bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing clinical outcomes between PD-1 and PD-L1 inhibitors plus bevacizumab combined with hepatic arterial interventional therapies in unresectable hepatocellular carcinoma: A single-center real-world study.
Authors: Pan Yangxun , Yuan Ze , Hu Dandan , Chen Minshan , Zhang Yaojun
Published: July 2024

e16229

Background: Systemic therapies combined with locoregional therapies were considered a potent therapeutic strategy in treating patients with unresectable hepatocellular carcinoma (uHCC). Given the A+T strategy became the first-line treatment for advanced HCC patients, the roles of programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitors in the combination therapies for treating patients with uHCC needed to be further discussed. The current study compared the clinical outcomes between PD-1 and PD-L1 inhibitors plus bevacizumab combined with hepatic arterial interventional therapies (HAIT) among patients with uHCC. Methods: From October 2019 to May 2023, 142 uHCC patients were retrospectively analyzed in Sun Yat-sen University Cancer Center, including 73 or 69 patients treated with either PD-1 (PD-1 group) or PD-L1 (PD-L1 group) inhibitors, respectively, combined with HAIT plus bevacizumab. The progression-free survival (PFS) and tumor responses were analyzed per mRECIST. Results: At the data cut-off, the median PFS was 5.5 months (95% CI 5.3-7.1 months) in the PD-1 group and 7.5 months (95% CI 7.0-9.6 months) in the PD-L1 group, respectively ( P=0.280; HR=0.74; 95%CI 0.43-1.28). The PD-L1 group showed a significantly better median intrahepatic PFS (8.1 months, 95%CI 7.6-10.2 months) than the PD-1 group (6.5 months, 95%CI 6.2-9.0 months; P=0.014; HR=0.35; 95%CI 0.16-0.81). The overall response rate (ORR; 49.3% vs. 66.7%, P=0.054), intrahepatic control rates (53.4% vs. 69.6%, P=0.070) and overall disease control rate (DCR; 68.5% vs. 78.3%, P=0.261) showed no significant difference in both groups, while the PD-L1 group demonstrated significantly higher intrahepatic disease control rate than the PD-1 group (76.7% vs. 92.6%, P=0.016). Conclusions: PD-1 and PD-L1 plus bevacizumab combined HAIT shared similar PFS, DCRs, and ORRs in treating uHCC patients. The PD-L1 plus bevacizumab combined with HAIT demonstrated a better intrahepatic control than those of PD-1, which needed further validation at a higher evidence level.
Intervention to improve care delivery and patient self-management for people with primary liver cancer who have socioeconomic disadvantages.
Authors: Weldon Christine B. , Mizrahi Jonathan , Therapondos George , Du Lingling , Palmer Carol , Medina Amanda , Sandow Tyler , Gimenez Juan , Cohen Ari , O'Brien Michelle , Ogale Sarika , Tan Amie , Trosman Julia R.
Published: July 2024

e16232

Background: The 4R Oncology Model (4R = Right information/care/patient/time) supports patient self-management (Trosman, JCOOP 2021) and guideline-based care delivery (Liu, JCOOP 2022). 4R Care Sequence plans provide a care checklist and a graphical depiction of care timing and sequence. Here we report the impact of the 4R Care Sequence plans on care delivery and patient self-management among patients with primary liver cancer with socioeconomic disadvantages. Methods: 4R plans were provided to patients with liver cancer Jan – Dec ’23 (4R cohort). Patient-reported data were collected via surveys. Analyses compared the 4R cohort (N = 42) to a control cohort of patients who received care pre-4R, Jan - Dec ’22 (N = 52). Statistical analysis used Fisher’s exact and t-tests. Results: Survey response rates: control cohort 61% (52/85), 4R cohort 58% (42/73). Comparing control to 4R cohort respectively, patients exhibited the following characteristics: male (63%, 67%), White (67%, 74%), Black (25%, 19%), an average age (64.1, 63.9), and the majority had annual income less than $30,000 (62%, 67%). 4R significantly improved care delivery and patient self-management in all metrics vs control (Table). Patient rating of provider satisfaction on a 10-point scale was lower in the control cohort compared to the 4R cohort (8.4, 9.8, p < 0.0001), data not shown. The significant improvement across metrics was observed regardless of age, race, sex. Among patients who made < $30k annually, referral rates to a dentist before treatment increased significantly between control and 4R cohorts (19%,79%, p < 0.0001). Among patients who made > $30k annually, dental referral rates did not change between the control and 4R cohorts (70%, 71%, p = 1.00). Income was not a factor for other metrics. Conclusions: The 4R intervention using Care Sequence plans for patients with primary liver cancer facilitated improvements in care delivery and patient self-management regardless of age, race, sex or income. Our results indicate that 4R benefits all patients, including those with socioeconomic disadvantages. [Table: see text]
Durvalumab plus gemcitabine/cisplatin/nab-paclitaxel in resectable biliary tract cancer: A phase II, single-arm, open-label study (DurGAP).
Authors: Li Rentao , Liu Yang , Liu Yayue , Fu Linlin , Qi Qi , Zhang Xihao , Cui Yunlong , Lu Wei , Li Huikai
Published: July 2024

