Median Disease-free Survival Time Research Articles

Clinical analysis of 12 cases of ovarian yolk sac tumor

Objective: To investigate the diagnosis, treatment and prognosis of ovarian yolk sac tumor (OYST). Methods: The clinicopathological data and follow-up data of 12 patients with OYST admitted to the Affiliated Hospital of Qingdao University from January 2013 to December 2020 were retrospectively analyzed, and the diagnosis, treatment and prognosis of OYST patients were summarized. Results: (1) The age of 12 patients with OYST ranged from 11 to 37 years, with a median age of 20 years. At the first visit, all 12 patients had pelvic masses. Reasons for seeing a doctor: 6 cases of abdominal distension and abdominal pain, 4 cases of mass in the lower abdomen, 1 case of vaginal bleeding, and 1 case of appendicitis. International Federation of Obstetrics and Gynecology (FIGO) 2014 staging: 4 cases in stage Ⅰa, 2 cases in stage Ⅰc, 1 case in stage Ⅱc, 4 cases in stage Ⅲc, and 1 case in stage Ⅳb. (2) All 12 patients were examined by color Doppler ultrasound before operation, among which 10 cases showed unilateral adnexal masses and 2 cases bilateral adnexal masses. The median maximum diameter of tumor was 16.5 cm (range: 6.0-28.0 cm). The preoperative levels of alpha fetoprotein (AFP) in 12 patients (all >1 210 μg/L) were significantly higher than normal (<25 μg/L). Among the 11 patients with cancer antigen 125 (CA125) detection results, 9 patients showed elevated serum CA125 levels. (3) Among the 12 patients, 8 young infertile patients who needed to preserve their reproductive function underwent appendectomy, 3 infertile patients underwent staged surgery for ovarian malignant germ cell tumor, and only one bilateral lesion and infertile patient underwent unsatisfactory staged surgery for ovarian malignant germ cell tumor. Of the 12 patients, 11 patients were given combined chemotherapy regimen of bleomycin, cisplatin, and etoposide (BEP) after operation. One patient without chemotherapy developed metastasis 3 months after operation, and was given BEP chemotherapy, and her condition was controlled. (4) The deadline for follow-up was December 31st, 2022, and the median follow-up time was 60 months (range: 25-115 months). All the 12 patients survived without tumor during the follow-up period, and the median disease-free survival time was 84.5 months (range: 25-115 months). Conclusions: OYST mostly occurs in children and young women. Color Doppler ultrasound examination and serum AFP and CA125 detection have diagnostic value for OYST. Surgical treatment after diagnosis of OYST includes surgery to preserve reproductive function and timely and standardized chemotherapy after operation. The prognosis of patients is good regardless of stage.

Efficacy and safety of adjuvant radiation therapy in localized adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is rare and have high rates of recurrence and mortality. The role of adjuvant radiation therapy (RT) in localized ACC was controversial. We conducted a retrospective study in our center between 2015 and 2021 to evaluate the efficacy and safety of adjuvant RT in localized ACC. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used to estimate the independent risk factors. Adverse events associated with RT were documented according to the toxicity criteria of the radiation therapy oncology group (RTOG) and the common terminology criteria for adverse events (CTCAE v5.0). Of 105 patients with localized ACC, 46 (43.8%) received adjuvant RT after surgery. The median radiation dose was 45.0Gy (range:30.0-50.4) and median follow up time was 36.5 (IQR: 19.7-51.8) months. In comparison to the no adjuvant RT group, patients with adjuvant RT had better 3-year OS (87.9% vs 79.5%, P=0.039), especially for patients with ENSAT I/II stage (P=0.004). Adjuvant RT also improved the median DFS time from 16.5months (95%CI, 12.0-20.9) to 34.6months (95%CI, 16.1-53.0). Toxicity of RT was generally mild and moderate with six grade 3 events. Postoperative adjuvant RT significantly improved OS and DFS compared with the use of surgery alone in resected ACC patients. Although this retrospective study on RT in localized ACC indicates that RT is effective in ACC, its findings need to be prospectively confirmed.

The impact of neo/adjuvant treatment choices on prognosis for surgically treated small-cell neuroendocrine carcinoma of the cervix.

