of COVID-19, reviewing the usefulness of the International Health Regulations, and informing future pandemic preparedness and response activities.
Impact of rapid response system in mortality and complications post-orthopedic surgery: a retrospective cohort study
Authors: Choi Hey-ran , Song In-Ae , Oh Tak Kyu
Published: October 2024

Background

Rapid response systems (RRSs) are used in hospitals to identify and treat deteriorating patients. However, RRS implementation and outcomes in orthopedic and surgical patients remain controversial. We aimed to investigate whether the RRS affects mortality and complications after orthopedic surgery.

Methods

The National Health Insurance Service of South Korea provided the data for this population-based cohort study. Individuals who were admitted to the hospital that implemented RRS were categorized into the RRS group and those admitted to a hospital that did not implement the RRS were categorized into the non-RRS group. In-hospital mortality and postoperative complications were the endpoints.

Results

A total of 931,774 adult patients were included. Among them, 93,293 patients underwent orthopedic surgery in a hospital that implemented RRS and were assigned to the RRS group, whereas 838,481 patients were assigned to the non-RRS group. In multivariable logistic regression analysis, the RRS group was not associated with in-hospital mortality after orthopedic surgery compared with the non-RRS group (odds ratio [OR] 0.93, 95% confidence interval [CI] 0.80, 1.08; P = 0.350). However, the RRS group was associated with a 14% lower postoperative complication rate after orthopedic surgery than the non-RRS group (OR 0.86, 95% CI 0.84, 0.86; P < 0.001).

Conclusions

The RRS was not associated with in-hospital mortality following orthopedic surgery in South Korea. However, RRS deployment was related to a decreased risk of postoperative complications in patients undergoing orthopedic surgery.
Primary ileal myeloid sarcoma presenting with bowel obstruction: a case report
Authors: Minagi Hitoshi , Kanaya Nobuhiko , Kondo Yoshitaka , Kakiuchi Yoshihiko , Kuroda Shinji , Shoji Ryohei , Kashima Hajime , Matsumi Yuki , Kikuchi Satoru , Shigeyasu Kunitoshi , Teraishi Fuminori , Kagawa Shunsuke , Fujiwara Toshiyoshi
Published: October 2024

Background

Myeloid sarcoma (MS) is an extramedullary tumor constituted by myeloid blasts or immature myeloid cells. It frequently occurs in conjunction with acute myeloid leukemia (AML); however, it can exceptionally manifest in patients without leukemia. Here, we present a rare case of primary MS originating in the small bowel without evidence of bone marrow involvement.

Case representation

A 33 year-old female with no relevant medical history was admitted to our hospital with recurrent abdominal pain. Computed tomography (CT) revealed bowel obstruction due to thickening of the ileum wall, which was suspected to be an ileal tumor. Initially, ectopic endometriosis was suspected because of abdominal pain associated with the menstrual cycle and changes observed on a follow-up CT scan. The lesion could not be detected by double-balloon endoscopy. Despite conservative treatment, the obstruction persisted, and laparoscopic partial ileal resection was performed, which revealed extensive involvement of the ileum and mesentery. Additionally, the mesentery of the resected ileum was extremely thickened. Histopathological and immunohistochemical examinations of the surgical specimen indicated ileal MS. Bone marrow aspiration after discharge was negative for cytological findings of leukemia, leading to a final diagnosis of primary ileal MS. Her postoperative course was uneventful, and she is currently undergoing systemic chemotherapy tailored to AML at another hospital.

Conclusions

Even though MS of the small bowel is rare and may not be considered preoperatively, similar surgical treatment to that of other small bowel malignancies can ensure proper postoperative diagnosis and appropriate chemotherapy. Given the potential need for chemotherapy, ensuring surgical safety that allows for its rapid initiation is critical.
Dexrazoxane prevents vascular toxicity in doxorubicin-treated mice
Authors: Krüger Dustin N. , Bosman Matthias , Van Craenenbroeck Emeline M. , De Meyer Guido R. Y. , Franssen Constantijn , Guns Pieter-Jan
Published: October 2024

Background

Doxorubicin (DOX) is used for breast cancer and lymphoma, but can cause cardiotoxicity, arterial stiffness, and endothelial dysfunction. We recently reported SERPINA3N as biomarker of cardiovascular toxicity in patients and mice. Dexrazoxane (DEXRA) is an FDA-approved drug that prevents DOX-induced cardiac toxicity in high-risk patients. However, the effect of DEXRA on vascular dysfunction during DOX treatment has not been documented. Therefore, here we investigated whether DEXRA protects against DOX-induced arterial stiffness, endothelial dysfunction, and SERPINA3N upregulation in tissue and plasma from mice.

Methods

Male C57BL6/J mice were treated with DOX (4 mg/kg), DEXRA (40 mg/kg), a combination (DEXRA + DOX), or VEHICLE (0.9% NaCl) weekly i.p. for 6 weeks (n = 8 per group). Cardiovascular function was measured in vivo by ultrasound imaging at baseline, weeks 2 and 6. Vascular reactivity was analyzed ex vivo in the thoracic aorta at week 6 and molecular analysis was performed.

Results

DEXRA prevented left ventricular ejection fraction decline by DOX (DEXRA + DOX: 62 ± 2% vs DOX: 51 ± 2%). Moreover, DEXRA prevented the increase in pulse wave velocity by DOX (DEXRA + DOX: 2.1 ± 0.2 m/s vs DOX: 4.5 ± 0.3 m/s) and preserved endothelium-dependent relaxation (DEXRA + DOX: 82 ± 3% vs DOX: 62 ± 3%). In contrast to DOX-treated mice, SERPINA3N did not increase in the DEXRA + DOX group.

