bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topical diclofenac in prevention of capecitabine associated HFS in patients with breast cancer: An exploratory subgroup analysis of the D-ToRCH study.
Authors: Santhosh Akhil , Sharma Atul , Batra Atul , Gogia Ajay , Jha Akash , Pramanik Raja 
Published: August 2023

18 Background: Hand foot syndrome (HFS) is a dose-limiting side effect of capecitabine in patients with breast cancer. Celecoxib, an oral cyclo-oxygenase-2 (COX-2) inhibitor is effective in reducing the incidence of capecitabine associated HFS. However, it has not been adopted in the clinics due to concerns regarding cardiac and gastrointestinal toxicity. We report the efficacy of topical diclofenac in prevention of capecitabine associated HFS in patients with breast cancer. Methods: In the D-ToRCH (Diclofenac-topical for reduction of capecitabine related HFS) trial, we randomized 264 patients with breast or gastrointestinal cancers planned to receive capecitabine to apply either 1% topical diclofenac or placebo gel. Stratified (male or female; capecitabine monotherapy or combination therapy), permuted variable size block randomization was done using a computer-generated random numbers sequence. The primary objective was to compare the incidence of grade 2 or higher HFS in diclofenac and placebo arms. Secondary objectives were incidence of any grade HFS, capecitabine dose reductions due to HFS and self-reported adherence with application. Here, we report the exploratory subgroup analysis of patients with breast cancer. Results: The breast cancer subgroup included 148 patients (77 in drug arm and 71 in placebo arm). Baseline characteristics were similar in both arms. Median age of overall population was 47 years (IQR 39-56). 89 patients (60.1%) had an ECOG (Eastern Co-operative Oncology Group) performance status of 0-1, while the rest had a score of 2. Hypothyroidism was the most common comorbidity (n=24, 16.2%). Majority received capecitabine monotherapy (n=95, 64.2%). The most common additional chemotherapy drug used was lapatinib (n=42, 79.3%). 60 patients had stage 3 disease (40.8%) and 88 patients had metastatic breast cancer (59.5%). Overall, 20 patients developed any grade HFS, of which 6 were in the diclofenac arm and 14 in placebo arm (7.8% vs 19.7%, p=0.034). Grade 2/3 HFS events were noted in 3 patients (3.9%) in diclofenac arm and 11 patients (15.5%) in placebo arm (p=0.016). Capecitabine dose reductions were less frequent in the diclofenac arm compared to placebo (3.9% vs 15.5%). Adherence to topical treatment was similar in both the study arm. Other adverse events of capecitabine like diarrhea, mucositis and myelosuppression were similar in both the arms. Conclusions: Topical diclofenac gel significantly reduced the incidence of all grades of HFS in breast cancer patients receiving capecitabine. Applying topical diclofenac led to less frequent capecitabine dose reductions. Moving forward, we feel this should be the new standard of care and use of topical diclofenac should be regularized in medical oncology outpatient departments. Clinical trial information: CTRI/2021/01/030592 .
Efficacy of PD-1 inhibitors in the treatment of advanced gastrointestinal tumors and the effect on T-lymphocyte subsets and IL-6 levels in patients.
Authors: He XinCheng , Hou Lei , Bai Jun , Sun Chao , Wang Dongjie , He Jinyao , He Li , An Gaili 
Published: August 2023