e16260

Background: Biliary tract cancer (BTC) presents a formidable challenge, marked by its aggressive nature and dismal prognosis. While surgical resection remains the lone potentially curative option, 5-year survival rates have plateaued below 50%, largely due to high rates of recurrences and metastases. Given these sobering statistics, the imperative for neoadjuvant therapy to enhance outcomes is evident. Building upon the success of the TOPAZ-1 trial, which established durvalumab in combination with gemcitabine and cisplatin as a standard regimen for advanced BTC, this study seeks to assess the safety and efficacy of incorporating neoadjuvant durvalumab alongside gemcitabine, cisplatin, and Nab-paclitaxel for resectable BTC. Methods: Resectable, treatment-naïve BTC patients (pts) were enrolled and administered 3 cycles of neoadjuvant durvalumab (1000mg, iv, d1, q3w) + GAP (gemcitabine 1000mg/m2, cisplatin 25mg/m2, Nab-paclitaxel 100mg/m2, d1, d8, 21d cycle). Primary endpoints included assessing Adverse Events (AEs) and Objective Response Rate (ORR). Secondary endpoints comprised R0 resection rate, Recurrence-Free Survival (RFS), Overall Survival (OS). Results: Between Feb, 2023 to Jan, 2024, a total of 24 patients were enrolled, 12 (50.0%) were male, all with ECOG 0 and 18 (75.0%) presenting with N1 status. Median age: 65 years. Primary sites: intrahepatic (50.0%), extrahepatic (33.3%), gallbladder (16.7%). Median follow-up: 8.75 months; all pts received ≥2 neoadjuvant cycles. The ORR was 62.5%, with all 15 pts demonstrating partial responses (PR). The DCR was 87.5% with 15 PR and 6 stable disease (SD) responses. The most common treatment-related adverse events (TRAEs) were increased ALT/AST (28.6%), anemia (21.8%), hypoalbuminemia (16.0%). Grade ≥3 TRAEs occurred in 2 (8.3%) pts. 13 pts underwent resection, achieving R0 resection in 12 (92.3%) of cases, comprising 10 PR, 2 SD, and 1 pt deemed eligible for surgery post-assessment despite a PD response. 11 pts did not undergo resection, with reasons including patient refusal (4 PR, 1 SD), not meeting resection criteria (2 PD), lost to follow-up (1 PR, 1 SD), and still under active follow-up (2 SD). Conclusions: Neoadjuvant durvalumab combined with gemcitabine/cisplatin/Nab-paclitaxel demonstrated a promising ORR and DCR, with a tolerable safety profile, warranting further investigations in a larger cohort. Clinical trial information: NCT05640791 .
Preoperative BMI and long-term survival in NAFLD-associated hepatocellular carcinoma: A multicenter study revealing a paradox.
Authors: Zhang Wei , Li Zi-Qiang , Diao Yong-Kang , Liu Xing-Kai , Guo Hong-Wei , Wu Xiao-Chang , Wang Hong , Wang Si-Yuan , Zhou Ya-Hao , Lu Jun , Gu Wei-Min , Chen Ting-Hao , Li Jie , Liang Ying-Jian , Wang Ming-Da , Chen Zhong , Lv Guo-Yue , Yang Tian
Published: July 2024

e16262

Background: As non-alcoholic fatty liver disease (NAFLD) emerges as a key factor in hepatocellular carcinoma (HCC) development, exacerbated by the global obesity epidemic, the prognostic role of body mass index (BMI) in NAFLD-HCC patients undergoing surgical resection remains unclear. This study aims to elucidate the impact of preoperative BMI on long-term outcomes after hepatectomy in patients with NAFLD-HCC, offering insights for more personalized treatment strategies. Methods: In this multicenter retrospective study, patients with early-stage (BCLC stage 0/A) NAFLD-HCC who underwent curative hepatectomy between 2009 and 2022 were analyzed. Based on preoperative BMI, patients were classified into lean ( < 23.0 kg/m2), overweight (23.0-27.4 kg/m2), and obese (≥ 27.5 kg/m2) categories. The primary endpoints, overall survival (OS) and recurrence-free survival (RFS), were compared across these BMI groups. Results: This large multicenter cohort comprised 309 early-stage NAFLD-HCC patients: 66 lean, 176 overweight, and 67 obese. Liver-, tumor-, and surgery-related characteristics were similar across groups. Lean patients exhibited significantly lower 5-year OS and RFS (55.4% and 35.1%, respectively) compared to overweight patients (71.3% and 55.6%, P = 0.017 and P = 0.002), with outcomes comparable to obese patients (48.5% and 38.2%, P = 0.939 and P = 0.442). Multivariable Cox-regression analysis revealed lean BMI, but not obese BMI, as an independent predictor of decreased OS (HR: 1.69; 95%CI: 1.06-2.71; P = 0.029) and RFS (HR: 1.72; 95% CI: 1.17-2.52; P = 0.006). Conclusions: This study challenges conventional perceptions of BMI in cancer prognosis, revealing that lean NAFLD-HCC patients have poorer long-term surgical outcomes compared to their overweight and obese counterparts. These findings underscore the need for a nuanced understanding of BMI’s role in NAFLD-HCC management and prompt further investigation into the underlying biological mechanisms of this paradox.
Survival outcomes in patients with non-metastatic intrahepatic cholangiocarcinoma in United States: A nationwide analysis.
Authors: Mohsin Aleenah , Ahmad Shahzaib , Khan Hadin Darain , Aziz Nouman , Naeem Hamza , Bellur Shreyas S. , Ganiyani Mohammad Arfat , Jayram Diya , Ahluwalia Manmeet Singh
Published: July 2024