Small-cell neuroendocrine carcinoma of the cervix (SCNCC) is a rare and aggressive tumor with a poor prognosis. Surgical resection followed by adjuvant therapy is the standard treatment for early-stage disease but the influence of different neo/adjuvant treatment approaches remains unclear. Retrospectively, we collected patients' characteristics and treatments in two medical centers. Disease status and survival outcomes were renewed through follow-up. Statistics analysis mainly included Kaplan-Meier methods for survival curve estimation, log-rank test for survival curve comparison, and Cox proportional hazards models for independent prognostic factors prediction. Finally, 51 patients treated by radical surgery between January 2010 and April 2020 were enrolled with a median age of 50 years (range: 32-68). 12 (23.5%) patients were at stage IIIC1 according to the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging systems and the rest were at the early stage. The mean tumor size was 3.6±1.3 cm. Pathological examination found 24 cases with pure SCNCC and 27 cases with admixed SCCC. 29 (56.9%) patients had deep stromal infiltration and 19 (37.3%) patients had lymphovascular space invasion. 34 (66.7%) patients received neo/adjuvant chemotherapy and pelvic radiation was conducted in 41 (80.39%) patients with a median dose of 46 Gy (range: 40-50.4 Gy). The median follow-up time was 25.0 months. The median disease-free survival (DFS) time was 23.0 months. 27 (52.9%) patients developed distant metastasis and 14 (27.5%) experienced local failure. The median overall survival (OS) was 32.0 months. Univariate and multivariate analysis showed neoadjuvant chemotherapy as negative (HR=2.081, 95% CI 1.030-4.203, p=0.041) and adjuvant chemotherapy (HR=0.409, 95% CI 0.213-0.784, p=0.020) as positive independent prognostic factor for DFS. For OS, only lymph node metastasis was confirmed as an independent prognostic factor in both univariate analysis (HR=1.528, 95% CI 1.011-2.308, p=0.044) and multivariate analysis (HR=1.697, 95% CI 1.041-2.768, p=0.034). In conclusion, for surgically treated SCNCC, adjuvant chemotherapy showed a positive influence on DFS while neoadjuvant chemotherapy harmed DFS. OS was unaffected by either treatment choice.

Evaluation of the safety and feasibility of electrochemotherapy with intravenous bleomycin as local treatment of bladder cancer in dogs

Local treatment of canine urothelial carcinoma (UC) of the bladder is a challenge. More than 90% of the cases invade the muscular layer, more than 50% develop on bladder sites with a difficult surgical approach and often requiring radical surgical procedures. This study aims to evaluate the safety and feasibility of electrochemotherapy (ECT) with intravenous bleomycin (BLM) as a local therapy for bladder UC. This prospective study included 21 dogs with spontaneous bladder UC. Regional/distant metastases and neoplastic infiltration of the serosa was considered the main exclusion criteria. We had no deaths during ECT or in the immediate postoperative period, and no suture dehiscence. Most dogs (19/21) developed mild adverse effects, whereas two dogs developed ureteral stenosis. Complete response (CR) was achieved in 62% of the cases (13/21), while partial response (PR) was achieved in 24% (5/21). The median survival and disease-free survival times were 284 and 270 days, respectively. Overall survival was significantly better in the dogs who achieved a CR. In conclusion, ECT was well-tolerated in dogs with UC, demonstrating its safety and feasibility. These data pave the way for new studies aimed at evaluating the effectiveness of ECT in canine bladder UC as a translational model for human disease.

Optimal Treatment Strategies for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Real-World Triple Cohort Analysis Using Propensity Score Matching.