Conclusion

Our results not only confirm the cardioprotective effects of DEXRA against DOX-induced cardiotoxicity but also add preservation of vascular endothelial cell function as an important mechanism. Moreover, the study demonstrates the potential of SERPINA3N as a biomarker for monitoring cardiovascular complications of DOX in high-risk patients.
The status of dialysis patients in Asian countries under COVID-19 disaster as of December 2019–June 2022: Vietnam, Indonesia, and Mongolia
Authors: Hyodo Toru , Hirawa Nobuhito , Kuragano Takahiro , Takemoto Yoshiaki , Pham Bui Van , Nguyen Ha Minh , Nguyen Loc Duc , Vu Hoa , Le Giang , Nguyen Hang , Nguyen Tung , Phan An , Widiana I. Gde Raka , Adiya Saruultuvshin , Nergui Mandkhai , Dashmend Galmunkh , Bayankhuu Narantungalag , Dorjsuren Tsatsral , Ulziibayar Dolzodmaa , Zulpihar Nurguli , Batbold Bolorchimeg , Bat-Ochir Amartuvshin , Dorj Chuluuntsetseg
Published: October 2024

On 1 December 2019, an outbreak of coronavirus disease 2019 (COVID-19) occurred in Wuhan, China, and quickly spread around the world. In an effort to prevent transmission, global traffic flows were affected and lectures by international speakers at the 2022 Annual Meeting of the Japanese Society for Dialysis Therapy were streamed over the internet. Speakers from Vietnam, Indonesia, and Mongolia reported on the status of COVID-19 infection in dialysis patients from December 2019 to June 2022. In addition, the situation in Japan is discussed in the introduction. In Japan, the mortality rate due to COVID-19 infection in dialysis patients was approximately 20% in a national statistical survey before the introduction of the vaccine, and decreased to 3.1% with the introduction of the vaccine. In Vietnam, the mortality rate was 42% in non-vaccinated recipients and 21% in two-dose recipients, but this was reported by a single center. Mortality among dialysis patients with COVID-19 infection in Indonesia was 57%, although reported by a single center. In Indonesia, 6 million people were infected with COVID-19, and the number of COVID-19 cases among dialysis patients was estimated to be around 52,200. Mongolia was considered to be the country that was able to move to vaccination while most effectively controlling the domestic spread of severe acute respiratory syndrome coronavirus 2 compared with many other countries.
Gender differences in cardiac rehabilitation participation and outcomes: an 18-year retrospective study in Iran
Authors: Najafi Marzieh , Teimouri-Jervekani Zahra , Jamalian Marjan , Roohafza Hamidreza , Paknahad Mohammad Hossein , Hadavi Mohammad mahdi , Dorostkar Neda , Sadeghi Masoumeh
Published: October 2024

Background

Cardiac rehabilitation (CR) is crucial for addressing cardiovascular diseases globally, with a specific emphasis on gender differences. Despite its demonstrated benefits for women, there's limited acceptance globally, especially in low- and middle-income countries. The program aims to optimize risk factors and improve overall patient well-being.

Methods

A cohort study was performed on those who were candidates for CR programs during 2001–2019. Assessments were performed within one week before and one week after the 8-week CR program. Age, sex, smoking status, clinical data, resting systolic and diastolic blood pressure (SBP and DBP, respectively), echocardiography and laboratory data were obtained. Functional capacity was evaluated using the international physical activity questionnaire, and a treadmill exercise test. Anxiety, depression, general quality of life (QoL), and health-related QoL were selected for psychological status. Then statistical analysis was performed on data.

Result

In this study, the number of male patients was 1526 (73.69%). The average age of patients in the female group was higher than that of males (58.66 ± 9.08 vs. 56.18 ± 9.94), according to the crude model results, the changes in emotional, social and physical scores were significant (P-value:0.028, 0.018, 0.030), as well as the differences in Mets and smoking were significant (P-value for both < 0.001) in the adjusted model, the emotional variables and Mets changes were significant in two groups, so that the emotional score in the female group was higher than that of the male group, and the female Mets score was significantly lower than that of the male group.

Conclusion

The CR program can improve cardiovascular outcomes, but the greatest impact was on the quality of life, patient METs and smoking behavers. Also the number of female participants in the CR program was less than the number of males.
Hemophagocytic lymphohistiocytosis: pediatric hepatic perspective
Authors: El-Sayed Manal Hamdy , Abd El Kader Salwa Mostafa , Ebeid Fatma Soliman Elsayed , El-Shorbagy Fatma Mohamed , Ragab Iman Ahmed
Published: October 2024

Background

Hepatic manifestations of hemophagocytic lymphohistiocytosis (HLH), an underrecognized primary presentation in pediatric age group, mandate high levels of suspicion for early diagnosis.

Aim

This is to study the frequencies of clinical and laboratory hepatic involvement in patients with familial/primary or secondary/acquired HLH in relation to disease reactivation and outcome.

Methods

A 6-month retrospective cohort study recruited 35 patients with HLH. Detailed clinical, laboratory, and genetic characteristics of HLH were collected. Hepatic transaminases and synthetic liver functions were collected at presentation, weeks 2 and 8 after starting treatment, and at time of reactivation. Biochemical liver involvement was considered when alanine aminotransferase (ALT) lived three-times more than the upper normal level. Overall (OS) and reactivation free survival were analyzed according to liver involvement.

Results

Twenty patients (57%) had genetically confirmed HLH, 12 (34.3%) had MUNC13D mutations, 3 (8.5%) had STXBP2 mutations, and 5 (14.3%) had RAB27A mutations, while 9 (25.7%) had no genetic mutations with 4 of them had secondary HLH. Six patients (17.2%) patients had unknown genetics status. Median (IQR) age of the whole group was 18 months (6–36) with an age range of 2–108 months. Liver enlargement was detected at diagnosis in 29 (82.9%) and at reactivation in 18 (51.4%) patients. Eight (22.86%) patients had biochemical hepatic involvement at presentation with no significant difference in their demographic, initial clinical presentation, survival, or the type of mutant gene according to liver involvement.