e16277

Background: Intrahepatic cholangiocarcinoma (ICC) is one of the most aggressive primary liver malignancies contributing to notable morbidity and mortality. Surgical resection (Sx) is the mainstay of treatment for non-metastatic ICC. However, it is unclear if augmenting resection with chemotherapy (CT), radiotherapy (RT) or chemoradiation (CRT) confers survival benefit in non-metastatic ICC. This study aims to assess effective therapeutic option for non-metastatic ICC. Methods: We queried the National Cancer Database to identify patients diagnosed with non-metastatic (stage 0-3, M0) ICC between 2004 and 2020. We reported survival outcomes in the study cohort in concordance with STROBE guidelines. We analyzed median overall survival (mOS) and differences in survival using the Kaplan-Meier (KM) methodology and pair-wise log-rank test, respectively in 6 groups based on treatment: Sx, CT, RT, Sx+CT, Sx+CRT, and CRT. Results: The analysis included 20,005 patients diagnosed with non-metastatic ICC with a median age of 66 years (range: 15-90+ years). The population included White (83.6%), Black (8.3%), and Asian (3.9%). 50% of the patients were male, 91.9% were non-Hispanic, 88.8% had Charlson-Deyo score (CDS) of 0-1, 11.2% had CDS ≥2, 51.6% were treated at academic/tertiary care program. 24.0% of the cases had positive lymph nodes. 3,394 patients (23.9%) of the total patients underwent Sx, 4,313 (30.4%) patients underwent CT alone, 1,023 (7.2%) patients underwent RT, 2753 (19.3%) patients underwent Sx+CT, 1100 (7.7%) patients underwent Sx+CRT, and 1629 (11.5%) patients underwent CRT alone. Patients who underwent Sx alone had better mOS (46.3 months, 95% CI 42.8-48.9) than all other modalities, including Sx+CT (46.0 months, 95% CI 43.9-48.0, P = 0.10), Sx+CRT (44.5 months, 95% CI 35.6-50.4, P = 0.11), CT (12.4 months, 95% CI 11.9-12.8, P < 0.01), RT (18.3 months, 95% CI 16.3-19.8, P < 0.01), and CRT (18.1 months, 95% CI 17.0-19.4, P < 0.01). Conclusions: Our study indicates that surgical resection yields the best survival outcomes when compared to other treatment modalities for nonmetastatic ICC. However, there is no significant difference in survival when surgery is combined with chemotherapy or chemoradiation in nonmetastatic ICC. Further prospective research is needed to refine treatment strategies and enhance outcomes for ICC patients. [Table: see text]
Survival outcomes associated with treatment modalities in stage 4 gallbladder neuroendocrine tumors: A nationwide analysis.
Authors: Aziz Nouman , Ahmad Shahzaib , Ganiyani Mohammad Arfat , Ozair Ahmad , Sarwar Muhammad Zeeshan , Jayram Diya , Khan Hadin Darain , Ahluwalia Manmeet Singh
Published: July 2024

e16295

Background: Gallbladder neuroendocrine tumors (GNETs) are rare, heterogeneous, and aggressive tumors of the gallbladder. GNETs usually present in the elderly ( > 60 years) and there are no clear clinical guidelines to treat stage 4 GNETs due to rarity. We evaluated therapeutic options for stage 4 GNETs. Methods: We included stage 4 GNETs diagnosed between 2004-2020 in the National Cancer Database. Treatment was stratified into combination therapy (Comb) - surgery (Sx) and chemotherapy (CT), Sx alone and CT alone. Survival outcomes were expressed as Kaplan-Meier curves and Cox proportional hazard model adjusting for age, Charlson-Deyo score (CDS) and sociodemographic variables like sex, race, ethnicity, insurance status, and facility location. We expressed survival outcomes as median overall survival (mOS, 95% CI) and time-dependent survival as hazard ratio (HR, 95% CI). Results: Of 242 patients with stage 4 GNETs, the median age was 64 years (range 29-90+ years), 62.4% were female, 66.9% had CDS of 0, 22.4% had CDS of 1, 10.8% had CDS ≥2, 98.7% had poorly differentiated tumor (grade 3 or 4), 70.3% were White, 85.9% were non-Hispanic, median size of the primary tumor was 10.7 cm (range 0.8-14.1 cm) and 47.8% were treated at academic or research program. 46 (19.0%) patients received Comb, 171 (70.7%) received CT and 25 (10.3%) patients received Sx alone. The mOS was 11.5 months (9.3-18.4), 9.4 months (7.9-11.2), 4.2 months (2.3-6.3) for Comb, CT and Sx, respectively (P < 0.001). Pairwise log-rank revealed no significant differences between Comb and CT groups (P = 0.07). In univariate Cox analysis, CDS ≥2 showed HR of 1.6 (1.0-2.4; p = 0.04), Sx showed HR of 1.7 (1.1-2.7; P = 0.02), and Medicare had HR of 1.35 (1.02-1.78; p = 0.037). However, on multivariate analysis, uninsured patients (HR = 5.16; 95% CI 1.50-17.7; P = 0.009) and those receiving Sx alone (HR = 2.09; 95% CI 1.27-3.46; P = 0.004) had unfavorable outcomes. Conclusions: The combination of primary site surgery with CT improves survival in stage 4 GNETs as compared to resection alone. However, there is no significant difference in survival in combination therapy and CT. We emphasize the need for robust prospective studies comparing the efficacy of chemotherapy, neoadjuvant and adjuvant chemotherapy for stage 4 GNETs.[Table: see text]
Predictive value of baseline 68Ga-FAPI PET/CT in the first-line therapy of pancreatic ductal adenocarcinoma (PDAC).
Authors: Jia Ru , Hao Xin-Zhi , Si Hai-Yan , Zhu Wen-Jia , Wang Zhi-Kuan , Huo Li , Dai Guang-Hai
Published: July 2024