This study aims to identify the most effective treatment approach and compares the survival rates, along with complications, in patients with locally resectable esophageal squamous cell carcinoma (ESCC) who were treated with one of the three treatment patterns: neoadjuvant chemotherapy followed by surgery (NCT+S), neoadjuvant chemoradiotherapy followed by surgery (NCRT+S), or surgery followed by chemoradiotherapy (S+CRT). We conducted a retrospective analysis of the medical records of ESCC patients who received one of these treatments between March 2015 and March 2022. This analysis aimed to identify differences in long-term survival, pathological responses, and complications across the three treatment groups. To address potential confounding factors, propensity score matching (PSM) and Cox proportional hazards models were utilized. This study included a cohort of 715 patients: 197 in the NCT+S group, 188 in the NCRT+S group, and 330 in the S+CRT group, all meeting the selection criteria. After PSM, the median disease-free survival (DFS) time was 38.9 months, 25.6 months, and 15.3 months for NCRT+S, NCT+S, and S+CRT groups, respectively. There were statistically significant differences in the 5-year DFS and 5-year OS among the three groups (P=0.04 and P=0.02, post-matching, respectively). Notably, neoadjuvant therapy showed a correlation with increased postoperative anastomotic leakage rates (17.5% in NCRT+S, 10% in NCT+S, and 5% in S+CRT; P=0.03, post-matching), regardless of the PSM adjustment. The findings indicate that neoadjuvant therapy before surgery offers a significant survival advantage over postoperative adjuvant therapy for patients with locally advanced resectable ESCC. Despite similar safety profiles, neoadjuvant therapy appears to be associated with a higher incidence of anastomotic leakage after surgery.

Efficacy analysis of surgical combined with postoperative adjuvant therapy for T3 gallbladder carcinoma: a multicenter retrospective study

Objective: To explore the clinical value of adjuvant therapy in patients with T3 gallbladder cancer (GBC) who have undergone R0 resection. Methods: Clinical and pathological data from 415 patients with T3 GBC who underwent surgical treatment in 7 tertiary centers in China from January 2013 to December 2018 were collected,including 251 males and 164 females,aged (61±11)years (range: 26 to 88 years). Depending on whether to receive adjuvant therapy after radical resection,the patients were divided into the radical resection group alone (group A,n=358) and the radical resection combined with the postoperative adjuvant therapy group (group B,n=57). The general data of the two groups were matched 1∶1 by propensity score matching method,and the caliper value was 0.02.Clinicopathological characteristics,overall survival and disease-free survival of the two groups were compared.The Cox regression model was used for multivariate analysis,and patients with at least one or more independent risk factors were classified as high-risk clinicopathological subtypes. Subgroup analysis was performed to assess the clinical value of adjuvant therapy after radical resection in patients with high-risk clinicopathological subtypes. Results: After the matching,there were 42 patients in each of the two groups. The incidence of gallbladder cancer and the number of dissected lymph nodes in group B after cholecystectomy were higher than those in group A (χ2=9.224,2.570,both P<0.05). There were no significant differences in overall survival rate and disease-free survival rate between the two groups before and after matching (all P>0.05). The results of the univariate and multivariate analysis showed that CA19-9>39 U/ml,nerve invasion,tumor location (liver side or bilateral),TNM stage ⅢB to ⅣB ,poorly differentiated tumor were independent prognostic factors of overall survival and disease-free survival of patients with T3 stage gallbladder cancer (all P<0.05).Three hundred and twenty-nine patients(79.3%) had high-risk clinicopathological subtypes,and the median survival time after curative resection with and without adjuvant therapy was 17 months and 34 months respectively,and the 3-year and 5-year overall survival rates were respectively 40.0%,21.3% and 46.0%,46.0% (χ2=4.042,P=0.044);the median disease-free survival time was 9 months and 13 months,and the 3-year and 5-year disease-free survival rates were 23.4%,13.6% and 30.2%,18.2% (χ2=0.992,P=0.319). Conclusions: Postoperative adjuvant therapy following radical surgery did not yield significant improvements in the overall survival and disease-free survival rates of patients diagnosed with T3 gallbladder cancer. However, it demonstrated a significant extension in the overall survival rate for patients presenting high-risk clinicopathological subtypes.

