tbuckley/cabot-search huggingface dataset:
Recurrence patterns and surveillance strategies in long-term survivors of resected pancreatic cancer.
Authors: Michael S. May, Liam James Stanton, Jacob K. Jamison, Benjamin May, Alissa M. Michel, Alexander G. Raufi, Winston Wong, Fay Kastrinos, Melissa Kate Accordino, Dawn L. Hershman, Gulam Abbas Manji, Linda Wu
Journal: Journal of Clinical Oncology (2024)

e16361 Background: Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer-related mortality in the United States. After resection, the 2-year disease-free survival is &lt; 50%. Surveillance guidelines after resection vary significantly between expert groups. The level of evidence is particularly weak for patients who are alive and disease-free after 2 years. Our objective was to report rates and predictors of recurrence in this population. Methods: We reviewed all patients who underwent resection of stage I-III PDA at Columbia University Irving Medical Center from 2011-2022. Eligibility criteria included patients who were alive and disease-free at 2 years after diagnosis. Demographic, surgical, and treatment characteristics were recorded. Imaging studies and tumor markers were reviewed and median time between studies after 2 years of follow up was determined. Recurrence was confirmed histologically or radiologically. Follow up and survival times were calculated using Kaplan Meier statistics. Associations between patient characteristics and recurrence risk were evaluated using a Cox proportional-hazards regression adjusted for demographic and treatment characteristics. Results: We reviewed 743 patients and 225 met eligibility criteria. The median age at diagnosis was 67.5 years. Median interval between surveillance imaging was 59 days and median interval between CA 19-9 draws was 41 days. After a median follow-up of 5.2 years from diagnosis, 84/225 (37%) patients experienced a late recurrence. Of these, 35% (29/84) had local recurrence, and 65% (55/84) had distant recurrence. The most common distant sites were lung (51%) and liver (27%). Lymph node positivity at resection was associated with late recurrence risk (p = 6x10 -6 ), but T-stage (p = 0.5), margins (p = 0.9), age (p = 0.2) and chemotherapy receipt (p = 0.3) were not. Of the 72 patients with CA 19-9-producing tumors (baseline CA 19-9 &gt; 37 U/mL) and complete normalization of CA 19-9 postoperatively, 30 patients had recurrence with CA 19-9 checked in the 9 months preceding recurrence. CA 19-9 re-elevation preceded recurrence in 83% (25/30) of late recurrences. Median time from CA 19-9 elevation to confirmation of recurrence was 5 months. Conclusions: The rate of recurrence for patients with PDA who are disease-free 2 years after diagnosis is lower than that for patients in their first 2 years. The most common sites of late recurrence are local and lung. For long-term PDA survivors with CA 19-9 producing tumors, serial CA 19-9 monitoring may be used to guide imaging. Positive lymph nodes at resection identify patients who are at highest risk for late recurrence.
An NCDB analysis of the predictive factors associated with the receival of tumor resection in mucinous cystadenoma of the pancreas.
Authors: Shalika Devireddy, Peter T. Silberstein, Jasleen Kaur Chaddha
Journal: Journal of Clinical Oncology (2024)

e16356 Background: Mucinous cystadenoma (MCN) of the pancreas is characterized by mucin-producing cystic tumors that may lead to pancreatic ductal obstruction. While many of these cystic lesions are benign, there exists a notable risk for malignancy. Presently, the standard approach to managing MCN involves surveillance. Surgical resection is considered after evaluating histological features, the patient's age, surgical risk, and tumor size. Previous studies have linked surgical resection to favorable overall outcomes. However, no studies have investigated the predictive factors correlated to receiving surgery in MCN patients. This study aims to utilize the National Cancer Database (NCDB) to analyze factors that determine receival of tumor resection in patients with MCN of the pancreas. Methods: The NCDB was used to identify patients diagnosed with MCN of the pancreas from 2004 to 2019 using the histology codes 8470 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Multilevel Logistic Regression were performed, and data were analyzed using SPSS version 27. Statistical significance was set at α = 0.05. Results: 827 patients with MCN of the pancreas formed the initial sample. 552 patients received a tumor resection whereas 274 patients did not receive surgery ( 66.7% vs 33.1%, respectively). Surgical patients experienced significantly longer overall survival than nonsurgical patients ( 111.2 months vs. 20.1 months, p &lt; 0.001). Complete tumor resection with no residual tumor cells was associated with improved outcomes in MCN( p &lt; 0.001). Metastasis to distant sites was associated with decreased likelihood of receiving surgery ( p &lt; 0.001). Well and moderately differentiated disease, stage I, II, and II disease, treatment at an academic facility, and private insurance status were associated with increased likelihood of receiving tumor resection ( p &lt; 0.001). Income status and race did not appear to impact overall survival of these patients. Adjuvant therapies did not appear to impact overall survival of these patients. Conclusions: The results of this research align with other studies, affirming that surgical resection yields superior outcomes in patients with MCN of the pancreas. Factors such as well or moderately differentiated disease, early-stage diagnosis, treatment at academic facilities, and private insurance status increased the likelihood of tumor resection. Distant metastasis reduced the likelihood of receiving surgery. Complete tumor removal without presence of residual tumor cells post-surgery is correlated with improved survival. Income status and race did not appear to impact overall survival, and adjuvant therapies showed no discernible effect. To improve current treatment protocols for patients with MCN of the pancreas, more research needs to be conducted on the predictive factors of receiving surgery.