Conclusion

Variable hepatic biochemical involvement might be the presenting manifestation of HLH at diagnosis and upon reactivation, yet it did not impact disease outcome.
Study of blood eosinophils and plasma periostin as biomarkers for response of COPD patients to ICS/LABA treatment
Authors: Abdulsattar Sara Abdulbadie , Hantera Mohamed Sayed , Hodeb Hossam Abdel Mohsen , Kholy Amira Abdelgalil El , Kholy Gamal Amer El
Published: October 2024

Background

Eosinophilic airway inflammation has been detected in up to 40% of chronic obstructive pulmonary disease (COPD) patients during stable periods of the disease, and increased sputum eosinophil count was associated with better lung function, more future exacerbations, and symptoms that responded better to treatment with inhaled and oral corticosteroids.

The aim of this work was to investigate the relationship of blood eosinophils and plasma periostin with lung function changes related to ICS and long-acting beta2-agonist combination treatment in stable COPD patients for 3 months.

Methods

This prospective experimental study was carried out on 50 COPD patients with post-bronchodilator FEV1/FVC ratio < 70%. Patients collected from outpatient clinics of Chest Department Tanta University Hospitals, Tanta Chest Hospital, and Mansoura Chest Hospital from February 2020 to February 2022. Patients were subjected to complete history taking, and clinical examinations including general and local examinations and laboratory investigations (complete blood count to assess eosinophilic count, arterial blood gases, and plasma periostin) and spirometry were done for all patients pre- and post-treatment. All patients received 3 months of treatment with a fixed dose of combined inhalers of ICS and LABA, and then they were classified into FEV1 responder and FEV1 non-responder according to improvement in FEV1 at least 12% and 200 mL from baseline of 3 months of combined treatment with ICS/LABA.

Results

Blood eosinophil count had a significant positive correlation with smoking index (pack/year), negative correlations with FEV1% of predicted, FEV1 actual value (L), and FEV1/FVC ratio. Plasma periostin concentration had significant positive correlation with blood eosinophil count, COPD grade, and FVC actual value (L) and significant negative correlations with FEV1% of predicted, FEV1 actual value (L), and FEV1/FVC. Cutoff values of blood eosinophil count > 265 cell/µL, plasma periostin concentration > 15.747 ng/mL, and FEV1% < 40.5% were associated with posttreatment FEV1 response.

Conclusions

COPD patients with poor lung functions regarding FEV1/FVC ratio, FEV1 actual value (L), and FEV1% of predicted as well as high blood eosinophil count and high plasma periostin concentration are predicted to have FEV1 response with fixed-dose ICS/LABA combination treatment.
Patients with early-onset metastatic colorectal cancer as an emerging distinctive clinical and molecular phenomenon.
Authors: Pretta Andrea , Ziranu Pina , Perissinotto Eleonora , Ghelardi Filippo , Marmorino Federica , Giampieri Riccardo , De Grandis Maria Caterina , Ciracì Paolo , Puzzoni Marco , Cerma Krisida , Sciortino Carolina , Taravella Ada , Pusceddu Valeria , Damonte Camilla , Berardi Rossana , Lonardi Sara , Bergamo Francesca , Pietrantonio Filippo , Cremolini Chiara , Scartozzi Mario
Published: October 2024

3531

Background:
Despite a reduction of both incidence and mortality from CRC in the elderly population, several studies published in the last decade have shown an increase in the incidence of early-onset CRC (EO-CRC), conventionally defined as cancer that occurs in adults between the ages of 18 and 49. Clinical and prognostic data on this setting are limited and conflicting. The aim of our study was to evaluate the clinical, prognostic, and molecular profiles of metastatic EO-CRC patients (age at diagnosis ≤ 50) in order to identify potentially relevant differences compared to a control group late-onset CRC (LO-CRC).
Methods:
We retrospectively collected data from 1272 metastatic colorectal cancers from 5 different Italian Institutions: 693 (54.5%) EO-CRC and 579 (45.5%) LO-CRC as control group. All patients had one or more metastatic sites, molecular profiling available (including RAS, BRAF, and MSI status), and underwent at least one line of treatment for metastatic disease. The main objective of the study was to the evaluate clinical outcome for the global population of EO-CRC patients in different clinical and molecular subgroups according to RAS and BRAF status and in comparison to patients included in the control group.
Results:
In the EO-CRC group median age was 42.8 (20.0-50.9) and 66.7 (51.0-86.2) in the control group. M/F ratios were 1:1 and 2:1, respectively. In the overall population, mOS was 34,7 in EO-CRC pts vs 43,0 months (mo) (
p < 0,0001
) in the control group. In the RAS/BRAF mutated subgroup mOS in EO-CRC pts was 30,3 vs 34,0 mo in the control group (
p = 0,0156
). In RAS/BRAF wild-type subgroup mOS in EO-CRC pts was 43,0 vs 50,0 mo (
p = 0,0290
). Finally, in the BRAF V600E mutated subgroup EO-CRC pts showed a 16 mo mOS vs 26 mo (
p = 0,04
). In the overall population, mPFS was 11,0 in EO-CRC pts vs 14,0 mo (
p < 0,0001
) in the control group. Furthermore, the overall response rate (ORR) was 63% in EO-CRC and 67% in LO-CRC.
Conclusions:
Findings from a large population of EO-CRC patients indicate a general worse prognosis for patients with early-onset colorectal cancer compared to late-onset patients. Interestingly this seems to occur regardless of the molecular status. These observations might have a considerable impact on clinical practice and research. Subsequent investigations will be needed to further understand the specific clinical and molecular characteristics of this growing group of patients to better define the more appropriate treatment strategy.
Neoadjuvant chemotherapy with FOLFOXIRI plus lateral lymph nodes dissection for the treatment of resectable rectal cancer with lateral lymph node metastasis: A single-arm, investigator-initiated, phase II trial.
Authors: Sun Yongkun , Jiang Yujuan , Zhou Haitao , Pei Wei , Jiang Zheng , Tang Jianqiang , Song Yan , Zhao Zhixun , Quan Jichuan , Zhang Mingguang , Hu Xiyue , CHEN BO , Su Aijiang , Tang Yuan , Li Erni , Liu Qian , Jiang Jun , Liang Jianwei , Wang Xishan
Published: October 2024

