bluuebunny/crossref_metadata_2025 huggingface dataset:
Depression and poor sleep: neglected prevalent issues among adult epileptic patients
Authors: Fathy Sabah E. , AbdAllah Amany M. , El-Maghawry Hala Ahmed , Ali Lamis Ibrahim , Helal Rania Y.
Published: January 2024

Background

Psychiatric comorbidities, and sleep disorders, are prevalent in adults with epilepsy (AWE). Good control of epilepsy can help AWE lead a normal fruitful life and incorporate in daily activities as others. This study aims to assess the frequency, risk factors of depression, and poor sleep quality among patients with epilepsy and examine their relation with epilepsy control.

Methods

This cross-sectional study was accomplished during the period from January to October 2023 involving 179 AWE. All were exposed to complete history taking: stressing on personal data, evaluation of medication adherence using the modified Morisky scale, sleep quality using the Pittsburgh Sleep Quality Index, and depressive symptoms evaluated by the Zagazig Depression Scale.

Results

Depression was reported in 22.2% of studied patients; while 44.4% had poorer epilepsy control. Poor sleep quality was reported in 35.2% of epilepsy patients and was associated with non-adherence and poor seizure control. Depression increased the risk of poor control by about 16-folds. Non-adherence was associated with depression and poor sleep quality and was one of the predictors of poor epilepsy control.

Conclusion

Depression and poor sleep quality can impair the outcome of PWE and also there is a strong association between depression and poor sleep quality among PWE and both impair seizure control.
Insights from a retrospective study: an understanding of pediatric colorectal carcinoma
Authors: Guzmán Sofia Brenes , García Edgar Fernando Oliver , Rojas Edgar Guillermo Lazcano , Tinajero Alfa Guadalupe Barraza , Meza Daniela Hernández , Chávez Jose Luis González , Camacho Edgar Melo , Enríquez Juan Carlos Nuñez
Published: January 2024

Pediatric colorectal cancer, comprising just 1% of childhood cancers, has surged among young individuals, underscoring its significant health impact. Diagnostic challenges arise from atypical presentation and nonspecific symptoms in 90% of cases, leading to delayed detection in 19%.

Methods A 2-year retrospective study of pediatric colorectal carcinoma cases was conducted across a specialized surgical pediatric center. Data were gathered, including age, symptoms, diagnostics, treatments, and outcomes.

Results Six colorectal carcinoma cases (median age, 16) were documented, mainly in males (66%). Predominant histological types included mucinous adenocarcinoma and signet ring cell carcinoma. Metastasis was present in all cases, with symptoms including hematochezia (83%), abdominal pain (100%), weight loss (66%), and anemia (100%). Diagnosis often faced misidentification, fostering disease progression and metastasis. Various diagnostic and treatment modalities were employed, including surgery and neo-adjuvant or adjuvant chemotherapy.

Conclusion Swift detection and intervention for pediatric colorectal carcinoma are pivotal. Efficient diagnostics and heightened awareness among medical professionals and the public are imperative. Early surgical intervention remains a cornerstone, especially for patients with pertinent family histories and characteristic symptoms. Tailored guidelines for pediatric patients are needed to enhance outcomes and survival.
Can non-contrast magnetic resonance imaging replace contrast-enhanced computerized tomography in the local staging of pediatric renal tumors?
Authors: Romeih Marwa , Mahrous Mary Rabea , Raafat Tarek Ahmed , Mahmoud Esmat
Published: January 2024

Background

Renal tumors account for approximately 6–7% of the total incidence of pediatric cancers. Wilms tumor (WT) is the most common renal malignancy observed in the pediatric population under 5 years old. Computed tomography (CT) is used for staging of the renal tumors. Magnetic resonance imaging (MRI) offers enhanced soft tissue resolution and provides more comprehensive insights into tumor extension through the capsule, including tumor infiltration into the renal vein or IVC. MRI is a noninvasive imaging modality that does not involve any radiation hazards, making it safe for children. In addition, MRI can be performed without the administration of contrast agents in patients with impaired renal function. Therefore, MRI plays a vital role in screening, staging, preoperative evaluation, and follow-up. Diffusion-weighted imaging (DWI) is a functional tool that aids in locating the most receptive tumoral region to guide confirmatory biopsies. In this study, we aim to evaluate the potential value of non-contrast MRI in staging pediatric renal tumors compared to contrast-enhanced CT.

Results

This study included 50 patients presented with renal mass, with ages ranging from 1 to 8 years and a mean age of 4.27 ± 1.27 (mean ± SD). The final diagnosis was Wilm’s tumor at 86%, clear cell sarcoma at 4%, rhabdoid tumor at 4%, rhabdomyosarcoma at 2%, and nephroblastomatosis with no malignant transformation at 4%. CT accurately diagnosed stages 4 and 5 in agreement with pathological findings while upstaging the other cases, with a CT sensitivity of 90.91%, specificity of 82.35%, PPV of 92%, and NPV of 84%. MRI is superior to CT in stages 1 and 3, accurately diagnosing stages 2, 4, and 5, with a sensitivity of 93.30%, specificity of 95.65%, PPV of 95%, and NPV of 97%.