Primary and secondary resistance to immune checkpoint inhibitors in hepatocellular carcinoma.
Authors: Xiaowen Cui, Minghao Ruan, Yao Li, Cheng Yang, Liuyu Zhou, Jin Zhang, Riming Jin, Dong Wu, Ruoyu Wang
Journal: Journal of Clinical Oncology (2024)

e16209 Background: Immunotherapy have revolutionized the therapeutic landscape of hepatocellular carcinoma (HCC). However, clinical features affecting immune resistance remain largely unknown. This retrospective cohort study aims to investigate the outcomes and characteristics of pts with resistance to immunotherapy in HCC. Methods: Pts with HCC who received immune checkpoint inhibitors (ICIs) of PD-1/PD-L1 antibodies at Eastern Hepatobiliary Surgery Hospital between 2016 and 2021 were retrospectively enrolled and screened for eligibility. Recommended by the Society for Immunotherapy of Cancer (SITC), primary resistance was defined as when pts were exposed to ICIs therapy for at least 6 weeks and with the best overall response (BOR) of PD or SD for less than 6 months. Secondary resistance was defined as pts having disease progression after the initial objective response (CR/PR) or SD for more than 6 months. The durable response group consists of pts with the durable response (CR, PR, or SD) for more than 6 months without progression at data cutoff. Time to progression (TTP), overall survival (OS) and clinicopathological features of HCC pts were compared between groups. Subsequent management after resistance and post-progression survival (PPS) were also analyzed. Results: Of 496 pts included, 229 (46.2%) and 141 (28.4%) pts developed primary resistance and secondary resistance, and 126 (25.4%) pts achieved a durable response. The median follow-up was 22.8 months. For pts with primary resistance, secondary resistance, and durable response, the median TTP was 2.83 [2.56-3.09] months, 11.93 [10.45-13.40] months, and not reached, respectively. Whereas the median OS was 12.83 [10.36-15.30] months, 31.53 [28.09-34.97] months and not reached, respectively. Multivariate logistic regression revealed that the Child-Pugh score (Child-Pugh B versus A, OR 3.28 [1.51-7.13], p= 0.003), BCLC stage (BCLC B versus A, OR 3.55 [1.70-7.43], p= 0.001; BCLC C versus A, OR 2.88 [1.47-5.65], p= 0.002), and combinational therapies (ICIs+bevacizumab versus monotherapy, OR 0.14 [0.04-0.51], p= 0.003; ICIs plus lenvatinib+monotherapy, OR 0.43 [0.26-0.72], p= 0.001) were independently associated with primary resistance, and only the combination of ICIs plus bevacizumab (ICIs+bevacizumab versus monotherapy, OR 0.10 [0.01-0.52], p= 0.007) was independently associated with secondary resistance. AFP levels and post-progression therapies were independently associated with PPS in pts with primary resistance, while post-progression therapies were independently associated with PPS in pts with secondary resistance. Conclusions: Risk for resistance was significantly lower among pts who received ICIs plus bevacizumab.High AFP levels independently predict the survival of pts after primary resistance to immunotherapy. ICI-based maintenance therapy after resistance may provide a significant survival advantage for HCC pts.
Effect of malnutrition on cirrhotic patients with hepatocellular carcinoma: A nationwide study.