e16300

Background: This study aimed to explore whether parameters from the baseline 68Ga-fibroblast activating protein (FAP) inhibitor (FAPI) PET/CT could predict outcomes in PDAC patients receiving first-line treatment based on a Phase II clinical trial (previously reported in 2023 ASCO, abstr 4142 and 2024 ASCO-GI, abstr 671). Methods: Patients underwent 68Ga-FAPI PET/CT scan before the first dose of first-line treatment of NASCA (nab-paclitaxel, S-1, surufatinib, and camrelizumab) or GnP (nab-paclitaxel and gemcitabine) regimen were enrolled. The parameters of 68Ga-FAPI-04 PET/CT, including SUVmax, SUVmean, target-to-background ratio (TBR) (background including liver, muscle, and blood pool), and FAP expression tumor volume (FTV) of each tumor lesion, were recorded. The highest SUVmax, SUVmean and TBR (H-SUVmax, H-SUVmean, H-TBR), and summed FTV in each region (primary tumor, liver, peritoneal, lymph nodes, lung and bone) and whole body (WB) were also evaluated. Results: From January 2022 to July 2023, a total of 28 out of 42 patients were enrolled. Nineteen patients had received the NASCA regimen, and 9 patients had received GnP regimen. The SUVmax of primary site and metastatic sites were 16.46 (7.56-28.03) and 7.83 (2.13-19.22), respectively. The SUVmean of primary site and metastatic sites were 9.24 (4.05-14.99) and 4.63 (1.44-11.25), respectively. Both the SUVmax and SUVmean of primary site were significantly higher than that of metastatic sites (P < 0.001). 68Ga-FAPI PET/CT showed higher sensitivity in detecting metastases than CT/MRI, especially peritoneal metastases. Only 30% (3/10) of patients were diagnosed with peritoneal metastases by CT/MRI. The ROC curve and AUC for the H-SUVmax, H-SUVmean, and summed FTV in WB or each region were evaluated by separating patients into responders and non-responders. H-SUVmax-WB had the highest AUC for predicting treatment response with a cut-off value of 18.2. Patients with H-SUVmax-WB below 18.2 had significantly longer progeression-free survival (PFS) than those above [8.8 months vs 3.8 months, P = 0.026, HR = 0.30, 95%CI (0.10-0.87)]. However, H-SUVmax-WB was not a prognostic factor (P = 0.292). Among H-TBRblood, TBRmuscle and TBRliver, H-TBRblood-WB (25.9 as the cut-off) was the most pronounced predictive (P = 0.001) and prognostic factor (P = 0.039). The trend of differences in PFS continue exists both in NASCA (p = 0.047) and GnP group (p = 0.018). The multivariable analysis revealed that H-TBRblood-WB (P = 0.026) and liver meatastases (P = 0.026) were independent predictive factors. Conclusions: The highest TBRblood of tumor lesions on 68Ga-FAPI PET/CT was associated with poor response in first-line treatment of PDAC. The utility of 68Ga FAPI PET/CT before treatment could reflect the tumor burden and may predict the response of therapy. For those with high uptake of FAPI, therapy targeting FAP might have a promising future.
Exploring the association of smoking status with clinical outcomes in patients with mPDAC treated on a clinical trial of maintenance niraparib plus immune checkpoint blockade.
Authors: Rathore Srishti , Reiss Kim Anna , Teitelbaum Ursina R. , Chapin William Joseph
Published: July 2024

e16302

Background: Previous research has hinted at a positive association between smoking history and outcomes in non-small cell lung cancer patients being treated with immune checkpoint blockade (Wang L. et al., 2021)(Cortellini A. et al., 2021). The PARPVAX trial (NCT03404960) assessed the efficacy of maintenance niraparib plus either nivolumab (Arm A) or ipilimumab (Arm B) in platinum-sensitive patients with mPDAC (Reiss KA. et al., 2022). We investigated whether there was an association between patient smoking history and outcomes on this trial. Methods: Patients treated on NCT0340960 were categorized by smoking status (binary; never/any smoking history). We performed multivariable Cox proportional hazards models for PFS and OS with a pre-specified set of covariates that underwent negative backward selection until the ratio of events to degrees of freedom in the model was less than 10 to avoid overfitting. Models were also performed within each arm in an exploratory fashion to determine if differences were observed between treatment groups. Results: Overall, 42% (Arm A) and 58% (Arm B) of patients had any history of smoking. Any smoking history was significantly associated with improved OS in the multivariate model (HR = 0.45 [0.24 – 0.86]; P = 0.015). The multivariate PFS analysis demonstrated a 37% reduction in the hazard of progression or death, but the result was not statistically significant (HR = 0.63 [0.37 – 1.09]; P = 0.10). When separated by treatment arm, any smoking history had a significant association with PFS (HR = 0.32 [0.14 – 0.73]; P = 0.007) and OS (HR = 0.30 [0.11 – 0.80]; P = 0.016) in Arm B but not Arm A. Conclusions: Our ad hoc analysis of outcomes by smoking status in a population of patients with advanced PDAC undergoing experimental maintenance treatment with PARPi and ICB suggests that a smoking history may be associated with improved outcomes, particularly in patients who received anti-CTLA4 therapy. Sample size greatly limited adjustment for potential confounders and these results are hypothesis generating only. [Table: see text]
Exploring racial disparities and tumor characteristics of CA19-9 producer and non-producer among patients with advanced pancreatic ductal adenocarcinoma (PDAC): Implications for survival and personalized treatment strategies.
Authors: Omore Ibrahim , Gandhi Sonal , Wu Linda , Cohen Deirdre J.
Published: July 2024

e16309

Background: Despite substantial progress in cancer treatment, PDAC remains a highly lethal disease. CA19-9 plays a crucial role in PDAC diagnosis and therapeutic response assessment. We aimed to evaluate racial differences, tumor characteristics, and outcomes between CA19-9 non-producers and producers among advanced PDAC patients (pts) at an academic teaching hospital. Methods: A retrospective analysis was conducted in patients with unresectable or metastatic PDAC treated at Mount Sinai Health System between January 2012 and December 2021. Pts were categorized into two groups based on CA19-9 levels, using a threshold of 37 U/mL: CA19-9 non-producers (≤37 U/mL) and CA19-9 producers ( > 37 U/mL). Demographic and clinical data were compared between the two groups, and the association between CA19-9 levels and overall survival (OS) was assessed using Kaplan-Meier estimates and multivariable Cox proportional hazards regression models. Results: A total of 238 pts were included in the analysis, with a median age of 67 years and a balanced gender distribution (52% male). The cohort comprised locally advanced (29.8%) and metastatic (70.2%) cases, with a diverse ethnic composition including non-Hispanic whites (37%), non-Hispanic blacks (25%), and Hispanics (18%). Among the pts, 23.5% were CA19-9 non-producers, while 76.5% were CA19-9 producers. Significant racial differences were observed, with non-Hispanic blacks more likely to be CA19-9 non-producers compared to non-Hispanic whites ( P< 0.001). However, no statistically significant differences were found in age, smoking status, tumor location, size, or site of metastasis between the two groups. Median overall survival (OS) was 13m for CA19-9 producers and 16m for non-producers, but this difference was not statistically significant in both univariate and multivariate analyses (HR 1.09, 95% CI 0.74-1.58, P = 0.66; HR 1.06, 95% CI 0.72-1.58, P 0.8). Hispanic ethnicity was correlated with improved OS (HR 0.59, 95% CI 0.36-0.95, P = 0.029), while larger tumor size predicted worse OS (HR 1.17, P < 0.001). Conclusions: This study highlights racial disparities in CA19-9 production among locally advanced and metastatic PDAC patients. Despite observed differences, CA19-9 levels alone did not emerge as a statistically significant predictor of OS. Future research should delve deeper into the racial disparities observed in CA19-9 production, exploring underlying biological mechanisms and potential implications for diagnostic and therapeutic approaches as this could refine our understanding of PDAC, facilitating targeted interventions for improved patient outcomes.
Efficacy of platinum chemotherapy agents in adenosquamous carcinoma of the pancreas.
Authors: Michalaki Vasiliki , Vezakis Antonios , Frangoulidis George , Bramis Konstantinos , Theodosopoulos Thedosios , Tiniakos Dina , Konstandoulakis Manousos , Papadimitriou Christos
Published: July 2024