Conclusions

Non-contrast MRI could be considered the optimal radiation-free imaging modality in staging pediatric renal tumors mainly Wilm’s tumor as it offers high sensitivity and specificity of capsular and vascular infiltration, compared to contrast-enhanced CT especially in cases with impaired renal functions.
The impact of IT governance and data governance on financial and non-financial performance
Authors: Naguib Hend Mohamed , Kassem Hossam Magdy , Naem Abd El-Hamed Mostafa Abou
Published: January 2024

This paper aims to examine the impact of both information technology governance (ITG) and data governance on information technology (IT) performance in the telecommunication industry. A questionnaire of 308 managers was collected from all telecommunication companies that are working in Egypt. Data were analyzed using smart partial least squares (PLS). The results showed that all the hypotheses of the study had been accepted. IT and data governance have a significant impact on both financial and non-financial performance. However, each of them has a different effect on the IT performance dimensions. The financial performance of IT department had been affected by IT governance more than data governance. Also, innovation and flexibility were the most affected by IT governance. On the other hand, data governance affected business processes and ethical compliance more than IT governance. The current study filled the gap on the literature in two ways. First, studying both IT governance and data governance as a critical factors affects financial and non-financial performance. Second, studying IT governance and data governance has become more important, especially in the telecommunication industry as it is a big challenge now to secure the data of the companies.
Role of lactate level in predicting admission need to intensive care unit and short term outcomes in patients with acute gastrointestinal bleeding
Authors: Shawky Hekmat Nashat , Kamel Hala Mostafa , Sayed Zain Elabdeen Ahmed , Abdelwahab Hossam Mahmoud
Published: January 2024

Background

One of the most common emergencies seen in emergency departments is acute gastrointestinal bleeding (GIB). It’s associated with more disease burden and mortality.

Increased venous lactate levels are common in critically ill patients, and it has been used as a possible predictor of patients’ outcomes in many critical cases, but not much is known about its predictive role in patients with acute GIB.

With increasingly limited health care resources, there has been such an interest in coast saving measures and measuring lactic acid through venous blood gases is such a simple bedside test which can be easily done to patients with acute GIB at emergency department.

Objective

This study assessed the predictable value of lactate level on hospital admission on resource use, including length of hospital stay and admission to the intensive care unit (ICU), as well as other patient-oriented outcomes, including the need for blood transfusions and endoscopy.

Patients and methods

A prospective cohort hospital based study that included 300 patients with acute GIB who presented to emergency department (ED) of Assiut University Hospital between September 2019 and June 2022 were subjected to venous blood lactate through venous blood gases.

Results

The current study enrolled 300 patients with acute GIB. Two hundred of those patients had elevated blood lactate and 100 patients had normal blood lactate. It was found that patients with elevated blood lactate had significantly prolonged hospital stay (7.38 days ± 2.05 days vs. 3.96 days ± 1.74 days; (P < 0.001). Also they had higher frequency of blood transfusion (98% vs. 72%), ICU admission (95% vs. 67%) and mortality (9% vs. 3%) in comparison to those with normal lactate level.

Conclusion

It was found that venous lactate level is an effective predictor for patient’s outcomes among patients with acute GIB.
Speech auditory brainstem responses (s-ABRs) as a new approach for the assessment of speech sounds coding
Authors: Elsayed Hagar Ahmed , Nada Ebtessam Hamed , Galhoum Dalia Helal , Elnabtity Nadia Mohamed
Published: January 2024

Background

The evoked auditory brainstem response (EABR) is an objective electrophysiological test used to assess the brainstem’s auditory neural activity. Speech ABR (s-ABR) testing using verbal stimuli gives more important details about how the brainstem processes speech inputs which enables the detection of auditory processing impairments that do not manifest in click-provoked ABR. The use of speech syllables in the s-ABR reveals an important brainstem function that plays a crucial part in reading development and phonologic achievement which is an assessment of speech syllables. The syllable /da/ is often utilized in s-ABR measurement being a global syllable that can be tested in many nations with effective experimental confidence.

Conclusion

The speech ABR is an objective, unbiased, quick test. It can be used to differentiate between many conditions such as auditory processing disorders (APD), specific language impairment (SLI), and children with academic challenges.
Correlation between tympanometric findings and adenoid hypertrophy among children without hearing loss in tertiary care hospital
Authors: Basavaraju K. P. , Ranjani S. K. , Sri Vaibhava V. , Sulhyan Sushmita
Published: January 2024

Adenoid hyperplasia is a common cause of nasal obstruction in children. Chronic infection and hypertrophy result in mouth breathing, snoring, sleep apnoea, hyponasality, sinusitis, and otitis media with effusion (OME). Some children with adenoid hypertrophy have OME in spite of having no complaints of hearing loss. Untreated OME may adversely affect the speech and intellectual development of the child.

Aim To determine whether there is a correlation between tympanometric findings and various radiological and endoscopic grades of adenoid hypertrophy.

To propose a combination of radiological and/or endoscopic assessment of adenoids and tympanometry as a screening program in patients with suspicion of adenoid hypertrophy.

Materials and methods One hundred children, presenting with one or more complaints of upper airway obstruction (UAO), suggestive of adenoid hypertrophy, without a history of hearing loss, to the OPD, were chosen for the study. X-ray nasopharynx soft tissue lateral view was done for all patients. Rigid diagnostic nasal endoscopy with 0° endoscope was conducted in only children who were cooperative and with parental consent. Tympanometry was carried out for all patients and plotted on tympanograms.

Results In our study, the mean age of children is 9.43 ± 2.430 years with gender distribution being 57% males and 43% females. The majority of children tend to present with nasal obstruction (100%), mouth breathing (83%), and snoring (56%). On both radiological and endoscopic evaluation of adenoids and correlation with tympanogram, a significantly higher number of patients with Grade 1 adenoids have a type A curve, while a significantly higher number of grade 3 adenoids patients have a type B curve and type C is significantly more prevalent in grade 2 and grade 4 adenoids (p < 0.05).