Authors: Adham Obeidat, Nour Mansour, Ratib Mahfouz, Mohammad Aldiabat
Journal: Journal of Clinical Oncology (2024)

e16250 Background: Liver cancer is the sixth most common cancer and the third leading cause of cancer mortality worldwide. There are two main types of primary liver cancers; hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma. HCC accounts for around 80% of primary liver cancer cases. Generally, HCC develops in genetically susceptible individuals with risk factors, especially in the presence of cirrhosis. Cirrhosis is a systemic disease, and malnutrition is a key feature as well as an important complication which can be associated with worse outcomes. In this study, we aim to characterize the potential effects of malnutrition on HCC patients with underlying cirrhosis. Methods: The United States Nationwide Inpatient Sample (NIS) was used to extract hospitalization data of patients admitted between 2016 to 2018. Using ICD10 revision codes, we identified adults with the diagnosis of cirrhosis who have HCC with concomitant malnutrition, including sarcopenia. The control group included cirrhotic HCC patients without malnutrition. The primary outcome was the in-hospital mortality. Secondary outcomes included encephalopathy, ascites, variceal bleed, hepatorenal syndrome (HRS) and length of stay (LOS). Multivariate logistic regression was used to adjust for relevant variables. Results: We identified 423,158 patients admitted with cirrhosis. 20,582 had HCC, and of those, 2560 patients had the diagnosis of malnutrition. In this group of patients, the mean age was 59.85 years. 30% were females and 62% were Caucasians. When adjusted to other relevant variables, malnutrition was associated with increased in-hospital mortality (OR 1.40; P-value 0.000). It was also associated with an increased chance of developing encephalopathy (OR 1.42; P-value 0.000), ascites (OR 1.62; P-value 0.000), and HRS (OR 1.33; P-value 0.000). Moreover, it was associated with increased LOS (OR 1.99; P-value 0.001). Other factors associated with increased in-hospital mortality in cirrhotic HCC patients are described in the table. Conclusions: Malnutrition is a common complication in patients with cirrhosis. If identified, it can be treated efficiently. In this study, cirrhotic HCC patients with malnutrition had an increased chance of mortality. Further, they were at increased risk for cirrhosis decompensation and other in-hospital complications, which in turn can lead to increased LOS and therefore increased financial burden. We recommend that clinicians pay attention to patients with malnutrition and to treat them in order to prevent these complications. [Table: see text]
Clinical–epidemiological characterization of cervical cancer in a middle-income country.
Authors: Walter Morquecho, Mario Argüello, José Luís Reyes, Fausto Emiliano Pulla, Víctor Hugo Ávila, Lorena Paola Estrada, Guillermo Paulson, Mayra Santacruz
Journal: Journal of Clinical Oncology (2024)

e17514 Background: Despite significant advances in prevention and treatment, cervical cancer remains a global public health threat, claiming the lives of hundreds of thousands of women each year. It disproportionately affects women in low- and middle-income countries, where access to vaccination, screening, and early diagnosis is often limited. The present study aims to determine this pathology's clinical and epidemiological characteristics. Methods: This is an observational, descriptive, retrospective, and cross-sectional study. Information from the digital medical records of patients with cervical cancer from SOLCA Guayaquil from January 2010 to December 2014 was used. Results: 1909 medical records of patients with cervical cancer were reviewed during the study period; 211 were excluded for not meeting eligibility criteria, leaving 1698 to be evaluated. Regarding stages (I-II-III-IV), the most frequent was stage II (A-B), 54.2% of them, squamous cell carcinoma (44.6%), and adenocarcinoma (9.6%). 32.2% correspond to resectable cancers (IA-IIA), and 67.8% to non-resectable cancers. The mean age was 55 years, the median was 54, and the mode was 45. The absence of these comorbidities was the most frequent (47.8%), then kidney (6%) and ureteral (4.7%). Conclusions: The age of presentation of cervical cancer in this health center is higher than the global average but closer to what is seen in Latin America. The clinical stages are relatively advanced at diagnosis. The most frequent histopathological types were squamous cell carcinoma and adenocarcinoma. What predominated was the absence of comorbidities. [Table: see text]
Deciphering the correlation between Chr3q26.2 amplification through homologous recombination deficiency and improved survival in ovarian cancer under platinum-based adjuvant therapy.