3533

Background:
There is a lack of standardization in the comprehensive treatment strategies for rectal cancer with lateral lymph node metastasis (LLNM), which results in an unfavorable oncological outcome. We conducted the present phase II trial by performing neoadjuvant chemotherapy with 5-fluorouracil, irinotecan, and oxaliplatin (FOLFOXIRI) regimen plus lateral lymph node dissection (LLND) for resectable rectal cancer with LLNM to decrease the lateral recurrence and distant metastasis rates.
Methods:
This prospective, single-arm phase II trial was conducted from April 2018 to February 2023, and included patients with cT3-4aN+M0 resectable rectal cancer and clinical suspicion of LLNM based on preoperative MRI. Patients were treated with three cycles of FOLFOXIRI, and those with evidence of treatment response continued to receive two cycles of FOLFOXIRI. Total mesorectal excision plus LLND was performed at 3-4 weeks after completing the last cycle of preoperative chemotherapy, followed by 3 cycles of XELOX.
Results:
A total of 58 patients engaged in this research, and 53 were finally enrolled. The pathological examination detected microscopic LLNM in 12 (22.6%) patients. The pathologic complete response (pCR) rate was 11.3% (6/53), and the downstaging (ypstage 0 to 1) rate was 30.2% (16/53). DFS events were observed in 7 patients, and OS events were reported in 2 patients after a median follow-up of 30 months. The 3-year DFS rate was 88.3%, the 3-year local recurrence-free survival rate was 94.7%, and the 3-year OS rate was 91.3%. There were 14 (26.4%) cases with six grade 3/4 adverse events.
Conclusions:
Neoadjuvant chemotherapy with the FOLFOXIRI regimen plus LLND can significantly reduce the risk of local recurrence and distant metastasis in resectable rectal cancer with LLNM, which may be a new treatment option.
Clinical trial information: NCT04850027
.

Variable, n (%)
Total

pCR (ypT0N0), n (%)
6 (11.3%)

Total LNs harvested

Median (IQR)
30 (24~40)

LLNs harvested

Median (IQR)
12 (8~17)

Pathological T category

ypTis
1 (1.9%)

ypT0
6 (11.3%)

ypT1
2 (3.8%)

ypT2
11 (20.8%)

ypT3
31 (58.5%)

ypT4
2 (3.8%)

Pathological N category

ypN0
30 (56.6%)

ypN1
15 (28.3%)

ypN2
8 (15.1%)

Pathological stage

0
6 (11.3%)

I
10 (18.9%)

II
17 (32.1%)

III
20 (37.7%)

Tumor regression grade*

0
1 (1.9%)

1
21 (39.6%)

2
12 (22.6%)

3
12 (22.6%)

4
5 (9.4%)

Pathological LLN status

Positive
12 (22.6%)

Negative
41 (77.4%)

Histologic grade

Moderate
42 (79.2%)

Poor/Mucinous/signet
11 (20.8%)

Blood vessel invasion

Yes
11 (20.8%)

No
42 (79.2%)

Perinervous invasion

Yes
12 (22.6%)

No
41 (77.4%)
Cost-effectiveness analysis of contemporary first-line (1L) agents in locally advanced/metastatic urothelial carcinoma (la/mUC).
Authors: Naqvi Syed Arsalan Ahmed , Faisal Kunwer Sufyan , Raina Ammad , Khakwani Kaneez Zahra Rubab , Riaz Zaryab Bin , Shah Vishal S. , Cobran Ewan Kemar , Singh Parminder , Hussain Syed A. , Bryce Alan Haruo , Riaz Irbaz Bin
Published: October 2024

4591

Background:
EV-302 and CheckMate 901 demonstrated significant survival benefit with enfortumab vedotin-pembrolizumab (EVPembro) and gemcitabine-cisplatin-nivolumab (GemCisNivo) as 1L therapy, respectively, in patients (pts) with la/mUC. However, whether these treatments are cost-effective or not remains unclear.
Methods:
A three-state Markov model (progression-free, progression and death) was developed. State utilities were derived from published literature. State transition probabilities were informed from point-probabilities and hazard ratios for OS and PFS obtained from the latest follow-up of eligible trials. Average sales price (2024 USD) for individual treatments (excluding ancillary charges) were obtained from the center of medicare and medicaid services (US payer’s perspective). Treatment strategies were modeled in accordance with the dose/schedule reported in the eligible trials. Pts who received GemCis or Gem-carboplatin (GemCarbo) and did not progress were modeled to receive Avelumab maintenance. Half-cycle corrected costs and utilities were accrued over a 10-year lifetime horizon and were discounted at 3%. Monte Carlo simulation was used to estimate quality adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). A willingness-to-pay threshold (WTP) of 100,000$ per QALY was used.
Results:
In cisplatin-eligible pts, GemCisNivo demonstrated a 0.8 QALY gain over GemCis at an ICER of 21,127 ($/QALY). GemCisNivo was also associated with an incremental net monetary benefit (INMB) of 63,099$ relative to GemCis. EVPembro demonstrated a 2.4 QALY gain over GemCis at an ICER of 915,283 and a 1.6 QALY gain over GemCisNivo at an ICER of 1,406,308. In cisplatin-ineligible pts, EVPembro demonstrated a 2.4 QALY gain over Gem-carboplatin (GemCarbo) at an ICER of 934,761. Price threshold analyses demonstrated that EVPembro is likely to be cost-effective at a cost of 12,344$ for cisplatin-eligible and 13,374$ per cycle for cisplatin-ineligible pts (original cost: 35,665.60$ per cycle). Sensitivity analysis using a total of 12 cycles for EVPembro showed cost-effectiveness at an ICER of 69,594 relative to GemCisNivo in cisplatin-eligible pts, and at an ICER of 53,099 relative to GemCarbo in cisplatin-ineligible pts.
Conclusions:
In terms of US payer’s perspective, GemCisNivo is most likely to be cost-effective in cisplatin-eligible pts at the WTP of 100,000 $/QALY. Limiting the number of cycles for EVPembro may render it as a cost-effective 1L treatment in la/mUC pts regardless of cisplatin-eligibility status.
A multi-institutional observer study of AI-aided oncologists' performance on treatment response assessment of bladder cancer.
Authors: Joshi Monika , Sun Di , Alva Ajjai Shivaram , Palmbos Philip , Zakharia Yousef , Garje Rohan , Chan Heang-Ping , Cohan Richard H. , Hadjiiski Lubomir
Published: October 2024