Conclusion In our study, adenoid size as measured from both adenoid X-ray and adenoid endoscopy, showed a significant association with the presence of middle ear effusion and also with eustachian tube dysfunction. This helps in early detection, prior to the development of hearing loss, making it easy to plan early intervention, and curbing the possibility of aggravation of the condition and occurrence of complications.
Fractional-order velocity-dilatation-rotation viscoelastic wave equation and numerical solution based on a constant-Q model
Authors: Han Guanghui , He Bingshou , Zhang Huixing , Wang Enjiang
Published: January 2024

Viscoelastic wave equations based on the constant- Q (CQ) model can accurately describe the amplitude dissipation and phase distortion of waves in anelastic media. However, only three velocity or displacement components can be obtained directly by solving such equations. Starting from the time-domain second-order displacement viscoelastic wave equation, we derived the decoupled P- and S-wave displacement vector viscoelastic wave equation by using the polarization difference of P- and S-wave propagation in isotropic media. The equation can be transformed into the velocity-dilatation-rotation viscoelastic wave equation containing the first-order temporal derivative and fractional Laplacian operators, which can be solved directly by using the staggered-grid finite-difference and pseudospectral methods. We use the low-rank decomposition method to approximate the derived mixed space-wavenumber domain fractional Laplacian operators for modeling wave propagation in heterogeneous attenuating media. We also demonstrated the precision of our equation by comparing the numerical solutions with the analytical solutions. Furthermore, compared with the conventional velocity-stress viscoelastic wave equation, experimental results demonstrate that our equation can separate the pure P and S waves from the mixed wavefield during wavefield continuation. In addition, it can be separated into an equation containing predominantly an amplitude attenuation or a phase distortion term.
Bulky nodal disease as distinctive prognosticator in anal cancer management.
Authors: Chie Eui Kyu , Chun Seok-Joo , Kim Eunji , Jang Won Il , Kim Mi-Sook , Kang Hyun-Cheol , Kim Byoung Hyuck
Published: January 2024

1

Background: This study aimed to investigate the prognostic value of bulky nodal involvement in patients with squamous cell carcinoma of anus treated with definitive chemoradiotherapy. Methods: Medical records of patients with anal squamous cell carcinoma receiving definitive chemoradiotherapy at three medical centers from 2004 to 2021 were retrospectively analyzed. Exclusion criteria were (1) distant metastasis including non-regional nodal involvement at diagnosis, (2) 2D radiotherapy, and (3) salvage treatment for local relapse. Bulky nodal disease was defined as node with long-diameter 2cm or greater. Results: A total of 104 patients were accrued, consisting of 51 patients without, 46 patients with non-bulky, and 7 patients with bulky nodal involvement. Median follow-up duration was 54.0 months (range, 6.4-162.2 months). Estimated progression-free survival (PFS), loco-regional recurrence free survival (LRRFS) and overall survival (OS) at 5 years for patients with bulky nodal disease were 42.9%, 42.9%, and 89.4%, respectively. Compared to without or with non-bulky nodal involvement, bulky nodal involvement was significantly related with poor PFS and LR RFS. New staging incorporating bulky nodal disease as N2 stage was devised: T1-2N0-1 as stage I, T3-4N0-1 as stage II, and N2 as stage III. Estimated PFS, LRRFS, and OS at 5 years were as follows: 83.5%, 85.9%, and 91.3%, 60.9%, 67.7% and 93.3%, and 42.9%, 42.9%, and 55.6% for patients with stage I, II, and III disease, respectively (p = 0.0024 for PFS, 0.0015 for LRRFS, and 0.28 for OS, respectively). Conclusions: Patients with bulky nodal disease receiving standard chemoradiotherapy had poor survival outcomes compared to the other patient groups, suggesting the need for further treatment intensification. Moreover, incorporating bulky nodal disease into the staging system improved the prognosis predictability.
Real-world analysis of irinotecan (iri) with or without fluorouracil (5FU) in the second line treatment (2L) of metastatic colorectal cancer (mCRC).
Authors: Lentz Robert William , Hu Junxiao , Robinson Hannah Ruth , Balmaceda Nicole Baranda , Baiyee Ebot Emily Eyoung , Leal Alexis Diane , Kim Sunnie S. , Davis S. Lindsey , Messersmith Wells A. , Lieu Christopher Hanyoung
Published: January 2024

102

Background: The most used 1st line (1L) chemotherapy backbone for mCRC is fluoropyrimidine (FP) + oxaliplatin. In the 2L, iri alone or with 5FU (FOLFIRI), ± a biologic agent (biologic), are options. It is unclear whether adding 5FU to iri is beneficial following disease progression on prior FP. Methods: This study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database to identify patients diagnosed with mCRC from 01-01-2013 to 02-13-2023, who received 1L with FP + oxaliplatin ± biologic, and 2L with irinotecan ± 5FU ± biologic. Baseline patient/tumor characteristics were obtained. The number of major comorbidities was computed using ICD-9-CM/10 codes within 1 year prior to 2L (Quan, 2005). Time to next treatment (TTNT) was defined from the start of 2L to the start of next line treatment (excluding maintenance). For survival outcomes, the median survival time and 95% confidence interval (CI) were estimated using the Kaplan-Meier method. Uni- and multi-variable analyses (UVA and MVA) were performed with the cox proportional hazard model. All covariates were evaluated in UVA, and those significant were included in MVA with adjusted hazard ratio (HR) and 95% CI. Results: 3,215 patients met criteria; most previously received a biologic with 1L (70.5% prior anti-angiogenesis and 5.9% prior anti-EGFR) and had 0 structured major comorbidity diagnoses (82.1%). In the 2L, FOLFIRI was the most used chemotherapy backbone (90.6%, vs iri 9.4%), 79% of patients also received a biologic, and patients who received FOLFIRI were younger (median age 61 vs 65 years) and had better ECOG performance status (87.8% vs 81.8% ECOG 0-1). Overall survival (OS) was longer with FOLFIRI than iri (median 14.4 vs 9.8 months, p<0.001), as was TTNT (median 7.6 vs 5.3 months, p<0.001). In MVA, when controlling for age, comorbidities, CEA, ECOG performance status, and 1L, iri was associated with shorter OS than FOLFIRI (HR 1.38, 95% CI 1.21-1.57, p<0.001). In MVA, the addition of a biologic to FOLFIRI and iri prolonged OS and TTNT in some subgroups (Table). Conclusions: In this retrospective real-world analysis of 3,215 patients with mCRC who received 1L with FP + oxaliplatin ± biologic, 2L FOLFIRI was associated with longer OS compared to iri alone (both ± biologic). [Table: see text]
Peritoneal lavage cytology in patients with curative resection for stage II and III colorectal cancer: A multi-institutional prospective study.
Authors: Kobayashi Hirotoshi , Kotake Kenjiro , Sugihara Kenichi , Ajioka Yoichi
Published: January 2024