Distal pancreatectomy with celiac axis resection for pancreatic body cancer: a single center review of 89 consecutive cases

Objective: To investigate the clinical efficacy of distal pancreatectomy with celiac axis resection(DP-CAR). Methods: A total of 89 consecutive patients (50 males and 39 females) who were diagnosed with pancreatic body cancer and underwent DP-CAR in Pancreas Center,First Affiliated Hospital of Nanjing Medical University between September 2013 and June 2022 were retrospectively reviewed. There were 50 males and 39 females,with age(M(IQR)) of 63(12) years(range:43 to 81 years). Perioperative parameters,pathology results and follow-up data of these patients were analyzed,χ2 or Fisher's test for categorical data while the Wilcoxon test for quantitative data. Survival results were estimated by the Kaplan-Meier survival method. Results: Among 89 cases,cases combined with portal vein-superior mesenteric vein or organ resection accounted for 22.5% (20/89) and 42.7% (38/89),respectively. The operative time,blood loss and postoperative hospital stay were 270 (110) minutes,300 (300) ml and 13 (10) days,respectively. The overall morbidity rate was 67.4% (60/89) while the major morbidity was 11.2% (10/89). The increase rate in transient liver enzymes was 42.7% (38/89),3.4% (3/89) for liver failure,53.9% (48/89) for clinically relevant postoperative pancreatic fistula,1.1% (1/89) for bile leak,3.4% (3/89) for chylous leak of grade B and C,11.2% (10/89) for abdominal infection,9.0% (8/89) for postoperative hemorrhage of grade B and C,4.5% (4/89) for delayed gastric emptying,6.7% (6/89) for deep vein thrombosis,3.4% (3/89) for reoperation,4.5% (4/89)for hospital mortality,7.9% (7/89) for 90-day mortality. The pathological type was pancreatic cancer for all 89 cases and pancreatic ductal adenocarcinoma made up 92.1% (82/89). The tumor size was 4.8(2.0) cm, ranging from 1.5 to 12.0 cm. The number of lymph nodes harvested was 14 (13)(range:2 to 33),with a positive lymph node rate of 13.0% (24.0%). The resection R0 rate was 30.0% (24/80) and the R1 (<1 mm) rate was 58.8% (47/80). The median overall survival time was 21.3 months (95%CI: 15.6 to 24.3) and the median disease-free survival time was 19.1 months (95%CI: 11.7 to 25.1). The overall survival at 1-year and 2-year were 69.60% and 39.52%. The median survival time of 58 patients with adjuvant chemotherapy was 24.3 months (95%CI: 17.8 to 32.3) while that of 13 patients without any kind of adjuvant therapy was 8.4 months (95%CI: 7.3 to 22.3). Seven patients accepted neoadjuvant chemotherapy and there was no significant morbidity among them,with a resection rate of R0 of 5/7. Conclusion: DP-CAR is safe and feasible for selective cases,which could be more valuable in improving long-term survival when combined with (neo) adjuvant therapy.

Postoperative Radiotherapy to Abdominal and Pelvic Lymphatic Drainage Area for Stage III Epithelial Ovarian Cancer: A Sharp Tool to Prolong Disease-Free Survival Time

For patients with stage III epithelial ovarian cancer, there are limited studies on the effects of postoperative adjuvant radiotherapy (RT) after standard cytoreductive surgery (CRS) and full treatment of first-line adjuvant chemotherapy (CT). The aims of our study were to assess the therapeutic efficacy and toxicity of our special postoperative radiotherapy to abdominal and pelvic lymphatic drainage area for stage III epithelial ovarian cancer patients. We retrospectively collected patients with stage III epithelial ovarian cancer after CRS and full-course adjuvant chemotherapy. The CT+RT group patients were treated with intensity modulated radiotherapy (IMRT) to abdominal and pelvic lymphatic drainage area (which has been shown to be an alternative to whole abdominal radiotherapy (WART) both on the basis of clinical result and dosimetric verification from our prior study). The CT group data was obtained from the PUMCH's electronic medical record analytical database between 2010 and 2020. A propensity score matching analysis was performed 1:2 between CT+RT group and CT group. A total of 132 patients with median follow-up of 73.9 months (9.1-137.7 months) were included (44 and 88 for the CT+RT and CT groups, retrospectively). The baseline characteristics of age, histology, level of CA12-5, surgical staging, residual tumor, courses of adjuvant CT, and courses to reduce CA12-5 to normal were all balanced. The median disease-free survival (DFS) time, 5-year overall survival (OS), and local recurrence free survival (LRFS) of CT+RT group and CT group were 100.0 months versus 25.9 months (p = 0.020), 69.2% versus 49.9% (p = 0.002), 85.9% versus 50.5% (p = 0.020), respectively. Distant metastasis was still the primary reason (57.6%), and local failure rate was 42.3%, the local recurrence rate was significantly lower in CT+RT group, compared with CT group (13.6% versus 45.5%, p = 0.016). In terms of toxicity, CT+RT group mainly presented with acute hematological toxicities, with no statistically significant difference with CT group when compared with grade III intestinal adverse effects (3/44 versus 6/88, p = 0.480). This report demonstrates that long-term disease-free survival could be achieved in stage III epithelial ovarian cancer patients treated with IMRT preventive radiation to abdominal and pelvic lymphatic area. Compared with CT group, DFS and OS were significantly prolonged and adverse effects were acceptable.