44 Background: Immune checkpoint inhibitors (ICIs) have improved the therapeutic prospects in advanced gastrointestinal tumors. The PD-L1 expression has become one of predictive biomarkers for immunotherapy and used in treatment, but there are still some drawbacks. The aim of this study was to investigate the changes in peripheral blood T-lymphocyte subsets, IL-6 levels before and after treatment with ICIs and clinical significance. Methods: 70 patients with advanced gastrointestinal tumors who were hospitalized in Shaanxi Provincial People's Hospital from January 2020 to December 2022 were selected. 30 healthy patients were selected as controls. PD-L1 was detected by immunohistochemistry. Patients were treated with ICIs (sintilimab or pembrolizumab). 1 day before treatment, 20 days after the end of the 4 cycles of treatment, peripheral venous blood was collected and CT or MRI was performed to evaluate the therapeutic effect. Complete response (CR), partial response (PR), and stable disease (SD) were classified as immune response group, and progressive disease (PD) was classified as immune non-response group. To evaluate the effects of ICIs on the levels of T-lymphocyte subsets (Percentage of CD3+T cells, percentage of CD4+T cells, percentage of CD8+T cells, CD4+/CD8+, CD3+T cells, CD4+T cells, CD8+T cells) and IL-6. Results: Compared to controls, CD3+T cells, CD4+T cells, CD8+T cells and CD4+/CD8+ were significantly lower ( P<0.05). After 4 cycles of immunotherapy, the CD3+T cells, CD4+T cells, CD8+T cells, and CD4+/CD8+ levels were significantly higher ( P<0.05), and IL-6 levels were lower ( P<0.05). After 4 cycles of treatment, 48 cases were divided in the immune response group and 22 cases in the immune non-response group, with a treatment efficiency of 68.6%. In the immune response group compared to the immune non-response group, the levels of percentage of CD4+T cells, CD4+/CD8+, CD3+T cells and CD4+T cells were significantly higher ( P<0.05), while the percentage of CD8+T cells level was lower ( P<0.05). The percentage of CD4+T cells, CD4+/CD8+, CD3+T cells, CD4+T cells and CD8+T cells were significantly higher ( P<0.05) in the immune response group after 4 cycles of immunotherapy, while the percentage of CD8+T cells level was lower ( P<0.05) compared to before immunotherapy. The percentage of CD4+T cells and CD4+/CD8+ were significantly lower ( P<0.05), the percentage of CD8+T cells and CD8+T cells were higher ( P<0.05) in the immune non-response group compared to before immunotherapy. In the immune response group, the percentage of CD4+T cells was higher in the PD-L1 high expression groups (≥ 50%) compared to the PD-L1 low expression groups (< 50%) ( P<0.05). Conclusions: PD-1 inhibitors can affect the distribution of immune cells such as T-lymphocyte subsets in patients with advanced gastrointestinal tumors and improve the immune status of patients.
Progression free survival in patients of HCC on atezolizumab/bevacizumab in Pakistan.
Authors: Zafar Amjad , Niazi Zeeshan Ahmed Khan , Abdul Rashid Asma , Shakeel Nimra , Naqi Naeem , Aziz Zeba 
Published: August 2023

46 Background: Liver cancers had been the second leading cause of cancer related deaths, globally and hepatocellular carcinoma (HCC) accounts for 75-85% of the primary liver malignancies. Recently, the combination of Atezolizumab-Bevacizumab (atezo-beva) had been considered to be the standard of care for unresectable HCC. This study aims to assess the impact of the atezo-beva combination therapy on patients with HCC in Pakistan that will help to improve the standard of care and could lead to better health outcomes for our patients. Methods: A retrospective, uni-center study was conducted among the patients of HCC presented in the oncology department of Hameed Latif Hospital, Lahore, Pakistan, with the sample size of 46. The diagnosed patients of unresectable HCC were included. The combination of Atezolizumab 1200mg and Bevacizumab 15mg per kg were administered intravenous every 3 weekly. The therapeutic response to treatment was assessed by CT or MRI after 3 months of initiation of treatment as per Response Evaluation Criteria in Solid Tumors for immunotherapy (iRECIST). Results: A total of 46 participants were included with the median age of 61.5 years. 91.3% and 8.7% participants were male and female, respectively. Majority, 78.3% had viral etiology for HCC and the median level of alpha fetoprotein (AFP) was 99.43 ng/ml. The response to atezo-beva combination after 4 cycles of treatment was partial response (45.17%), progressive disease (15.2%), and stable disease (10.9%). Moreover, the current status of the participants was as ongoing treatment (67.4%), progressive disease (13.0%), drug side effects (6.5%), lost to follow up (6.5%) and mortality (6.5%). Conclusions: The effect of atezo-beva combination on unresectable HCC showed the majority to have partial response. However further studies are needed to validate these findings as well as to assess the PFS and OS of atezo-beva combination in Pakistani population.
Correlation of carbohydrate antigen 19-9 response with radiologic response and survival in intrahepatic cholangiocarcinoma: A prospective cohort study.
Authors: Wu Lu 
Published: August 2023