4599

Background:
Neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) results in a complete response of 30-40%. The remaining patients who do not benefit from this approach are at risk for disease progression prior to RC. Prompt accurate treatment response assessment (TRA) of NAC prior to RC is crucial to guide treatment and minimize toxicity. Our study evaluated the impact of artificial intelligence (AI)-based decision support system (CDSS-T) on oncologists’ performance in identifying patients who respond completely (stage T0) to NAC.
Methods:
We conducted a multicenter retrospective-observational study. The pathological cancer stage after NAC f/u RC served as the reference standard. CT Urograms (CTU) of 123 patients were collected, with a total of 157 evaluable imaging pairs including pre- and post-NAC CTU (N of T0=40). Five oncologists from 3 institutions participated. We randomly selected 51 CTU pairs for each oncologist, and each one read the set of 51 cases twice with a washout period of 3 weeks to eliminate reading memory. Each reading session included sequential reading without and then with the aid of CDSS-T. The CDSS-T was developed by combining radiomics and deep-learning AI predictions. Inter-observer performance was analyzed by the ROC iMRMC method, and intra-observer performance measured by Krippendorff’s alpha (agreement: α) and Bland–Altman (variability: standard deviation (SD)) methods.
Results:
With CDSS-T aid, the 5 oncologists had a higher mean area under the curve (AUC) and smaller SD for both first readings (0.77±0.08 without, 0.86±0.07 with CDSS-T) and second readings (0.77±0.09 without, 0.84±0.04 with CDSS-T). With aid they also had higher intra-observer agreement (α: 0.70±0.05 without, 0.84±0.04 with CDSS-T) and smaller intra-observer variability (SD: 26.28±2.69 without, 19.75±2.86 with CDSS-T).
Conclusions:
CDSS-T improves oncologists’ accuracy in TRA, increases intra-observer agreement, and reduces intra-observer variability. A prospective study is ongoing in MIBC to validate the findings.

Reading 1 (AUC)
Reading 2 (AUC)
Intra-observer agreement α
Intra-observer variability SD

Oncologists

w/o CDSS-T

w/ CDSS-T

w/o CDSS-T

w/ CDSS-T

w/o CDSS-T

w/ CDSS-T

w/o CDSS-T

w/ CDSS-T

#1
0.65
0.75
0.73
0.78
0.69
0.83
30.46
21.57

#2
0.81
0.85
0.82
0.87
0.64
0.80
26.08
19.07

#3
0.81
0.89
0.77
0.83
0.73
0.85
26.05
18.67

#4
0.73
0.88
0.64
0.83
0.69
0.89
22.92
16.01

#5
0.86
0.93
0.87
0.87
0.77
0.80
25.91
23.45

Mean±SD
0.77±0.08
0.86±0.07
0.77±0.09
0.84±0.04
0.70±0.05
0.84±0.04
26.28±2.69
19.75±2.86
Addition of the MUC-1 vaccine tecemotide to neoadjuvant systemic therapy for patients with early breast cancer: Survival results from the prospective randomized ABCSG 34 trial.
Authors: Singer Christian F. , Hlauschek Dominik , Pfeiler Georg , Egle Daniel , Bartsch Rupert , Suppan Christoph , Pichler Angelika , Petru Edgar , Greil Richard , Rudas Margaretha , Seifert Michael , Petzer Andreas , Fitzal Florian , Bago-Horvath Zsuzsanna , Filipits Martin , Soelkner Lidija , Fesl Christian , Gnant Michael
Published: October 2024

587

Background:
MUC1 glycoprotein is overexpressed in over 90% of breast cancers. It is involved in oncogenesis and confers resistance to anti-cancer therapies,