Authors: Ning Ding, Yaqin Wu, Xiaotian Zhao, Minyi Zhu, Qiuxiang Ou, Jiaohui Pang, Luxi Ruan, Ying Zhang, Wei Sun, Xiaoxiang Chen
Journal: Journal of Clinical Oncology (2024)

e17537 Background: Discriminant copy number alterations (CNAs) have been linked to aberrant DNA repair mechanisms. This study aimed to identify CNA-based biomarkers, alongside homologous recombination deficiency (HRD) scores for ovarian cancer patients receiving platinum (Pt)-based chemotherapy, especially in BRCA1/2 wild-type or HRD-low patients. Methods: Fourteen most prevalent and significant focal CNA regions (seven amplification and seven deletion) were examined to investigate their correlations with HRD scores via SHAP values of an XGBoost model and the effectiveness of Pt-based adjuvant chemotherapy in a cohort of high-grade serous ovarian cancer (HGSC) patients (TCGA cohort, N=576), and the results were validated in a separate Chinese ovarian cancer cohort (test cohort, N=457). An in-house developed next-generation sequencing HRD pipeline (GeneseeqPrime HRD) was used to determine HRD scores. Histological subtypes, molecular features, and potential molecular mechanisms associated with the identified biomarkers were further explored. Results: Of 14 high-level CNA regions identified by GISTIC in the TCGA cohort, Chromosome 3q26.2 amplification [ Chr3(q26.2) Amp, a prevalence of 30.7%] was associated with increased HRD scores in both BRCA1/2-altered ( p=0.01) and wild-type HGSCs ( p=0.03). Consistently, in the test cohort, higher HRD scores ( p&lt;0.01) and elevated chromosome instability scores ( p&lt;0.01) were observed in Chr3(q26.2) amplified samples. Among 406 patients administrated with Pt-based adjuvant chemotherapy in the TCGA cohort, those with Chr3(q26.2) Amp exhibited a relatively high sensitivity rate ( p=0.09) and significantly superior disease-free survival after adjusting for HRD score, patient age, tumor stage, and residual disease [hazard ratio (HR): 0.65, 95% confidence interval (CI): 0.48–0.88] when compared to those without, representing Chr3(q26.2) Amp as an independent predictive biomarker. Similar results were obtained in 78 patients using Pt-based adjuvant chemotherapy in the test cohort (HR: 0.68, 95% CI: 0.40–1.15). Moreover, Chr3(q26.2) Amp was more prevalent in HGSCs harboring BRCA1/2 or TP53 aberrations than other histological subtypes driven by PIK3CA, PTEN or KRAS mutations ( p&lt;0.01). In comparison to HGSCs without Chr3(q26.2) Amp, Chr3(q26.2) amplified HGSCs exhibited higher Ragnum hypoxia scores ( p&lt;0.01) and a total of four overexpressed proteins, including p62 ( p&lt;0.01), PIK3CA ( p&lt;0.01), CCNB1 ( p&lt;0.01) and TSC1 ( p&lt;0.01), indicative of suppressed homologous recombination repair pathway and cycle cell arrest. Conclusions: Chr3(q26.2) Amp emerges as a promising biomarker for Pt-based adjuvant chemotherapy in ovarian cancer, potentially reflecting a hypoxia-induced etiology through suppressed homologous recombination repair pathway.
Molecular characteristics of non-human papillomavirus driven cervical adenocarcinoma and adenosquamous carcinoma.