11

Background: Although various prognostic factors in patients with colorectal cancer has been reported, the usefulness of intraoperative lavage cytology in patients with colorectal cancer is controversial. The aim of this study was to clarify the usefulness of intraoperative lavage cytology in patients with curative resection for pSage II-III colorectal cancer in a prospective multicenter study. Methods: The 20 member hospitals of the Japanese Society for the Cancer of the Colon and Rectum prospectively registered the patients diagnosed as stage II or III colorectal cancer preoperatively between 2013 and 2017. Among these patients, pStage II-III patients went through analysis. Lavage cytology was performed twice during surgery. The first procedure was performed right after laparotomy, and the second was performed right after specimen retrieval. The primary endpoint of this study was an effect of lavage cytology on 5-year relapse-free survival (RFS) in patients with pStage II-III colorectal cancer. The secondary endpoint was an effect of lavage cytology on 5-year overall survival (OS) and peritoneal recurrence in patients with pStage II-III colorectal cancer. Results: A total of 1378 patients were eligible and went through analysis. The number of patients with pStage II and III colorectal cancer were 670 and 708, respectively. Among 1378 patients, 54 (3.9%) had positive cytology. The median follow-up period of the entire cohort was 5.3 years. In pStage II patients, the 5-year RFS rate with positive and negative cytology was 61.1% and 81.6%, respectively (P = 0.023). The 5-year OS rate of pStage II patients with positive and negative cytology was 67.1% and 91.7%, respectively (P = 0.0083). However, there was no difference in RFS and OS between patients with positive and negative cytology in pStage III patients. Thirty-three patients had peritoneal recurrence. The peritoneal recurrence rate was 11.8% and 1.5% in pStage II patients with positive and negative lavage cytology, respectively (P = 0.032). That was 10.5% and 2.5% in pStage III patients with positive and negative lavage cytology, respectively (P = 0.022). In total, 11.1% of patients with positive lavage cytology had peritoneal recurrence in this cohort. Conclusions: The pStage II colorectal cancer patients with negative cytology had better RFS and OS compared to those with positive cytology. Peritoneal lavage cytology was useful in predicting peritoneal recurrence after curative resection for pStage II-III colorectal cancer. Clinical trial information: UMIN000026070 .
Real-world evidence of FOLFIRI combined with anti-angiogenesis inhibitors or anti-EGFR antibodies for patients with early recurrence colorectal cancer after adjuvant FOLFOX/CAPOX therapy in Japan: A retrospective observational study using administrative database.
Authors: Sunakawa Yu , Wang Chaochen , Piao Yongzhe , Jin Long , Tanizawa Yoshinori , Cai Zhihong , Kagawa Yoshinori
Published: January 2024