thus representing a promising therapeutic target. Tecemotide (liposomal BLP25; Stimuvax) is a MUC1-based therapeutic cancer vaccine. The aim of the prospective, multicenter randomized two-arm phase-II ABCSG 34 trial was to investigate the efficacy and safety of tecemotide in patients with early BC when given concomitantly with neoadjuvant Standard-of-Care (SoC) treatment.
Methods:
400 patients with HER2- early BC were randomized 1:1 to receive preoperative SoC treatment with or without tecemotide: Postmenopausal women with luminal A tumors received 6 months of letrozole as SoC, while postmenopausal patients with TNBC, luminal B tumors, in whom chemotherapy was considered to be SoC, and all premenopausal patients received 4 x EC and 4 x Docetaxel q3w. Primary endpoint was Residual Cancer Burden (RCB0/I) at the time of surgery, long-term outcomes were measured as part of a translational project. Distant recurrence free survival (DRFS) and overall survival (OS) were analyzed with Cox regression models.
Results:
Long-term outcome data were available for 291 women of whom 236 had received chemotherapy as SoC: In these patients with evaluable RCB, the addition of tecemotide to neoadjuvant SoC was not associated with a significant increase in RCB0/I (36.4% versus 31.5%, p=0.42; 40.5% vs 34.8%, p=0.37 for the chemotherapy cohort). However, after a follow-up of 7 years, 80.8% of patients who had received SoC + tecemotide were alive and free from metastasis
versus
64.7% who had received SoC alone (HR for DRFS: 0.53, 95% CI 0.34 - 0.83,
p
=0.005); 83.0%
versus
68.2% were still alive (HR for OS 0.53, 95% CI 0.33-0.85,
p
=0.008). Women who had received chemotherapy + tecemotide had a particularly good outcome with a DRFS of 81.9% vs 65.0% (HR 0.50, 95% CI 0.31 – 0.83, p=0.007), and an OS of 83.6% vs 67.8% (HR 0.51, 95% CI 0.30 – 0.88, p=0.016).
Conclusions:
The MUC-1 vaccine tecemotide, when added to standard neoadjuvant systemic therapy, markedly improved DRFS and OS. Despite the exploratory nature of this observation, this is the first significant and profound long-term survival benefit of an anti-cancer vaccine in breast cancer patients reported to date. Additional studies are needed to understand in more detail the underlying mechanisms, and the optimal use of cancer vaccines in breast cancer treatment.
Clinical trial information: 2011-004822-85
.
Heterogeneity of immune status in patient-derived malignant pleural effusion and ascites: Relationship to the ex-vivo efficacy of a HER2-targeted tri-specific antibody and a novel cytokine fusion protein.
Authors: Liu Liming , Han Zhen , Fan Yang , Pan Qi , Kang Ping , Sun Zhijian
Published: October 2024

e13000

Background:
Malignant pleural effusion (MPE) and malignant ascites (MA) are common complications of malignant tumors, often indicating that the malignant tumors have reached an advanced stage, leading to a shorter survival. Historical studies have shown that the effusion or asities are deficient in innate immunity and/or adaptive immunity. It would be a high therapeutic value if the immune status (deficiency or exhaustion) in this tumor microenvironment can be corrected using innate and adaptive immune targeting molecules. Here we have studied the immune status of one MPE sample from an advanced Her2 positive breast cancer patient and one MA sample from an advanced ovarian cancer patient; and used a novel tri-specific molecule targeting Her2, macrophage and NK cell (IAMA-004) and a novel Fc-cytokine fusion protein (IAMA-005) to treat the cells from MPE or MA samples to determine the efficacy in the killings of tumor cells and the modulation of IFN-γ and Granzyme B levels.
Methods:
A pleural effusion sample from a 61-year-old female patient suffering from breast cancer lung metastasis and an ascitic fluid sample from a 58-year-old female patient with poorly differentiated advanced ovarian cancer were collected. The cells were immunophenotyped and treated with IAMA-004, IAMA-005, anti-PD1 or control. The killing of Her2 positive or EpCAM positive tumor cells and the levels of IFN-γ and Granzyme B were measured.
Results:
MPE immune status: NK cells, 6.47%; Macrophages, 2.11% (M1, 0.06%; M2, 0.33%); CD3
+
T cells, 5.47%; CD4
+
T cells, 2.93%; CD8
+
T cells, 1.66%; Treg, not detectable. IAMA-004 and IAMA-005 enhanced the killing of Her2 positive tumor cells by ~30% and ~40% respectively; Herceptin plus TTI-622 was not able to enhance the tumor cell killing. In combination with nivolumab, IAMA-004 was able to enhance the Granzyme B and IFN-γ secretion significantly without enhancing the tumor cell killing. Ascites immune status: NK cells, 0.5%; macrophage, 10.74% (M1, 0.31%; M2 0.05%); CD3
+
T cells, 5.98%; CD4
+
T cells, 4.36%; CD8
+
T cells, 0.97%; Treg, not detectable. While anti-PD1 antibody was not able to kill the tumor cells over the background, IAMA-004, IAMA-005 or Herceptin plus TTI-622 was able to enhance the tumor cell killing over the background more than 2.5-fold. Addition of anti-PD1 to IAMA-004 or IAMA-005 did not further increase the efficacy. The immune status of MPE being NK competent while MA being macrophage competent seems to determine the efficacy of the respective therapeutic molecules.
Conclusions:
Immune status from MPE or MA are heterogenous in both adaptive and innate immunity. Using combinations of innate immune targeting therapeutics and adaptive immune check point inhibitors may be able to correct the specific deficiency with precision and effectively treat these diseases.
Survival and safety analysis of eribulin in Indian patients with metastatic breast cancer: A real world clinical experience.
Authors: Goyal Pankaj , Doval Dinesh Chandra , Jain Shweta , Talwar Vineet , Goyal Sumit , Batra Ullas , Saha Rajat , Goel Varun , Jain Parveen , Sharma Mansi , Mathighatta Shivarudraiah Shivashankara Swamy , Jain Arpit , Upreti Kalpana , Pasricha Sunil , Gupta Manoj , Mehta Anurag , Dewan Abhinav , Mukherjee Anindya , Saha Sekhar , Basu Dharmishtha Ashis
Published: October 2024