Authors: Chyong-Huey Lai, Chiao-Yun Lin, Ren-Chin Wu, Angel Chao
Journal: Journal of Clinical Oncology (2024)

e17532 Background: Cervical cancer is the fourth most common malignancy in women worldwide. Although infection from human papillomavirus (HPV) has been the major cause of cervical cancer, about 3-8% of cervical cancer cases are HPV-negative. Clinical data showed that patients with HPV-negative cervical cancer had significantly lower DFS than those with HPV-positive cervical cancer. The detection of HPV DNA tends to be lower in adenosquamous carcinoma (AC/ASC) than in squamous cell carcinoma. Because the mechanism of HPV-negative cervical cancer development is unclear, this study aims to find the pattern of differential gene expression in HPV-negative AC/ASC and verify the underlying potential mechanism. Methods: In this study, we aimed to exam the differential gene expression profiling by exome-capture RNA sequencing on formalin-fixed, paraffin-embedded tumor tissue of prospectively enrolled cervical AC/ASC patients (HPV-negative: HPV-positive: 1:1) and validate the selected biomarkers on the remaining (unmatched; n = 110) prospective cohort and the 274 retrospective cohort patients. Subsequently, dysregulated differentially expressed genes specifically existed in HPV-negative cervical AC/ASC tissues and HPV-negative cell lines were validated by Western blotting, enzyme-linked immunosorbent assay (ELISA), and immunohistochemical staining (IHC staining). Results: Exome-capture RNA sequencing on HPV-negative and age/grade matched HPV-positive AC/ASC (10:6) for discovery initially. We found differentially activated WNT pathway from HPV positive/negative AC/ASC in the prospective cohort. In the preliminary results of 28 prospective cohort patients, SOX17 and MMP7 highly expressed genes in HPV-negative (n = 13) then the HPV-positive (n = 11) cervical AC/ASC by IHC staining (p = 0.1029 and p = 0.0306, respectively). Moreover, plasma MMP7 levels were upregulated in HPV-negative AC/ASC (n = 10) compared with HPV-positive AC/ASC (n = 17) (p = 0.0086) by ELISA analysis in the prospective cohort. Conclusions: Further studies and more analyses will be continued to investigate the effects of changes in the expression of SOX17 and MMP7 related mechanisms, and targeting WNT/SOX17/MMP7 pathways specifically associated with HPV-negative AC/ASC to provide new insights into the early screening and effective treatment of HPV-negative AC/ASC.
Overall survival and patterns of care for women with rare ovarian cancers: A prospective study from the Australian National Gynae-Oncology Registry (NGOR).
Authors: Mahendra Naidoo, Clare L. Scott, Orla McNally, Rob Rome, Sharnel Perera, Yeh Chen Lee, Aleesha Whitely, Michael Burling, Lyndal Anderson, Paul Cohen, Gary Edward Richardson, Michael Friedlander, Alison Brand, Simon Hyde, Michael Bunting, Tom Jobling, John Raymond Zalcberg
Journal: Journal of Clinical Oncology (2024)

e17554 Background: Ovarian cancer (OC) is a heterogenous group of malignancies, most of which are rare. Data on patterns of care and survival of the most-rare sub-groups of OC (incidence rates &lt; 6 per 100,000) in the real-world setting is limited. This study aims to describe patterns of care and overall survival (OS) for women with rare ovarian cancers in Australia. Methods: Clinical data were sourced from the NGOR and assessed for accuracy and completeness. High grade serous and endometrioid OC subtypes were excluded. Due to incompleteness of survival follow-up data, 3-year OS was only calculated for the state of Victoria. Results: Data on 2812 women with newly diagnosed OC from 2017-2023 within NGOR were collected and 716 women were subsequently identified with rare subtypes of OC. The 5 sub-types with the highest incidences were clear cell (n = 168, 23.4%), mucinous (n=151, 21.1%), adult granulosa cell (n=111, 15.5%), low grade serous (n=98, 13.7%) and carcinosarcoma (n=59, 8.2%). A further 23 additional rare subtypes included germ cell tumours and sex cord stromal tumours. The median follow-up time was 2.6 years and median age at diagnosis was 55 years. Most women had an ECOG 0-1 performance status (n=551, 77.0%). The primary treatment modality was surgery only (n=360, 50%), followed by surgery and systemic therapy (n = 317, 44.2%), systemic therapy only (n=28, 3.9%) and no treatment (n=11, 1.5%). Most women were discussed at a multi-disciplinary meeting (n=701, 97.9%). The diagnosis was confirmed on histology for all women. The 30-day post-operative adverse events (Clavien-Dindo &gt;III severity) was 3.6 % (n=26), with the highest rate of post-operative events in the carcinosarcoma group of 12% (n=6). Using Fisher’s exact test across the 5 most common sub-types described above, there were significant differences in treatment modalities (p&lt;0.001), rates of 30-day post-operative events (p=0.002), age adjusted charlson comorbidity index (p&lt;0.001) and metropolitan versus remote regional status (p=0.007) between the sub-types. Survival at 3 years for these five sub-types of rare OC within the state of Victoria are summarised in the table. The highest 3-year OS was in adult granulosa and low grade serous sub-types. Conclusions: This is a large, real-world analysis of patterns of care and survival for women with rare sub-types of OC. Combining data with international sites will likely further enhance research on patterns of care and outcomes for women with rare OC. [Table: see text]