51 Background: Although Carbohydrate antigen 19-9 (CA19-9) showed promising prognostic value in patients with intrahepatic cholangiocarcinoma (iCCA), its role in response assessment remains unknown. We aimed to study the association of CA19-9 response (defined as > 50% reduction from baseline) with radiologic response, and its role in predicting outcome in patients with unresectable iCCA. Methods: A prospective cohort of 422 patients who were initially identified as unresectable iCCAs with baseline CA19-9 ≥ 100 U/mL and treated with systemic therapies at our institution between January 2017 and December 2021 was enrolled in this study. Radiologic response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. A landmark assessment of CA19-9 response and radiologic response was made. The association between CA19-9 response and imaging response, progression-free survival (PFS), or overall survival (OS) were analyzed, respectively. Results: Two hundred and sixty-seven (63.3%) patients showed CA19-9 response. CA19-9 response was seen in 93.2% (123/132) of radiologic responders, and 49.7% (144/290) of radiologic non-responders, respectively (P < 0.001). CA19-9 responders outperformed non-responders in median PFS (10.6 vs 3.6 months, P < 0.001) or OS (21.4 vs 6.3 months, P < 0.001), respectively. The common independent predictors of both OS and PFS included distant metastasis, CA19-9 non-responder, and radiologic non-responder in multivariable analysis. Conclusions: CA19-9 response is a valuable addition to assess tumor response and associated with improved outcome of iCCAs. Achieving CA19-9 response should be one of the therapeutic aims of patients with iCCA who are managed with systemic therapies. The results of this study have first published online in Cancer 2023 Jul 14. doi: 10.1002/cncr.34854 .
The safety of robot-assisted surgery versus laparoscopic surgery for rectal tumor patients.
Authors: Tajima Jesse Yu , Yokoi Ryoma , Kiyama Shigeru , Hayashi Hirokata , Higashi Toshiya , Asai Ryuichi , Tanaka Yoshihiro , Okumura Naoki , Murase Katsutoshi , Matsuhashi Nobuhisa 
Published: August 2023

56 Background: Robotic assisted surgery for the rectum has dramatic increased. In addition to the magnifying effect of laparoscopic benefit, robot-assisted surgery has multi-joint function and 3D vision which allows more precise manipulation in the deep pelvic region and is thought to contribute significantly to perioperative safety. However, the superiority of robotic-assisted surgery still remains controversial. In this study, we compared the short-term results of laparoscopic and robotic-assisted surgery for rectal tumors. Methods: This study was a single-center, retrospective study. We included 273 rectal tumor patients who underwent surgery with anastomosis from 2017 to 2021. 169 patients underwent laparoscopic surgery (Lap group) and 104 patients underwent robotic-assisted surgery (Robot group). Postoperative complications were compared by matching using the propensity score based on the IPTW method with the maximum tumor diameter, cT, and cN stage as adjustment factors (SMD≤0.2 was defined as no difference between the groups). Results: Among the patient backgrounds, blood loss, LPLN dissection and tumor diameter showed significant difference. Moreover, rate of cT3-4, cN positive were significantly high in the Lap group. The rate of postoperative complications based on clavien-dindo classification (Lap group vs Robot group), grade II or higher in 29.6% vs 19.2%, grade III or higher in 11.2% vs 5.8% and anastomotic leakage (all grade) in 5.9% vs 4.8%. Adjusted by propensity score matching for all the factors of SMD≤0.2, though there was no significant difference in anastomotic leakage (OR 0.76, 95%CI 0.46-1.27, p=0.296), both postoperative complications of grade II or higher (OR 0.66, 95%CI 0.50-0.87, p=0.004) and grade III or higher (OR 0.29, 95%CI 0.16-0.53, p<0.001) were significantly lower in the Robot group. Conclusions: The results of this study showed better short-term outcomes which suggest that robotic-assisted surgery for rectal tumor is superior in safety than laparoscopic surgery.
Predicting response of gemcitabine plus cisplatin chemotherapy using RNA sequencing in patients with advanced urothelial carcinoma.
Authors: Park Kwonoh , Hong Yun Jeong 
Published: August 2023