Identification of LOX as a candidate prognostic biomarker in Glioblastoma multiforme

BackgroundGlioblastoma multiforme (GBM) is the most malignant type of glioma. GBM tumors grow rapidly, have a high degree of malignancy, and are characterized by a fast disease progression. Unfortunately, there is a lack of effective treatments. An effective strategy for the treatment of GBM would be to identify key biomarkers correlating with the occurrence and progression of GBM and developing these biomarkers into therapeutic targets. Method and ResultsIn this study, using integrated bioinformatics analysis, we identified differentially expressed genes (DEGs), including 130 genes that were upregulated in GBM compared to normal brain tissue, and 128 genes that were downregulated in GBM. Based on Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis, these genes were associated with regulation of tumor cell adhesion, differentiation, morphology in GBM and were mainly enriched in Complement and coagulation cascades pathway. The Search Tool for the Retrieval of Interacting Genes (STRING) database was used to construct a Protein-Protein Interaction network. Ten hub genes were identified, including FN1, CD44, MYC, CDK1, SERPINE1, COL3A1, COL1A2, LOX, POSTN and EZH2, all of which were significantly upregulated in GBM, these results were confirmed by oncomine database exploration. Alteration analysis of hub genes found that patients with alteration in at least one of the hub genes showed shorter median survival times (p = 0.013) and shorter median disease-free survival times (p = 2.488E-3) than patients without alterations in any of the hub genes. Multiple tests for survival analysis showed that among individual hub genes only expression of LOX was correlated with patient survival (P < 0.05).GDS4467 data set was used to analyze the expression of LOX in gliomas with different degrees of malignancy, and it was found that the expression level of LOX was positively correlated with the malignant degree of gliomas.By analyzing GDS 4535 data set showed that the expression level of LOX was positively correlated with the differentiation degree of GBM cells ConclusionThis research suggests that FN1, CD44, MYC, CDK1, SERPINE1, COL3A1, COL1A2, LOX, POSTN and EZH2 are key genes in GBM. However, only LOX is correlated with patient survival and promotes glioblastoma cell differentiation and tumor recurrence. LOX may be a candidate prognostic biomarker and potential therapeutic target for GBM.

Total Superior Mesenteric Artery Nerve Plexus Preservation During Pancreaticoduodenectomy for Pancreatic Cancer.

Superior mesenteric artery (SMA) nerve plexus (PLsma) dissection has been performed to achieve R0 resection in pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) in high-volume centers. However, full-extent PLsma preservation in PD is employed in our institution. The feasibility of the PLsma preservation strategy was investigated. Between January 2010 and December 2020, 156 patients underwent PLsma preservation PD for PDAC at our institution. Of these, 118 patients had resectable PDAC (R group) and 38 patients had borderline resectable artery (BR-A group). Clinical and oncological outcomes focusing on local recurrence, patient prognoses, and morbidities (including postoperative refractory diarrhea) were retrospectively analyzed and our postoperative outcomes were compared with those of other institutions. Pathological R0 resection by PLsma preservation PD was achieved in 96 R group patients (81.4%) and 27 BR-A group patients (71.1%). The median postoperative hospital stay was 15.0days in both groups. Local site-only recurrence was observed in 10.2% (12/118) of R-group and 10.5% (4/38) of BR-A-group patients, whereas distant site-only recurrence occurred in 21.2% (25/118) of R-group and 28.9% (11/38) of BR-A-group patients. Median survival times were 64.3months (R group) and 35.4months (BR-A group, p = 0.07). Median disease-free survival (DFS) times were 31.0months (R group) and 12.0months (BR-A group). No diarrhea requiring opioids was observed in either group. These results were equal or superior to those of PLsma dissection PD in other institutions. PLsma preservation in PD was feasible compared to PLsma dissection in recurrence and overall survival.