110

Background: Oxaliplatin-containing regimens (FOLFOX or CAPOX) are the most common adjuvant treatments after curative resection of colorectal cancer (CRC). However, real-world evidence (RWE) of treatment sequence/outcomes for patients with early recurrence CRC after receiving adjuvant chemotherapy are limited. Methods: This retrospective cohort study was based on an administrative database in Japan. The primary objective was to describe the treatment sequence for patients with early recurrence CRC and treated by combination of FOLFIRI and anti-angiogenesis inhibitors (AAIs) or anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) after adjuvant FOLFOX or CAPOX therapy. The study included patients with CRC who underwent surgical resection, started adjuvant chemotherapy ≤3 months (mo) after the first surgery, had early recurrence of CRC (defined as initiation of FOLFIRI + AAIs/anti-EGFR mAbs second line [2L] regimen) within 1 year after adjuvant chemotherapy ended. Patient characteristics at baseline of 2L (60 days prior to 2L initiation) and treatment sequence were summarized descriptively; time to discontinuation (TTD) for adjuvant and 2L therapy were analyzed using Kaplan-Meier method. Cox proportional hazard model was used to identify risk factors associated with TTD of 2L regimen. Results: The cohort included 832 patients: median (range) age was 67 (24-86) years, 56.4% males, 65.5% with left-sided CRC. Most patients received CAPOX (71.3%) as adjuvant therapy. Median (95% CI) duration of adjuvant therapy was 5.4 mo (5.3-5.5). As 2L therapy, 72.5% and 27.5% of patients received FOLFIRI + AAIs (AAIs group) and FOLFIRI + anti-EGFR mAbs (anti-EGFR group), respectively. Median TTD (95% CI) of the AAIs and anti-EGFR groups in 2L were 6.2 mo (5.8-6.9) and 6.1 mo (5.2-7.4), respectively. Among patients with recurrence within 6 mo (72.6%), the median TTD (95% CI) for AAIs and anti-EGFR groups were 6.1 mo (5.5- 6.5) and 5.8 mo (5.1-7.8), respectively. Among patients with recurrence during 6 to 12 mo (27.4%), the median TTD (95% CI) of AAIs and anti-EGFR groups were 8.1 mo (6.1-9.2) and 6.2 mo (4.6-8.0), respectively. Age ≥70 years was negatively associated with TTD of 2L, HR = 1.19 (95% CI: 1.02-1.39); p=0.03. Conclusions: This is the first RWE based on administrative data on treatment sequence/ outcomes for patients with early recurrence CRC treated by FOLFIRI + AAIs/anti-EGFR mAbs after adjuvant FOLFOX/CAPOX therapy in Japan. The treatment outcomes for patients with early recurrence CRC were similar to previous clinical trials in 2L advanced CRC. The results suggested that these two 2L regimens had similar TTD; however, the timing of relapse may influence the efficacy of AAIs and anti-EGFR mAbs.
Efficacy and safety of trifluridine/tipiracil in combination with bevacizumab in older and younger patients with refractory metastatic colorectal cancer: A subgroup analysis of the phase 3 SUNLIGHT trial.
Authors: Taieb Julien , Prager Gerald W. , Fakih Marwan , Ciardello Fortunato , Van Cutsem Eric , Elez Elena , Cruz Felipe Melo , Wyrwicz Lucjan S. , Stroyakovskiy Daniil , Papai Zsuzsanna , Poureau Pierre-Guillaume , Liposits Gabor , Cremolini Chiara , Bondarenko Igor , Modest Dominik Paul , Roby Lucas , Barboux Valentine , Amellal Nadia , Tabernero Josep
Published: January 2024

111

Background: SUNLIGHT, an international, open-label, randomized, phase 3 study comparing trifluridine/tipiracil (FTD/TPI) + bevacizumab (FTD/TPI + bev) to FTD/TPI monotherapy in patients with refractory metastatic colorectal cancer (mCRC), demonstrated a 3.3-month increase in overall survival from 7.5 months with FTD/TPI monotherapy to 10.8 months with FTD/TPI + bev (HR, 0.61; 95% CI: 0.49–0.77; P<0.001). This subgroup analysis of SUNLIGHT examined efficacy and safety outcomes by age. Methods: In SUNLIGHT, patients with mCRC with ECOG PS of 0-1 and two prior treatment regimens were randomized to receive FTD/TPI + bev or FTD/TPI. A subgroup analysis was performed to evaluate efficacy and safety outcomes in patients aged <65, 65-74, and ≥75 years. Results: Among 492 randomized patients (n=246 FTD/TPI + bev; n=246 FTD/TPI), 56%, 32%, and 12% were aged <65, 65-74, and ≥75 years, respectively. Concerning overall survival, hazard ratios for FTD/TPI + bev vs FTD/TPI monotherapy were 0.65 (95% CI: 0.48–0.87), 0.64 (95% CI: 0.43–0.94), and 0.49 (95% CI: 0.27–0.90) in patients aged <65, 65-74, and ≥75 years, respectively. Regardless of age, patients receiving FTD/TPI + bev experienced improved progression-free survival and improved time to worsening of ECOG PS to ≥2. Among FTD/TPI + bev treated patients, frequency of any-cause severe adverse events (AEs) was slightly higher in the 65-74 subgroup [69% (<65); 80% (65-74); 67% (≥75 years)]. Frequency of grade 3 and 4 neutropenia was also slightly higher in the 65-74 subgroup [38% (<65); 54% (65-74); 42% (≥75 years)]. AE-related discontinuation rates were similar across age subgroups [11.6% (<65 years), 13.2% (65-74), and 16.7% (≥75 years)]. Conclusions: The results of this subgroup analysis demonstrate the efficacy benefit and tolerability of FTD/TPI + bevacizumab treatment regardless of age in refractory mCRC patients. Clinical trial information: NCT04737187 .
Initial efficacy evaluation of fruquintinib plus capecitabine versus capecitabine as maintenance treatment for metastatic colorectal cancer (mCRC): A randomized, controlled, phase Ib/II study.
Authors: Li Wenhua , Chang Jinjia , Wang Chenchen , Peng Junjie
Published: January 2024