e13002

Background:
Eribulin is a synthetic non-taxane anti-microtubule agent approved in India for the second line of treatment of locally advanced or metastatic breast cancer. Eribulin has shown to improve overall survival (OS) in various subgroups of patients with metastatic breast cancer (MBC) who were pretreated with an anthracycline and taxane. However, efficacy and safety data for eribulin in Indian patients with MBC is limited. Therefore, this real world study assessed the clinical outcomes of eribulin in heavily pre-treated MBC Indian females.
Methods:
Histologically confirmed adult MBC patients who received eribulin over several lines of therapy were retrospectively analysed. Socio-demographic, clinical, pathology, imaging, and therapy records were reviewed. The progression-free survival (PFS), overall survival (OS), tumor response and safety were evaluated.
Results:
A total of 189 patients were included and out of these patients 145 patients were analysed. The median age of patients was 52 years (range: 28-71). Eribulin was used as a 2
nd
, 3
rd
, 4
th
and ≥ 5
th
line chemotherapy agent in 17 (11.72%), 27 (18.62%), 44 (30.34%) and 57(39.31%) of MBC patients, respectively. In the overall population, the objective response rate (ORR) was 7.58%, while the clinical benefit rate (CBR) was 15.48%. The median PFS and OS were 3.86 (95% CI: 3.18-4.54) and 11.56 (95% CI: 8.72-14.40) months respectively. There was positive correlation between the number of eribulin cycles and the outcomes of survival, with patients getting more than 3 cycles having significantly superior OS and PFS. On subgroup analysis, there was no significant difference in the outcomes of survival on the basis of hormone receptor and her-2 status, however the patients who had more than 3 metastatic sites had significantly lower survival outcomes. The anthracycline and taxane refractory (progression within 6 months after their last anthracycline/taxane dose) patients had significantly (p<0.001) lower median PFS as compared to anthracycline and taxane sensitive patients (2.96 months vs 5.23 months) and (2.86 months vs 4.46 months) respectively. Among the grade ≥3 toxicities, neutropenia was 26.21%, anemia was 13.10%, thrombocytopenia was 6.21% and mucositis was 8.97%. The grade ≥2 peripheral neuropathy was seen in 28.97% patients and 21.38% patients had gastro-intestinal symptoms.
Conclusions:
This study confirms that Eribulin is effective and has manageable toxicity in patients with MBC. It should be considered as the strategy of several chemotherapy lines in MBC.
Real world experience with cyclin dependent kinase inhibitors in metastatic breast cancer from India.
Authors: Goyal Pankaj , Mukherjee Anindya , Tripathi Rupal , Doval Dinesh Chandra , Talwar Vineet , Goyal Sumit , Batra Ullas , Saha Rajat , Jain Parveen , Goel Varun , Sharma Mansi , Mathighatta Shivarudraiah Shivashankara Swamy , Jain Arpit , Mehta Anurag , Upreti Kalpana , Gupta Manoj , Pasricha Sunil , Saha Sekhar , Basu Dharmishtha Ashis , Dewan Abhinav
Published: October 2024

e13003

Background:
Patients in thehormone receptor positive/ herceptin2- (HR+/HER2-) subset have better prognosis among all molecular sub types of breast cancer, however, most patients ultimately progress on treatment with traditional endocrine therapies. The present study was conducted to evaluate the real world experience with Cyclin dependent kinase (CDK) 4/6 inhibitors Palbociclib and Ribociclib by evaluating the efficacy and toxicity profile in HR+/HER2- metastatic breast cancer.
Methods:
Thisstudy was conducted on the HR+/HER2- metastatic breast cancer patients who received Palbociclib/ Ribociclib in the first line or recurrent setting between January 2021 and January 2023 along with endocrine therapy. Clinical and demographic information and survival data was retrieved from the Hospital medical records.
Results:
Among a total of143 patients, 93 and 50 patients had received Palbociclib and Ribociclib, respectively. The most common factors in both the groups were age group 45-64 years (65.7%), postmenopausal status (65.7%), ECOG Performance status 1 (46.2%) and denovo disease at presentation (58%). The overall response rate was 90.2%. Majority of the patients showed partial response (64.3%) followed by stable disease (20.3%) in either group. In the patients receiving Palbociclib, a better median progression free survival (PFS) was observed in patients with ECOG performance status (PS) 1 (27.3 months, p-value < 0.0001), denovo disease (17.5 months, p-value 0.0155), first line hormonal therapy (22.5 months, p-value < 0.0001) and no prior chemotherapy (20.3 months, p-value 0.0001). Similarly, in the patients receiving Ribociclib, a better median PFS was observed in patients with ECOG PS 1 (22.2 months, p-value < 0.0001), denovo disease (21.7 months, p-value 0.0042), first line hormonal therapy 22.5 months (p-value < 0.0001) and no prior chemotherapy (21.7 months, p-value < 0.0001). On multivariate analysis, the factors significantly associated with PFS were ECOG PS, line of hormone therapy and prior chemotherapy (p-values < 0.0001, < 0.0001 & 0.0269, respectively). Anaemia & transaminitis were the most common toxicities in both drug cohorts [Palbociclib (97.8% & 75.3%, respectively) & Ribociclib (96.5% & 82%, respectively). Overall, dose modification due to toxicity was not required in 67.8% patients.
Conclusions:
The present study shows the real world experience with the effectiveness and tolerability of CDK inhibitors in metastatic breast cancer in India. However, large scale multi-centric studies are required to evaluate the pan India experience with these inhibitors.
T-DM1 in Chinese patients with Her2-positive metastatic breast cancer: A multi-center, retrospective, real world study.
Authors: Zhang Ruyan , Li Huiping , Zhang Pin , Hao Chunfang , Zhao Wenhui , Mo Xueli
Published: October 2024