66 Background: Despite of advancement using new agents including ICIs in treatment of urothelial carcinoma (UC), cisplatin-based chemotherapy is still standard of care in both 1st line palliative setting and perioperative setting. Previous studies regarding response prediction of cisplatin-based chemotherapy are limited in selecting target molecule or gene, there have been no comprehensive study for whole genome information. This study aimed to identify key genes to predict response of gemcitabine plus cisplatin (GC) in advanced UC by mRNA sequencing (RNA-seq). Methods: Between JAN 2016 and DEC 2019, advanced UC patients treated with GC and underwent response evaluation were enrolled. Patients were divided into the responder group (CR or PR) and non-responder group (SD or PD). RNA was extracted from the formalin fixed embedded tissue (FFED) and RNA-seq was performed on the Illumina RNA-seq platform. Differentially expressed genes (DEGs) were identified between responder group and non-responder group. Marker selection was performed as following steps: (1) DESeq2 (Adjusted P-value < 0.1) and Mann-Whitney U test (P-value < 0.05), (2) random forest (RF) and logistic regression, and (3) assessments for relevant markers by analyzing RNA/Protein expression level, survival information, and antibody staining results using ProteinAtlas. Results: Twenty-nine patients received GC chemotherapy during study period. Among them, 10 patients who had available FFED specimens and clear response evaluation were enrolled and performed RNA-seq. Median age was 65.5 years (range, 62-76), and all were male. They were grouped of 7 patients in responder and 3 patients in non-responder. Among 13,773 genes based on RNAseq, we identified 37 DEGs candidate (Step 1), followed by 22 DEGs selected (Step 2), and finally 9 DEGs were identified (Step 3). Among the 9 DEGs, 3 genes (UPK2, PCGF3, and POFUT1) were consistently expressed with survival data of TCGA, the expression of 3 (ITGA3, HSPA1B, GSTM3) was the opposite of that of TCGA, and the remaining 3 genes (S100A2, TDRP, and RPS6KA2) were not relevant. Conclusions: We found 3 key genes (UPK2, PCGF3, and POFUT1) that related with favorable response of GC in our advanced UC cohort which were confirmed in TCGA data. Our study results should be further investigated in an expansion cohort using immunohistochemistry staining matched with key genes for convenient practical application.
Effect of low FGFR3 but high CD8 T cell infiltrated immune micro-environment on treatment response with pembrolizumab in upper tract urothelial carcinoma.
Authors: Shigeta Keisuke , Matsumoto Kazuhiro , Yasumizu Yota , Tanaka Nobuyuki , Takeda Toshikazu , Kosaka Takeo , Morita Shinya , Mizuno Ryuichi , Asanuma Hiroshi , Hara Satoshi , Oya Mototsugu 
Published: August 2023

69 Background: Although several evidence revealed that upper tract urothelial carcinoma (UTUC) with fibroblast growth factor receptor 3 (FGFR3) mutations and/or expressions follow favorable outcomes, the relationship between immune cell markers and FGFR3 expression remains unknown. We aimed to clarify FGFR3 based immune microenvironment and to investigate biomarkers to predict treatment response of Pembrolizumab (Pem) in UTUC patients. Methods: We conducted immunohistochemical (IHC) staining of 214 UTUC patients. FGFR3, CD4, CD8, CD68, CD163, CD204, and PDL-1 expressions were examined and we created immune clusters assessed with heatmap clustering. We assessed the relationships of these immune markers toward further prognosis. In addition, neutrophil-lymphocyte ratio (NLR) and absolute monocyte count (AMC) were evaluated as blodd markers for predicting treatment response from Pem. Results: Among the UTUC patients, 109 (50.9%) showed high FGFR3 expression, and showed favorable prognosis compared to the counterparts. Among the six immune markers, CD8 high expression was revealed as an independent favorable factor (HR=0.44) whereas CD204 high was shown as one of independent prognostic factors for cancer death (HR=1.80). From the FGFFR3 based immune clustering, three immune clusters were identified in UTUC tumor specimen. Cluster A showed FGFR3 low with TAM rich component (CD163 and CD204 high) followed with poor prognosis due to poor response to Pem. Cluster B showed FGFR3 low with immune hot component (CD8 high) followed with most favorable prognosis due to good response to Pembrolizumab. Cluster C showed high FGFR3 expression but immune cold component, followed with favorable prognosis due to FGFR3 high expression but poor response was confirmed with Pem. Regarding of blood biomarkers, NLR showed correlation with CD8 expressions while AMC showed correlation with CD204 expressions. By using validation cohort (n=138), NLR<3.3 showed significantly longer survival compared to the counterparts with Pem treatment (p=0.046). Conclusions: The present study demonstrated a unique immune profile found in UTUC patients. Although most of the patients show poor response to Pem, low FGFR3 expression with immune-hot status may receive clinical benefit from Pem treatment.
The need for re-staging transurethral resection of bladder tumour (ReTURBT) in Ta high grade and T1 tumours: Questioning the norms—Inferences from a national institute.
Authors: Ram Prasanna , Nayak Prasant , Das Manoj Kumar , Mandal Swarnendu , Tripathy Sambit , Barik Kalandi , Gorrepati Rohith , Gaur Abhay , Kumar Dheeraj , Tarigopula Vivek , Sahoo Suman , Singh Kirti , Chundampetta Sabique , Ambade Saharsh 
Published: August 2023