Impact of CSF3R Mutation on Treatment Response and Survival of Patients with Acute Myeloid Leukemia

To investigate the expression of CSF3R mutation in acute myeloid leukemia (AML) and analyze its clinical characteristics and prognosis. A retrospective study was conducted in 212 patients with AML who were newly diagnosed in the Second Hospital of Shanxi Medical University from January 1th 2018 to June 30th 2021, including 22 patients with CSF3R mutations as mutation group and 190 patients with CSF3R wild type ［66 cases of them were screened by propensity score matching (PSM), as control group］. The early efficacy and survival between the two groups were compared. The median age of patients in the mutation group was 50(17-73) years old, and the ratio of male to female was 1.2:1 The main types were AML with maturation (11 cases) and acute myelomonocytic leukemia (9 cases). Prognostic stratification was carried out according to the risk stratification system of the European leukemia network in 2017, with 16 cases (72.73%) in the middle and high-risk group. At the initial diagnosis, the median count of white blood cell (WBC) was 44.75(1.30-368.71)×109/L, among which 15 cases (68.18%) were >10×109/L, and the median count of platelet (PLT) was 24(4-55)×109/L. CSF3R T618I (68.18%) was a common mutation site, which had concomitant gene mutations, in which CEBPA mutation was the most common (10 cases, 45.45%), but only existed in CSF3R T618I mutation. The CR/CRi rate was 68.18% and 71.21% in the mutant group and the control group (P >0.05), the median over all survival time was 15 months and 9 months (P >0.05), and the median disease-free survival time was 8 months and 4 months (P >0.05), respectively. Most AML patients with CSF3R mutation are middle-aged patients, the main types are AML with maturation and acute myelomonocytic leukemia, and most of them have middle and high-risk prognosis. CSF3R mutation may not be an independent prognostic marker for newly diagnosed AML patients.

Ultra-radical surgery for advanced ovarian cancer: a retrospective cohort study in a tertiary referral cancer center in the UK.

Ovarian cancer is the leading cause of death from gynecological cancer in the UK. The standard of care is a combination of surgery and chemotherapy. The aim of the treatment is the resection of all macroscopic disease. In selected cases of advanced ovarian cancer this is achieved with ultra-radical surgery. However, NICE encourages further research due to low quality evidence on the safety and efficacy of this extensive surgery. The aim of this study was to examine the morbidity and survival rates of ultra-radical surgery for advanced ovarian cancer performed in our unit and compare our findings with the current literature. This is a retrospective study of 39 patients diagnosed with stage IIIA-IV ovarian and primary peritoneal cancer who underwent surgery in our unit between 2012 and 2020. The main outcome measures were the perioperative complications, the disease-free survival, the overall survival rate and the recurrence rate. The study enrolled 39 patients with stages IIIA-IV who were treated in our unit between 2012 and 2020. 21 patients were at stage III (53.8%) whereas 18 (46.1%) at stage IV. 14 patients underwent primary and 25 secondary debulking surgery. Major and minor complications occurred 17.9% and 56.4% of the patients, respectively. Complete cytoreduction following surgery was achieved in 24 cases (61.5%). The mean and the median survival time were 4.8 years and 5 years, respectively. The mean disease-free survival time was 2.9 years while median disease-free survival time was 2 years. Age (P=0.028) and complete cytoreduction (p=0.048) were found to be significantly associated with survival. Primary debulking surgery was significantly associated with lower probability of recurrence (P=0.049). Although the number of patients is relatively small, our study indicates that ultra-radical surgery in centers with high expertise may result in excellent survival rates with an acceptable rate of major complications. All patients in our cohort were operated by an accredited gynecological oncologist and a hepatobiliary general surgeon with a special interest in ovarian cancer. A few cases required input from a colorectal and a thoracic surgeon. We believe that the careful selection of the patients that can benefit from ultra-radical surgery and our model of joint surgery can explain our excellent results. Further research is essential to establish that ultra- radical surgery has an acceptable rate of morbidity for patients with advanced ovarian cancer.