119

Background: The standard first-line therapy followed by maintenance treatment is an optional approach to balance the efficacy and toxicity for mCRC. Fruquintinib (Fru), a highly specific inhibitor of VEGFR1/2/3, has demonstrated favorable safety and efficacy outcomes in the treatment of mCRC. In this study, we present findings from an investigation into the comparative efficacy and safety of Fru in combination with capecitabine (Cap) versus Cap as a maintenance therapy for patients (pts) with mCRC. Methods: Pts with histologically confirmed mCRC who achieved disease control (including CR/PR and SD) after at least six cycles of first-line standard chemotherapy were included in the study. During phase Ib, pts received Fru (4 mg p.o. qd, 3 weeks on/1 week off, q4w]) plus Cap (850 mg/m2, p.o. bid, d1-7 and d15-21, q4w). In phase II, pts were randomized in a 1:1 ratio to receive either Fru (RP2D, 3mg, 3 weeks on/1 week off) plus Cap or Cap alone. The primary outcome was progression-free survival (PFS). Results: By Sep 10, 2023, a total of 34 pts were enrolled in the study, and 26 pts were considered evaluable for efficacy. During Fru plus Cap (n=14) and Cap (n=12), the median age was 61.5 (39-78) and 57.5 (32-75) years. The main primary tumor side was left (64.3% / 66.7%) and approximately half of the pts harbored a RAS mutation (50.0% / 58.3%). Most pts had previously received bevacizumab therapy (57.1% /58.3%) or cetuximab (35.7% /25.0%), respectively. The mPFS was significantly improved in Fru plus Cap vs Cap (9.1 vs 3.8 months, HR: 0.289, 95% CI 0.083 to 1.01, p=0.039). Consistently, ORR (21.4% vs 0%) and DCR (92.9% vs 66.7%) were improved with Fru plus Cap. Grades 3 and 4 treatment-emergent adverse events (TEAEs) were hypertension (11.1%), oral mucositis (5.6%), voice alteration (5.6%), small intestinal obstruction (5.6%), acrodynia (5.6%) and blood bilirubin increased (5.6%) in Fru plus Cap, and diarrhea (6.3%), oral mucositis (6.3%) and acrodynia (6.3%) in Cap therapy. Conclusions: The findings suggest that Fruquintinib plus Capecitabine can be considered as a first-line maintenance therapy for metastatic colorectal cancer, as it demonstrated a promising improvement in mPFS by 5.3 months while maintaining a controlled level of safety. Clinical trial information: NCT05451719 .
A prospective multicenter phase II trial of total neoadjuvant therapy for locally advanced rectal cancer in JAPAN: ENSEMBLE-1 study.
Authors: Kagawa Yoshinori , Watanabe Jun , Ando Koji , Uemura Mamoru , Inoue Akira , Oba Koji , Takemasa Ichiro , Oki Eiji
Published: January 2024

123

Background: The short- and long-term prognosis of total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC) is elucidated in the world. We evaluated the feasibility and safety of TNT for patients with LARC in Japan. Methods: This prospective, multicenter, open-label, single-arm phase II trial was conducted at five institutions. The key eligibility criteria were age ≥20 years, LARC within 12 cm from the anal verge, and cT3-4N0M0 or TanyN+M0 at the time of diagnosis that enabled curative resection. Preoperative short-course radiation therapy (SCRT) 5 Gy × 5 days (total 25 Gy) + CAPOX (6 courses) followed by total mesorectum excision (TME) was the treatment protocol. Non-operative management (NOM) was allowed if clinical complete response (cCR) was obtained in the preoperative evaluation. The primary endpoint was the pathological complete response (pCR) rate. With a pCR rate threshold of 5%, an expected value of 28%, a one-sided significance level of 5%, and a power of at least 80%, the sample size required by the exact binomial distribution method would be ≥19 patients. Considering a few dropouts, ineligible cases, and patients in which resection was not performed, the target sample size was set to 27 patients. Results: Thirty patients (male, n=26; female, n=4; median age, 62.5 [44-74] years; cT [T2, n=1; T3, n=25; T4, n=4]; cN [N0, n=13; N1, n=13; N2, n=4]) were enrolled. The final analysis included 30 patients in total. The completion rates were 100% for SCRT and 83% for CAPOX. TME and NOM were performed in 20 and seven patients, respectively. pCR was observed in six patients (30% [95% CI 14.0%–50.8%]). The primary endpoint was met. pCR+cCR was observed in 13 (43.3%) patients at TME or restaging. There were no treatment-related deaths. Grade ≥3 (CTCAE ver. 5.0) adverse events (≥20%), including diarrhea (23.3%) and neutropenia (23.3%). The median follow-up period was 21.8 (10.9-29.6) months. Recurrences in three patients (10.0%) were observed. In NOM, regrowth (28.6%) in two patients occurred, of which one patient was performed TME and one patient is on chemotherapy. Conclusions: ENSEMBLE-1 demonstrated satisfactory pCR and cCR, and well-tolerated safety of TNT for patients with LARC in JAPAN. Further long-term prognosis observation is required. A phase III trial, ENSEMBLE (NCT05646511/jRCTs031220342) is currently ongoing in JAPAN. Clinical trial information: jRCT s051200113 .
Preliminary efficacy and safety of fruquintinib as maintenance therapy after first-line treatment in metastatic colorectal cancer (mCRC): A multicenter, randomized, open-label clinical trial (the FRONT study).
Authors: Xu Xiaojing , Yu Yiyi , Liu Qing , Wang Yan , Cui Yuehong , Li Wei , Li Qian , Feng Yi , Liang Li , Yu Shan , Lv Minzhi , Liu Tianshu
Published: January 2024