e16317

Background: Adenosquamous carcinoma of the pancreas (ASCP) is an aggressive, infrequent subtype of pancreatic cancer that combines a glandular and squamous component and is associated with poor survival. Data regarding adjuvant therapy remain controversial. Methods: Patients with advanced PASC from 2005 to 2021 were consecutively included in this retrospective study. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method. Results: Eighteen PASC patients treated surgically were included (median age, 69.3 years; males, 58.2%). All patients received adjuvant chemotherapy. Ten patients (55%) received newer platinum based regimen combination (FOLFIRINOX) and eight patients (45%) received gemcitabine-based regimens. Platinum based regimen as compared to gemcitabine regimen showed an improvement of overall response rate (42.5% and 12.3 %, p=0.001), PFS (median,10.4 versus 3.1 months, p=0.03) and OS (median, 15.8 vs 6.9 months, p=0.21).Multivariate analysis revealed that, among all patients (n=18), the following factors were independently predictive of poor survival: margin-positive resection (HR =3,15; 95% CI, 1.5-5.9; P<0.001), lymph node involvement (HR =2.9; 95% CI, 1.7 -7.5; P=0.003), and lack of inclusion of a platinum agent in the adjuvant regimen (HR =2.6; 95% CI, 1.5 -4.9; P=0.035). Conclusions: Given the rarity of ASC, optimal management remains poorly defined, particularly in the postoperative period. Therapies based on platinum chemotherapeutics may be preferable to all other chemotherapy regimens.
Yolk sac tumor of the liver: Presentation, diagnosis, and treatment review.
Authors: Paracha Awais , Kwait Brittany , Lee Amanda , Papale Anthony , Attanasi Michael , Hussain Fahad , Durrani Umar , John Veena S.
Published: July 2024

e16371

Background: Yolk Sac Tumor of the Liver (YSTL) is an extremely rare extragonadal germ cell tumor with gonadal origin and histology which presents in the liver. While uncommon, this tumor is often misdiagnosed due to the similarities between YSTL, HCC, and Hepatoblastoma (HB). As this cancer can present with serious mortality, our review aimed to evaluate clinical findings, diagnostic workup, and treatments in patients with YSTL. Methods: We performed a literature search in PubMed from 1950 to October 2023 using filters English language and full text with keywords “Yolk sac tumor of the liver”, “Endodermal Sinus tumor of liver”, “Hepatic Yolk sac tumor”, and “Hepatic Endodermal sinus tumor”. We also conducted a combined search query with all these search terms and “primary”. Patients were included in the study if they had primary YSTL and no other malignancy. Results: Our results looked at 19 patients ranging from 15 months to 64 years with median age being 27 years, including 13 female (68%) and 6 male (32%) patients, percentages reflect the total number of patients. The key presenting symptom in adults was abdominal pain (55%), while the key presenting symptom in children was abdominal distention (63%). All patients in the study had a diagnostic workup that included imaging and pathology. Imaging included CT Abdomen (68%) and MRI (37%), in 58% of patients a solitary mass was seen on imaging, while in 42% of patients multiple hepatic masses were seen. Histology workup mainly noted Shiller Duval Bodies(SDBs)(76%). Molecular Markers included AFP(42%), Alpha-1 anti-trypsin(A1AT)(26%), SALL4(21%), Pancytokeratin(PK)(11%), and Placental-like alkaline phosphatase(PALP)(11%). Treatment included chemotherapy(58%), surgery(47%), transplant(11%), and trans-arterial chemoembolization(5%). Out of the 11 patients who were treated with chemotherapy, 91% received the bleomycin, etoposide, and cisplatin (BEP) regimen. The remaining 9 % of patients received a regimen of cisplatin, adriamycin, and pepleomycin. Conclusions: YSTL is a unique tumor presenting in patients of all ages, tending to present vaguely often with abdominal pain or distension. Diagnostic workup often includes abdominal imaging (MRI and CT Abdomen) and pathology with a focus on SDBs on histologic examination and stains like AFP, A1AT, SALL4, etc. Treatment often focuses on surgery and chemotherapy, notably BEP. Though both HCC and HB traditionally present as a multifocal liver mass on imaging along with positive staining for AFP and PK, our study helps differentiate this tumor from others by emphasizing the importance of SDBs in diagnosis and highlighting new molecular markers to help make the diagnosis easier.
Fibrolamellar carcinoma registry: Opportunities and challenges.
Authors: Al Mahmasani Layal , Capanu Marinela , Losert Kurt , Lowery Maeve Aine , Hennessy Martina , Ray Mathew , Chambers Suzanne , Yaqubie Amin , Zarski Andrew , El Dika Imane H. , Light Joseph S. , La Quaglia Michael P. , O'Reilly Eileen M. , Abou-Alfa Ghassan K.
Published: July 2024