79 Background: The incidence of urinary bladder carcinoma is increasing at an alarming rate. Non-Muscle Invasive Bladder Cancer (NMIBC) accounts for seventy percent of these patients. Current guidelines recommend a Restage Transurethral Resection of Bladder Tumour (ReTURBT) for Ta high-grade and all T1 non-muscle invasive tumours, to increase the accuracy of staging. The question of whether a second surgery is always necessary remains unanswered. Here, the patient's concern about the completeness of the procedure, perioperative morbidity, and the financial burden involved in a major surgery cannot be ignored. Moreover, it also puts a strain on the already overburdened healthcare systems in developing countries like India. Trying to answer this question of whether it is oncologically sound to omit a second resection, our study evaluated the outcomes of patients undergoing restage TURBT with regards to the rate of upstaging, upgrading and residual tumours in these patients. Methods: The study was a retrospective analysis of a prospectively maintained database including NMIBC patients from September 2019 to February 2023. A total of 112 patients underwent restage TURBT. Their demographic details, imaging, cystoscopy findings, and histopathological data were recorded. The primary objective was to analyse the rate of upstaging, while the secondary objectives were to look at the residual tumour and upgrading rates in these patients. Results: Out of 112 patients (T1- 71 & Ta high grade- 41), 24 patients (21.42%) had residual tumours at restage (T1- 20 & Ta high grade- 4) while 21 (18.75%) patients (T1- 19 & Ta high grade- 02) were upstaged to T1 or T2. Grade progression was seen in 15.41 % T1 patients, while none of the Ta high grade patients had a change in grade. Deep muscle in the initial resection was present in 87.5 % of the specimens. Conclusions: Our retrospective analysis points towards skipping a restage TURBT in select Ta patients in whom a well-performed and adequate initial TURBT was done. Further prospective studies with large patient cohorts are needed to confirm and reinforce these proposed facts.
Cardiopulmonary exercise testing of patients with metastatic castrate-resistant prostate cancer as screening for vigorous exercise medicine prescription.
Authors: Newton Robert Usher , Hart Nicolas H. , Kenfield Stacey A. , Galvao Daniel Abido , Courneya Kerry S. , Ryan Charles M , Chan June M. , Catto James W.F. , Winters-Stone Kerri M. , Van Hemelrijck Mieke , Wylie Harriet , Schumann Moritz , Skinner Tina , Praet Stephan , Saad Fred 
Published: August 2023

80 Background: Exercise is recommended for patients with prostate cancer to manage treatment adverse effects, improve quality of life and potentially influence cancer-specific outcomes. Men with advanced prostate cancer and metastatic disease may be at increased risk of cardiac events due to their cancer treatment and comorbidities. The aim of this study was to assess the safety and efficacy of cardiopulmonary exercise testing (CPET) for assessing cardiorespiratory capacity and risk screening of patients with metastatic castrate-resistant prostate cancer (mCRPC) prior to engaging in a vigorous program of exercise medicine. Methods: Experimental design was a cross-sectional analysis of screening CPET’s from a Phase III Randomised Controlled Trial (INTERVAL-GAP4) within the clinical setting involving men with mCRPC. Testing incorporated medically supervised, symptom limited, CPET with electrocardiogram (ECG) performed on a cycle ergometer until volitional exhaustion or maximal oxygen uptake peak (V02.PEAK) attained. Outcome Measurements included safety (incidence and severity of adverse events), feasibility (completion of CPET) and efficacy (performance outcomes, screen-fails, and cardiac pathology). Descriptive statistics were calculated as mean and standard deviation. Results: 104 men (age 71.5 ± 8.4 years) with mCRPC completed a medically supervised CPET. Of these, 96 patients (92.3%) met the criterion for V02.PEAK attainment and were randomised to the INTERVAL-GAP4 trial, with 8 (7.7%) CPET screen-fails. Four positive cardiac abnormalities (3.8%) were observed, with these patients referred to a cardiologist for further assessment. Referred patients were all cleared to participate in vigorous exercise with no clinically significant cardiovascular disease or were determined to have newly diagnosed and subsequently controlled cardiovascular disease. Average V02.PEAK was 1.72 ± 0.51 L.min-1 absolute and 18.96 ± 5.30 mL.kg-1.min-1 relative which is in the 10-15th percentile for healthy men of this age. Maximal heart rate achieved was 141 ± 20 bpm at a maximal workload of 128 ± 40 W. There were no cardiac events or any other exercise-related adverse events during the testing. Conclusions: Maximal CPET is safe for men with advanced prostate cancer. CPET with ECG is also an effective cardiac stress screening tool prior to engaging in a vigorous exercise medicine program to detect underlying cardiovascular health issues. Further, results from CPET can be used to inform appropriate exercise prescription individualised to the patient. Clinical trial information: NCT02730338 .