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Background: Maintenance therapy and discontinuation of treatment are options to mCRC patients who response to first-line treatment. We conducted this study to evaluate the efficacy and safety of fruquintinib as maintenance therapy after first-line treatment for mCRC. Methods: This is an ongoing, multicenter, open-label, randomized clinical trial. Patients (pts) with unresectable right-sided mCRC or RAS-mutant left-sided mCRC, who hadn’t suffer disease progression after first-line standard treatment (chemotherapy with or without bevacizumab) for four to six months, were eligible. According to the protocol, 110 patients would be randomly assigned (2:1) to fruquintinib (FR) group (4mg once daily for 21 days, followed by 7 days off in 28 day cycles) or observation (OB) group via interactive web response system. The primary endpoint was progression-free survival (PFS). Results: Up to Aug 22, 2023, 28 and 14 patients had been enrolled in FR group and OB group, of whom the median age was 61 (44 to 73) vs. 66.5 (36 to 81), including 20 (71%) vs. 10 (71%) males, respectively. 26 (93%) vs. 11 (79%) patients were RAS-mutant. In the full analysis set (FAS), the median PFS were 5.26 (95% CI: 3.71-19.12) months and 2.99 (95% CI: 1.91-4.63) months (HR=0.36; p=0.0158). 25 and 13 pts from two groups received at least one response evaluation after baseline, respectively. The disease control rate (DCR) was 88.00% (22/25) vs. 53.85% (7/13) (OR=6.29, 95% CI: 1.31-36.7; p=0.0267). As to the per-protocol set (PPS), since 6 pts in FR group initiated with a lower dose (3mg), the number of patients was 22 vs. 14. The median PFS were 6.51 (95% CI: 3.88-19.12) months and 2.99 (95% CI: 1.91-4.63) months (HR=0.25; p=0.0061). The DCR was 89.47% (17/19) vs. 53.85% (7/13) (OR=7.29, 95% CI: 1.32-58.9; p=0.0331). The common AEs in FR group were hypertension, hand-foot syndrome, fatigue, rash, oral mucositis, and proteinuria, while AEs of grades≥3 were hand-foot syndrome, hypertension, oral mucositis, and proteinuria. Conclusions: Fruquintinib at a moderate dose level indicated better outcomes of PFS as a maintenance therapy after first-line therapy with acceptable toxicity for patients with mCRC. Clinical trial information: NCT04296019 .
Updated survival results of ALTER-C002: Anlotinib combined with CAPEOX as first-line treatment in RAS/BRAF wild-type unresectable metastatic colorectal cancer.
Authors: Liu Yue , Ding Kefeng , Xiao Qian , He Jinjie , Hu Hanguang , Du Jinlin , Zhu Yuping , Chen Jiaqi , Liu Zhuo , Wang Jianping , Sun Lifeng , Xu Dong , Li Jun , Liao Xiujun , Wang Jianwei , Cai Yibo , Cai Cheng , Jin Zhekang , Yuan Ying
Published: January 2024

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Background: Anlotinib is an oral multi-target tyrosine kinase inhibitor, mainly targeting VEGFR 1-3, FGFR 1-4, PDGFR a/b and c-kit. Previous trial had demonstrated that anlotinib monotherapy was effective and safe in advanced colorectal cancer. ALTER-C002 trial is an open-label, single-arm, phase II study, aimed to evaluate the efficacy and safety of anlotinib plus CAPEOX as first-line therapy in patients with RAS/ BRAF wild-type unresectable metastatic colorectal cancer (mCRC). The progression-free survival has been reported, preliminary results demonstrated significant antitumor activity and manageable toxicity, here we reported the overall survival results at the data cutoff of May 29, 2023. Methods: RAS/BRAF wild-type unresectable mCRC patients with no prior systemic treatment received anlotinib (12 mg p.o. qd, d1-d14, q3w), capecitabine (850 mg/m2 p.o., bid, d1-d14, q3w) and oxaliplatin (130 mg/m2 i.v., d1, q3w) for 6 cycles followed by anlotinib and capecitabine as maintenance therapy until disease progression. Tumor response was assessed every 6 weeks according to RECIST v1.1 by investigator. The primary endpoint was ORR, and secondary endpoints included safety, DCR, DOR and PFS. Results: From Nov 2019 to February 2021, 30 eligible patients were enrolled, of whom, median age was 60y (range, 32-72y), 26 (86.7%) had left colon or rectal cancer, and 25 (83.3%) had liver metastases. In previous reports, ORR, DCR, and median PFS were 76.7%, 93.3%, and 11.3 months, respectively. At a Median follow-up of 31.7 months (95% CI, 27.8-35.6), the median OS was 29.7 months (95% CI, 21.2-38.2), the 24-month OS rate was 55.0% (95%CI, 35.4-70.9%) and the 30-month OS rate was 40.6% (95%CI:21.6-58.9%). Conclusions: Anlotinib combined with oxaliplatin and capecitabine achieved considerable OS and showed potential efficacy as first-line therapy for mCRC with manageable toxicity profiles. Clinical trial information: NCT04080843 .
Real-world data of TAS-102 therapy in refractory metastatic colorectal cancer (mCRC): The experience of the University Hospital of Montreal (CHUM).
Authors: El Khoury Reem , Tehfe Jad , Ouellet Marie , Aubin Francine , Lougnarath Rasmy , Ayoub Jean-Pierre M. , Tehfe Mustapha
Published: January 2024

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Background: Colorectal cancer poses a substantial healthcare burden due to its elevated rates of diagnosis and mortality. Managing refractory metastatic cases remains a challenge in our practice due to the paucity of therapeutic options. Treatment with Trifluridine-Tipiracil (TAS-102) prolonged overall survival among patients (pts) with mCRC. This study investigates the efficacy of TAS-102 therapy in this patient population and explores various prognostic factors influencing clinical outcomes. Methods: We retrospectively reviewed the data of 53 patients with refractory mCRC treated with at least 1 cycle of TAS-102 at CHUM between March 2018 and January 2023. Multivariate and univariate analyses were employed to evaluate the impact of age, number of prior treatments, presence of KRAS mutation, gender, tumor origin, and Eastern Cooperative Oncology Group (ECOG) performance status on progression-free survival (PFS) and overall survival (OS). Survival analysis was conducted using the Kaplan-Meier method, and Cox regression analysis assessed prognostic factors. Results: The median age was 61 years (23-82), and 27 pts (50.9%) were females. Twenty-two pts (41.5%) had their primary tumor located in the left colon, 17 pts (32.1%) had right-sided tumors, and 14 pts (26.4%) with rectal tumors. 52% of pts received TAS-102 after 2 lines of therapy and 43% beyond third line. The performance status was: ECOG 0/1 in 46 pts (86.8%), and ECOG 2 in 7 pts (13.2%). In our refractory mCRC pts, median PFS was 3 months and median OS 7 months. Univariate analysis demonstrated no significant differences in PFS or OS based on patient sex, KRAS mutation status, tumor sidedness, or the number of prior treatments. In univariate and multivariate analysis ECOG 0/1 pts compared to ECOG 2 pts had a significant improvement in both PFS (HR = 0.33; p = 0.0511) and OS (HR = 0.21; p = 0.0086). Conclusions: In our real-world experience, clinical outcomes were comparable to the findings from the RECOURSE trial, suggesting improved PFS and OS with TAS-102 in heavily pre-treated mCRC patients. ECOG performance status remains a significant prognostic factor and underscores its importance in treatment decisions for this patient population.
Characterizing differential efficacy and phenotypic response to proteasome and survivin inhibitors in colorectal cancers using a high throughput organoid assay.
Authors: Zuaiter Dana , Ahirwar Parmanand , Pokal Aman G , Patel Zeelu H. , Charania Areesha A. , Crawford Chelsea L. , Sewell-Loftin Mary Kathryn , Tsung Allan , Kim Alex , Budhwani Karim I.
Published: January 2024