e16384

Background: Fibrolamellar carcinoma (FLC) is a rare form of primary liver cancer which affects young adults and adolescents without underlying liver disease or cirrhosis. The tumors are typically well circumscribed masses characterized pathologically by well differentiated polygonal hepatic cells with eosinophilic and granular cytoplasm surrounded by fibrous bands. DNAJB1 and PRKACA fusion is perceived as a dominant recurrent genetic alteration in FLC. FLC affects patients worldwide and a continued lack of an international database remains a knowledge gap. Further, there remains a poor understanding of FLC etiology, and major unmet need for more effective therapy. Methods: A patient-centered multi time-points, dynamic registry was developed by Memorial Sloan Kettering (MSK) in collaboration with Google and Maven Wave. The effort was supported by the Fibrolamellar Cancer Foundation (FCF). The study was opened worldwide except for the European Union pending the acquisition of the requiredGeneral Data Protection Regulation (GDPR) of data control and processing. The latter were assigned to Trinity College Dublin (TCD); a partner in this study. Participants were required to have a Google account to access the study. Demographic, clinical and response data were collected at baseline and at selected time points (monthly for up to 18 months). The aim of the registry was to provide a longitudinal understanding of the biography and natural history of the disease and outcomes. Results: Between May 2021 and December 2023, the study was broadcasted publicly worldwide through different venues including MSK, FCF, websites and Google engine. Only 14 patients responded. Table 1 summarizes the study sequence and patients’ enrollment. On average, the participants completed 41% of the monthly surveys. Four responders out of 5 patients were female, with a median age of 32 years (range 21-53). Conclusions: The registry provided a unique opportunity to access a broad global community of patients with FLC. Poor participation was key main limiting factor. Barriers include: (1) the presence of competing registries or studies for FLC, (2) technical limitations such as the exclusivity to access the registry to Google account. Follow-up emails may have been received in spam or junk folders, (3) complexities posed by the GDPR in Europe, and (4) patient-related factors including preoccupation with treatments and symptom management of their illness add to the disinterest in or inability to fill the monthly surveys. Unifying efforts and collaborations among caring physicians and scientists, medical centers, foundations, and patient advocacy groups across the world can help overcome the current challenges and accelerate the buildup of resources for research and practice improvement for the rare FLC. [Table: see text]
Decade-long insights into transperineal prostate biopsy in a west China population: Temporal trend, targeted and repeat biopsies, and pathological characterization.
Authors: Zhao Jinge , Cai Diming , Chen Yuntian , Dai Jindong , Chen Ni , Shen Pengfei , Zeng Hao
Published: July 2024

e17004

Background: Despite advances in prostate cancer (PCa) detection, the need for improving diagnostics and in-depth assessment of the latest prostate biopsy (PBx) techniques through extensive, longitudinal studies remains critical. Methods: Data from 10,378 PBx involving 10,038 patients were retrospectively examined. We detailed the yearly changes in PBx numbers and patient diagnoses, the real-world efficacy of PI-RADS scoring, MRI-targeted biopsy (MRI-TBx), and repeat PBx. We also outlined the detection rates and the clinical profiles of non-adenocarcinoma (non-AC) PCa. Results: A consistent annual increase in PBx was witnessed, with the positive rate climbing to approximately 55%. There was a gradual decline in median age, PSA levels, and M1 stage proportion among PCa patients, suggesting an earlier diagnosis trend. However, compared to Western populations, our center's patients had a significantly higher incidence of M1 stage (34% vs. 6%, P<0.001) and, within the M0 category, presented with older age and elevated baseline PSA levels. Integrating MRI-TBx into the 12-core systematic biopsy (SBx) led to a numerical improvement in PCa detection and enhanced ISUP grading accuracy. Merging MRI-TBx with a 6-core SBx achieved a median clinically significant PCa (csPCa) detection rate of 39.76% in men with PSA<20ng/mL, similar to that of MRI-TBx with a 12-core SBx (40.36%). Furthermore, we identified 1,455 men with non-AC PCa, occurring less in localized cases (about 15%) but more in metastatic cases (over 50%), and exhibiting more aggressive characteristics compared to adenocarcinoma-only cases. Besides, among the 305 individuals undergoing repeat PBx, 62 csPCa cases were identified, all of which exhibited lower positive cores, ISUP grading, and M1 stage incidence than men diagnosed by initial PBx. Conclusions: Analyzing a decade's worth of PBx data from one of the largest Asian cohorts offered pivotal insights into the evolving epidemiology and clinical profiles of PBx, which are essential for shaping future diagnostic approaches for PCa.
Docetaxel plus cis-platinum chemotherapy for the posterior line treatment of metastatic castrate-resistant prostate cancer with elevated neuron specific enolase.
Authors: Zhai Tingshuai , Ma Jinliang , Jiang Huanrong , Tian Jun
Published: July 2024