Abstract HER2-04: HER2-04 Prevalence of HER2-low among Metastatic Breast Cancer Patients and Their Outcomes Compared to HER2 IHC 0

Abstract Prevalence of HER2-low among Metastatic Breast Cancer Patients and Their Outcomes Compared to HER2 IHC 0 Background: Amplification and/or overexpression of the HER2 gene is detected in approximately 15% to 20% of breast cancer (BC) patients. HER2-targeted therapies improve survival in HER2+ BC. Current HER2 diagnostic tests and thresholds were designed and optimized to predict benefit from HER2-directed therapies. The DESTINY-Breast04 trial demonstrated notable efficacy of HER2 antibody-drug conjugate trastuzumab deruxtecan, in patients whose tumors are not conventionally HER2+, but defined as HER2-low (IHC 1 or 2+ without HER2 amplification). A better understanding of the HER2-low phenotype is therefore of critical importance. Methods: Eligible pts were adults with metastatic HER2 IHC (0,1+,2+/FISH negative) BC seen at MD Anderson between 2006 and 2019. Primary biopsy of the breast was used to test biomarkers. HER2 low was defined as IHC 1+ or 2+ and FISH-negative. HER2-negative was defined as HER2 IHC 0. Multi-covariate logistic regression models were used to evaluate effect of clinical factors on HER2 low status and pCR. Overall survival (OS) was defined as time from diagnosis date until death. Disease free survival (DFS) was defined as time from definitive surgery date until the first local/distant recurrence or death from any cause. Patients alive without events (death for OS, recurrence/death for DFS) were censored at last follow-up date. OS and DFS times were estimated by Kaplan-Meier method. Multivariate Cox proportional hazards regression models were applied to assess effect of covariates of interest on OS and DFS. Results: A total of 3053 early stage and 1203 de novo female BC patients were included in the analysis. The prevalence of HER2 low for early stage patients was 59.3% (1811/3053) and for de novo metastatic disease 59.3% (713/1203). In early stage patients, white race, higher nuclear grade and positive ER status were significantly associated with HER2 low status in multicovariate logistic regression. Univariately, pCR rate was significantly associated with negative ER (10.2% in negative vs 2.7% in positive), negative PR (8.6% vs 2%) and negative lymphatic vascular invasion (9.2% vs 2%). Multicovariate logistic regression showed ER (p=0.0124), PR (p=0.0439) status and lymphatic vascular invasion (p&amp;lt; 0.0001) were significantly associated with pCR status. With median follow-up of 8.5 years, median OS time was 5.3 years (95% CI: [4.9, 5.4]), 5.4 years and 4.8 years in HER2 low and HER2 0 groups, respectively. In multicovariate Cox regression, HER2 low was significantly associated with longer OS (HR=0.87, p=0.008), adjusted for age, race, stage, nuclear grade, lymphatic-vascular invasion and ER/PR status. In patients who received neoadjuvant chemotherapy, adjusted for stage, nuclear grade, ER and PR status and pCR, HER2 low was significantly associated with a longer OS time (HR=0.87, p=0.04). Median DFS time was 1.9 years (95% CI: (1.8, 2.0)). Age, stage, histology, nuclear grade, and ER and PR status were significantly associated with DFS by multicovariate Cox regression. Among de novo cases, higher nuclear grade (HR [II vs I]=1.838, p =0.008; HR [III vs I]=1.856, p=0.007) and positive ER status (OR=1.933, p &amp;lt;.0001) were associated with high percentage of HER2 low by multicovariate logistic regression. Median OS time was 3.2 years (95% CI: (3.0, 3.5)). By multicovariate Cox regression, race, histology, nuclear grade, ER and PR status, and HER2 low status (HR=0.834, p=0.0260) were significantly associated with OS time. Conclusions: In metastatic BC pts, HER2 low status was significantly associated with a longer OS and DFS when compared to HER2 0. Nuclear grade and ER positivity was significantly associated with HER2 low status. Biomarkers on recurrence tumor will be presented. This real world data helps to establish the prevalence of HER2 low and their outcomes for this selective cohort. Citation Format: Akshara Singareeka Raghavendra, Diane Liu, Jason Mouabbi, Debu Tripathy. HER2-04 Prevalence of HER2-low among Metastatic Breast Cancer Patients and Their Outcomes Compared to HER2 IHC 0 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr HER2-04.