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Background: Conventional monolayer cell cultures and xenograft models, while useful and economical in early drug discovery, cannot predict clinical efficacy. Further, preclinical screening assays that rely on differential metabolic activity between separate control and treated wells are incapable of capturing phenotypic response and could overstate efficacy for cells with high rates of proliferation. Consequently, over 95% of anticancer agents that show efficacy in preclinical studies, fail in clinical trials. Recently, patient-derived organoid (PDO) models have been utilized in developing platforms to predict clinical efficacy of preclinical formulations. If successful, such predictive ex vivo technologies could revolutionize cancer treatment by reducing cost and time-to-market for new, more effective therapeutics. Objective: Characterize a novel bioprinted organoid tumor (BOT) high-throughput screening ex vivo platform for drug response prediction (DRP) with known proteosome and survivn inhibitors in colorectal cancer. Methods: Bioink for 3D printing BOTs was prepared with HT-29 cells, an established NCI-60 human colorectal adenocarcinoma cell line with known sensitivity to proteosome and survivin inhibitors. Bioink was deposited layer-by-layer on multiple substrates, in various geometrical configurations, and cured in stages to allow cells and matrix to self-assemble with limited degrees of freedom. BOTs were screened 24h and 48h after printing with proteosome inhibitor Bortezomib and survivin inhibitor YM-155. BOTs were evaluated 48h and 72h after treatment using immunofluorescence live/dead assay. Morphological phenotypic changes resulting from treatment were also recorded. Results: Proteasome and survivin inhibitors have been reported to inhibit proliferation and induce cell death in colorectal cancer cells. A dose dependent response was observed for both agents in our novel BOT HTS thereby validating the platform. In addition, characteristic self-assembly of HT-29 cells was observed to be disrupted at effective doses and at certain concentrations below the effective dose. Traditional ATP assays are incapable of recording such phenotypic modulation. Further, a higher proliferation profile was observed in untreated BOTs suggesting that use of independent control wells in traditional assays could overstate efficacy of treatment. Conclusions: Functional high-throughput ex vivo DRP technologies have the potential to transform cancer treatment – from bench to bedside – along the drug discovery to market roadmap for much needed novel anticancer agents.
Real-world biomarker testing patterns among patients with metastatic colorectal cancer (mCRC) treated with later lines of therapy (LOT) in the United States (US) community oncology setting.
Authors: Katta Arvind , Barzi Afsaneh , Hocum Brian Thomas , Appukkutan Sreevalsa , Cosgrove David , Sruti Ila , Shi Junxin , Dai Wei , Patton Gregory A. , Babajanyan Svetlana , Bekaii-Saab Tanios S.
Published: January 2024

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Background: Testing for BRAF and KRAS/NRAS mutations, HER2 amplifications, and MSI/MMR status is a standard of care for all patients with mCRC. There are limited real-world (RW) data regarding biomarker testing patterns among robust patients who are candidates for multiple LOT. We evaluated biomarker testing patterns among patients treated in community oncology practices who initiated regorafenib (REGO) and/or trifluridine/tipiracil (FTD/TPI), predominantly in 3rd or later lines of therapy. Methods: A retrospective analysis utilizing electronic medical record data from The US Oncology Network examined adult patients with mCRC who initiated REGO and/or FTD/TPI between 09/01/2015 and 11/30/2022 with follow-up until 05/31/2023. The proportion of patients tested for various biomarkers was assessed. Results: A total of 2684 mCRC patients initiated REGO and/or FTD/TPI (including 895 pts receiving both) in any LOT during the study period. The mean age of patients at baseline was 62.9 years, of whom 54.9% were male, 1599 (59.6%) patients were White and 436 (16.2%) were underrepresented minorities (Black or Hispanic/Latino). Patients were most commonly tested for KRAS mutations (75.2%) and least commonly for HER2 amplifications (22.6%). Age, gender, and race/ethnicity characteristics were similar between treatment subgroups, with 29.6% of minority and 23.1% of white patients not undergoing KRAS testing. Types of biomarkers tested and proportion of patients tested are reported in the table below. Conclusions: About one quarter of patients who were sufficiently robust to receive aggressive therapy did not undergo testing for KRAS, the oldest standard of care biomarker in CRC. We observed disparities by race/ethnicity. We also observed a correlation between rates of testing and treatment intensity, with patients who received both REGO and FTD/TPI having a higher rate of testing than those who received only one of the treatments. Understanding the pitfalls in biomarker testing will help pave the way for appropriate and equitable access to cancer care. [Table: see text]