e17042

Background: This Study is to figure out the efficacy of docetaxel plus cis-platinum (DC) chemotherapy as the posterior line treatment for metastatic castrate-resistant prostate cancer (mCRPC) with elevated neuron specific enolase (NSE). Methods: We performed a retrospective study of men suffered mCRPC with elevated NSE from December 2019 to August 2022. All men were treated with DC after resistance to previous therapy. Biochemical progression-free survival (BPFS) were depicted using Kaplan-Meier curves. Results: 10 mCRPC patients aged 65.8 ± 7.0 (Median: 66.5, Range: 52-77) received DC for 1 to 10 cycles (Median: 7). Of the 10 patients, 2, 1 and 7 patients underwent DC as the 2nd, 3rd and 4th line therapy, respectively. 3 patients received previous chemotherapy and 9 patients underwent new endocrine therapy. All patients suffered bone metastases, 6 patients suffered distal lymph node metastases and 3 patients suffered visceral metastases. 6.1 ± 2.8 cycles (Median: 7, Range: 1-10) of DC were finished. Median follow-up time was 6.5 (Range: 2-11) months. After DC, Prostate specific antigen (PSA) response rate (>50%) was 90% and NSE response rate (>50%) was 60%. Median BPFS was 10 (Range: 4-18) months. Pain score declined from 6.6 ± 3.1 to 3.9 ± 2.4 evidently (P < 0.05) and Karnofsky (KPS) score increased from 80 ± 14.9 to 91 ± 16.0 significantly (P < 0.05). Of the 6 patients assessed by radiological examinations, 5 patients experienced partial response and 1patient achieved stable disease. Conclusions: Our pilot study showed docetaxel plus cis-platinum chemotherapy was effective for the mCRPC patients with elevated NSE resistant to multi-line therapies, indicating the potential value of DC for mCRPC with neuroendocrine differentiation.
Real-world clinical outcomes in Chinese patients with EGFR-mutated NSCLC progressed from first-line EGFR-TKI: A prospective multicenter study.
Authors: Tian Panwen , Wu Lin , Zhou Chengzhi , Tan Jie , Wang Ke , Luo Feng , Liu Yongmei , Guo Yubiao , Li Yinyin , Liu Zhe , Gong Youling , Wang Yongsheng , Li Weimin
Published: July 2024

e20547

Background: EGFR-TKIs is standard of care for treatment-naïve EGFR mutated ( EGFRm) advanced NSCLC (aNSCLC). The clinical outcome after 1L EGFR-TKI in clinical practice is not well studied prospectively. Herein, we reported the real-world clinical outcomes in Chinese EGFRm aNSCLC progressed from 1L EGFR-TKI. Methods: This prospective, observational study enrolled 300 Chinese patients (pts) from 16 sites between March, 2020 and August, 2021. At data cut-off date of August 27, 2023. 291 eligible pts were included into the full analysis set (FAS) and 225 pts in FAS received second-line EGFR-TKI or chemotherapy were included into outcome analysis set (OAS). The clinical outcome (PFS and OS, measured from 2nd line treatment) were presented. Results: The median age of 291 pts in FAS was 62 years, 57.0% was females and 29.3% pts with brain metastasis. EGFR mutation included 19del (143 pts, 49.1%), L858R (126 pts, 43.3%) and others (22 pts, 7.6%). 273 (93.8%) and 18 (6.2%) pts progressed from 1L 1G/2G EGFR-TKIs and 3G EGFR-TKIs, respectively. In OAS, overall mPFS and mOS in T790M + patients (90 pts) who received 2L 3G EGFR-TKIs were 14.7 (10.40-18.0) and 32 (25.20-NE) months, respectively. The mPFS and mOS by type of sample and T790M test results were presented in table. 85 pts with T790M- who progressed from 1L 1/2G EGFR-TKIs, including 51, 9 and 25 pts received 3G EGFR-TKIs, prior EGFR-TKIs plus local therapy, and chemotherapy as 2L therapy, respectively. The corresponding mPFS were 7.60 (95% CI, 4.70-10.40), 10.20 (2.30-14.90), and 4.90 (2.50-6.90) months, respectively. The corresponding mOS were 21.20 (12.10-NE), 16.60 (6.00-28.60), and 15.00 (9.40-NE) months, respectively. For T790M- patients with 19del (21 pts) and L858R (26 pts) mutation who received 2L 3G EGFR-TKIs, the mPFS was 21.00 (2.60-NE), and 8.00 (5.00-10.40) months, respectively. mOS was NE (21.00-NE) and 16.60 (8.20-24.60) months, respectively. 12 pts progressed from 1L 3G EGFR-TKIs, 10 and 2 pts received chemotherapy-based regimen and prior EGFR-TKIs plus local therapy as 2L therapy, respectively. The corresponding overall mPFS were 8.40 (95% CI: 1.20-11.80) months. The overall mOS was 14.20 (2.80-NE) months. Conclusions: The real-world treatment pattern and corresponding prognosis of EGFR-mutated NSCLC progressed from first-line EGFR-TKI were diverse, and among them those who received 3G EGFR-TKI at progression showed a better clinical outcome. These results supplemented the clinical evidence for the use of 3G EGFR-TKIs in EGFRm aNSCLC pts who progressed from 1L 1/2G EGFR-TKIs in the real-world setting. Clinical trial information: NCT04207775 . [Table: see text]
Efficacy and safety of PD-1 inhibitors plus metronomic oral vinorelbine in elderly pre-treated patients with metastatic non-small-cell lung cancer.
Authors: Li Lin , Yuan Yue , Gao Jiayi , Zhang Ping , Wu Xiaonan , Tang Min , Nie Xin , Ma Di , Zhao Zhe , Tian Yumeng
Published: July 2024