e13026

Background:
In the pivotal EMILIA and THRESA study, the proportion of Chinese patients in the clinical trials was very low (17% of Asian patients, 87 patients in EMILIA), and no patients in the trials were previously treated with pertuzumab.
Methods:
We enrolled patients with Her2-positive metastatic breast cancer who received T-DM1 in metastatic setting between March 2020 and August 2023 in Peking University Cancer Hospital and five other medical centers. The primary endpoint was progression free survival (PFS), and secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety.
Results:
A total of 172 patients who had received at least two cycles of treatment were included in the efficacy and safety analysis. The median age was 53 years (range, 24–87years). The median number of treatment lines was three(range:1-12). 47(27.3%) patients were treated in first or second line and 125(72.7%) patients were treated in third- and above line. 79% and 61% patients had previously received pyrotinib/lapatinib and pertuzumab, respectively. With a median follow-up of 7.8 months (range: 1.3-42.2), progressive disease (PD) occurred in 103 of 172 patients (59.9%), and 26 deaths (15.1%) occurred. The median PFS was 5.1 months (95% CI: 3.9-6.3m). OS was not reached. The ORR was 17.4%, and DCR was 80.2%. Cox regression analysis showed that brain metastasis, lung metastasis and HER2 2+ in IHC were associated with shorter PFS. And the PFS of patients with previous pertuzumab treatment, liver metastasis, and more treatment lines tended to be shorter, but the difference was not statistically significant. Most AEs were grade 1–2 and manageable, grade 3 or higher adverse events were mainly thrombocytopenia(26 patients [15.1%]) and elevation of liver enzymes (7 patients [4.1%]). 36 patients (20.9%) experienced at least one dose reduction.
Conclusions:
In this real world study, in which more than half of the patients received pertuzumab previously, and more than 20% had brain metastasis, the median PFS was shortened as compared with the EMILIA trial and THERESA trial results. However, multivariate analysis suggested that previous exposure of pertuzumab did not affect the PFS of T-DM1, and patients with HER2 2+ and lung metastasis may not be the advantageous population for T-DM1 treatment. Thrombocytopenia was a dose-limiting toxicity of T-DM1, and most patients could tolerate it well after dose adjustment.
Primary Results of NRG-RTOG1106/ECOG-ACRIN 6697: A Randomized Phase II Trial of Individualized Adaptive (chemo)Radiotherapy Using Midtreatment
18
F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Stage III Non–Small Cell Lung Cancer
Authors: Kong Feng-Ming (Spring) , Hu Chen , Pryma Daniel A. , Duan Fenghai , Matuszak Martha , Xiao Ying , Ten Haken Randall , Siegel Marilyn J. , Hanna Lucy , Curran Walter J. , Dunphy Mark , Gelblum Daphna , Piert Morand , Jolly Shruti , Robinson Clifford G. , Quon Andrew , Loo Billy W. , Srinivas Shyam , Videtic Gregory M. , Faria Sergio L. , Ferguson Catherine , Dunlap Neal E. , Kundapur Vijayananda , Paulus Rebecca , Siegel Barry A. , Bradley Jeffrey D. , Machtay Mitchell
Published: October 2024

PURPOSE

NRG-RTOG0617 demonstrated a detrimental effect of uniform high-dose radiation in stage III non–small cell lung cancer. NRG-RTOG1106/ECOG-ACRIN6697 (ClinicalTrials.gov identifier:
NCT01507428
), a randomized phase II trial, studied whether midtreatment
18
F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) can guide individualized/adaptive dose-intensified radiotherapy (RT) to improve and predict outcomes in patients with this disease.

MATERIALS AND METHODS

Patients fit for concurrent chemoradiation were randomly assigned (1:2) to standard (60 Gy/30 fractions) or FDG-PET–guided adaptive treatment, stratified by substage, primary tumor size, and histology. All patients had midtreatment FDG-PET/CT; adaptive arm patients had an individualized, intensified boost RT dose to residual metabolically active areas. The primary therapeutic end point was 2-year centrally reviewed freedom from local-regional progression (FFLP), defined as no progression in or near the planning target volume and/or regional nodes. FFLP was analyzed on a modified intent-to-treat population at a one-sided
Z
-test significance level of 0.15. The primary imaging end point was centrally reviewed change in SUV
peak
from baseline to midtreatment; its association with FFLP was assessed using the two-sided Wald test on the basis of Cox regression.

RESULTS

Of 138 patients enrolled, 127 were eligible. Adaptive-arm patients received a mean 71 Gy in 30 fractions, with mean lung dose 17.9 Gy. There was no significant difference in centrally reviewed 2-year FFLP (59.5% and 54.6% in standard and adaptive arms;
P
= .66). There were no significant differences in protocol-specified grade 3 toxicities, survival, or progression-free survival (
P
> .4). Median SUV
peak
and metabolic tumor volume (MTV) in the adaptive arm decreased 49% and 54%, from pre-RT to mid-RT PET. However, ΔSUV
peak
and ΔMTV were not associated with FFLP (hazard ratios, 0.997;
P
= .395 and .461).

CONCLUSION

Midtreatment PET-adapted RT dose escalation as given in this study was safe and feasible but did not improve efficacy outcomes.
The Aggrieved Personality of Rights
Authors: Hyde Carrie
Published: October 2024

The refugee is typically understood as a uniquely modern figure, but US refugee debates and legislation are as old as the country. This essay considers how eighteenth-century debates about refugees can defamiliarize and enrich narratives about the US rights tradition that Hannah Arendt and others have developed based on post–World War accounts of refugees. Drawing on the first US refugee act in 1798, the essay moves beyond the iconic universalisms of natural rights and the abstract model of citizenship associated with it by identifying a grievance-based tradition of settler rights characterized by individualized narratives of patriotic service and political injury. The first section of the essay distinguishes the contemporary, post–World War association of “refugee” with statelessness from an earlier, protection-based understanding of the term that is rooted in its etymological connection with the safety of refuge. The second section uses Thomas Paine’s self-characterizations as a “refugee” to reframe his better-known contributions to rights philosophy. The third section concludes by reading the twenty-seven grievances in the Declaration of Independence as the most canonical example of what the essay calls the “aggrieved personality of rights”: the personal allegiances, circumstances, and injuries that inspire individuals to seek redress in the language of rights.