e20556

Background: The subsequent therapy of elderly non-small cell lung cancer (NSCLC) without driver oncogene has always been a challenge due to the poor performance status and multiple comorbidities, especially in those who acquired resistance to programmed cell death protein 1/programmed death-ligand 1 [PD-(L)1] blockade. Metronomic chemotherapy (MCT) is the frequent administration of chemotherapy drugs at lower doses each time which shows a better safety profile, antitumor angiogenesis, and immune modulatory effects compared with traditional chemotherapy. Here we designed an observational study to evaluate the efficacy and safety of PD-1 inhibitors plus metronomic oral vinorelbine(mOV) in elderly pre-treated metastatic NSCLC. Methods: Patients aged 65 years and above who had been histologically or cytologically confirmed unresectable stage III and IV NSCLC were recruited for this study. All the pts had no EGFR mutation, ALK fusions, or ROS1 fusions and received at least one systematic treatment. Pts received PD-1 inhibitors combined with mOV (30mg, TIW1, day 1-3-5 per week) for 6 cycles, followed by PD-1 inhibitors maintenance until disease progression or intolerable toxicities. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results: From May 2020 to June 2023, 23 pts were enrolled in the study. The median age was 70 with 18(78%) males. Median follow-up time was 22.8 months (range 3.9months-41.9months). The median PFS was 5.13 months (95%Cl: 3.1 months-7.1 months) and the median OS was 28.1 months (95%Cl: (15.2 months-NA). The ORR and DCR were 13% (95%C1: 1.44%-27.6%) and 69.6% (95%Cl: 49.2%-89.9%), respectively. The PFS (p = 0.459, HR = 0.671 95%CI 0.233-1.932) and OS (p = 0.483, HR = 1.607 95%CI 0.426-6.056) were similar between those pts who previously received immunotherapy (N = 16, 69.5%) and not. PD-L1 TPS didn’t affect the patient’s PFS (<1% vs≥1%, p = 0.078, HR = 2.648 95%CI 0.895-7.835 ) and OS(<1% vs≥1%, p = 0.306, HR = 2.202 95%CI 0.485-9.989). Adverse events (AEs) of any grade were observed in 20(86.9%) pts of which grade III-IV AEs occurred in 4 (17.4%) pts. These grade III-IV events consisted of interstitial pneumonia, pulmonary infection, leukopenia, and neutropenia. Immune-related adverse events (irAEs) occurred in 4 (17.4%) pts, of which grade III irAEs occurred in 2 (8.7%) patients with interstitial pneumonia. No grade 4 irAEs and grade 5 adverse events even occurred. Conclusions: The regimen of PD-1 inhibitors plus mOV for the subsequent therapy showed good overall survival benefits and safety in elderly patients with metastatic NSCLC without driver oncogene which suggests it is worth further exploration.
Cost-effectiveness of sotorasib as a second-line treatment for non-small cell lung cancer with KRASG12C mutation in China and the US.
Authors: 朱 亚宁 , Zhāng Peng , Xu Nong
Published: July 2024

e20567

Background: Sotorasib was used for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer with KRASG12Cmutation who had received at least one systematic therapy, showing good antitumor activity and safety. However, it was unclear whether the high-cost sotorasib was cost-effective. Methods: A Markov model was developed to compare the lifetime cost and efficacy of sotorasib to treat non-small cell lung cancer with KRASG12C mutation from the CodeBreak 200 randomized placebo-controlled trial, which included 345 patients with previously treated non-small cell lung cancer with KRASG12C mutation. Incremental cost-effectiveness ratio(ICER), quality-adjusted life-year (QALY), incremental QALY were calculated for the 2 treatment strategies. One-way sensitivity analysis was used to investigate the factors that had a greater impact on the model results, and tornado diagram was used to verify the model stability, probabilistic sensitivity analysis was performed by Monte Carlo simulation, random factors were introduced into the model to simulate a certain number of large samples, and the results were presented as cost-effectiveness acceptable curves. Results: This economic evaluation of data from the CodeBreak 200 randomized trial. In China, sotorasib generated 0.44 QAYL with a total cost of $84372.59. Compwered with docetaxel, the ICER value of sotorasib was $102701.84/QALY, which was higher than WTP, so sotorasib had no economic advantage. In the US, sotorasib obtained 0.35 QALY more than docetaxel, ICER was $15,976.50 /QALY, which was low than WTP, indicating that the increased cost of sotorasib was acceptable. Conclusions: Sotorasib had cost effect from the perspective of the US. Howere, sotorasib had no cost effect from the perspective of China, and only when the willingness to pay(WTP) exceeds $102,500, the probability of sotorasib having cost effect increases from 0 to 49%.
Characteristics, treatment patterns, and prognostic factors in small cell lung cancer transformation of advanced non-small cell lung cancer with epidermal growth factor receptor mutation after tyrosine kinase inhibitor therapy.
Authors: Liao Ying-Ting , Chiang Chi-Lu , Sun Ruei-Lin , Yeh Yi-chen , Huang Hsu-Ching , Shen Chia-I , Tseng Yen-Han , Luo Yung-Hung , Chen Yuh-Min , Whang-Peng Jacqueline
Published: July 2024

e20569

Background: Small cell lung cancer transformation in advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation following tyrosine kinase inhibitor (TKI) therapy poses a challenging clinical scenario. This study aims to explore the characteristics, treatment patterns, and prognostic factors associated with this transformation. Methods: A total of 41 patients with transformed SCLC (tSCLC) were included. Patient characteristics, treatment details, and laboratory data were collected. Re-biopsy specimens and subsequent treatments were analyzed. Statistical analyses were conducted to identify factors associated with treatment response and survival outcomes. Results: The median age of the patients was 61.7 years old, with a median time from TKI treatment to small cell transformation of 22.2 months. The majority were female (58.5%), never smokers (80.5%), with 53.7% having stage IVB disease prior to EGFR-TKI treatment. The most prevalent initial EGFR mutation was exon 19 deletion (56.1%), and afatinib (46.3%) was the most commonly used EGFR-TKI. EGFR mutation analysis was performed in 68.3% of the tSCLC specimen, and acquired T790M was detected in 7.1% of the patients. Treatment patterns after transformation included various systemic therapies, with the most (63.4%) receiving etoposide plus platinum (EP) based chemotherapy in the first line setting. Among all the patients, 56.1% received EGFR-TKI and 22% received immune checkpoint inhibitors (ICI) throughout the post-transformation treatment course. Anemia (Hgb < 10g/dL) and ever use of EP were significant factors associated with post-transformation survival. The median progression-free survival (PFS) of the first line treatment was 3.27 months, and the overall survival (OS) was 10.43 months post transformation. Conclusions: Small cell lung cancer transformation in advanced NSCLC with EGFR mutation after TKI therapy is associated with diverse clinical characteristics and dismal outcomes. We presented the complexity of managing these cases in real-world practice. Anemia and ever use of EP affected post-transformation survival. Further research is warranted to optimize therapeutic strategies for this unique subset of patients.