Clinical features and prognosis of patients who undergo renal transplant with urothelial carcinoma.

527 Background: Malignant tumor has been identified as one of the three major causes of death for kidney transplant recipients. This study collected the clinical data of UC patients after kidney transplantation in our center retrospectively, and explored the natural course of disease and response to systemic treatment of this special subgroup of patients. Methods: 1332 consecutive uc patients diagnosed pathologically in our department from 2012 to 2022 were collected, including 26 renal transplant pts. Data were collected, including gender, age, pathological grade, primary site, initial diagnosis stage, metastasis time, site, systemic treatment plan and response to treatment. Kaplan-Meier survival analysis was used to explore the survival and prognostic factors of uc patients after renal transplantation. Results: 1332 consecutive uc patients from Sep 2012 to Sep 2022 in our department were collected, including 26 pts (1.95%) after renal transplantation. 7 males (26.9%).，overall median age of diagnosis 59.0y (40-79y), 24 pathological high-grade (92.3%), 6 cases are with other differentiation (23%), 7 cases (63.65%) her2 IHC 2~3+ in 11 tested cases. Primary site includes 8 renal pelvis (30.8%), 7 ureter (26.9%), 3 bladder (11.5%) and 8 multiple (30.8%). T1, T2, T3, T4 and Tx accounted for 1 (3.8%), 8 (30.8%), 14 (53.8%), 0 and 3 (11.6%)，with lymph node metastasis in 2 (7.7%). Initial stage I, II, III and IV were 3.8%, 69.2%, 11.6% and 15.4% The median survival time of the four groups was 73.4, 38.0, 18.3 and 13.9 months respectively. The median disease-free survival time of 24 patients after radical surgery was 16.0 months (95% CI: 13.2-27.8m), and 11 patients (42.3%) relapsed within one year after surgery. Among systematic treatment, 24, 9 and 3 patients received the first-, second- and third line treatment. First-line includes nab-ptx+gem (7), ptx+gem+endo/bev (6), ptx+gem+cisplatin+endo/bev (4), gem+cisplatin (3), ADC (2 ), gem+carboplatin (1) and gem+oxa (1). Second-line includes nab-ptx based chemo (5), ADC (2), ptx+gem+cisplatin+endo (1) and ptx+sorafenib (1). Third-line includes nab-ptx +gem+cisplatin+bev (1), gem+cisplatin+sotan (1) and everolimus+cisplatin (1). The mPFS of first-, second-, and third-line were 6.5 months (95% CI: 6.4-17.7 m), 2.6 months (95% CI: 1.6-5.3 m) and 2.0 months (95% CI: 1.8-21 m). The mOS was 15.3 months (95% CI: 8.4-15.1 m), 11.6 months (95% CI: 5.0-16.3 m) and 8.0 months (95% CI: 1.6-13.0 m). The most common distant metastasis in late stage included lymph node in 16 cases (61.5%), lung in 12 cases (46.1%), bone in 7 cases (26.9%) and liver in 5 cases (19.2%). Conclusions: Urothelial carcinoma in renal transplant patients has higher degree of malignancy, nearly half of the patients have rapid recurrence and metastasis after operation. It seems these sub-group patients have higher her2 (IHC 2-3+) status.

JGOG2046: a feasibility study of neoadjuvant chemotherapy followed by debulking surgery for clinically diagnosed FIGO stage IVb endometrial cancer.

We evaluated the feasibility of neoadjuvant chemotherapy, followed by debulking surgery, for clinically diagnosed FIGO stage IVb endometrial cancer (protocol number: JGOG2046). The experimental treatment consisted of 3 cycles of paclitaxel (180mg/m2) plus carboplatin (AUC5) followed by debulking surgery, including total abdominal hysterectomy, bilateral salpingo-oophorectomy, and 3 cycles of adjuvant chemotherapy. Patients were considered as eligible if they were pathologically diagnosed as primary endometrial cancer, and had both endometrial tumor and distant metastasis confirmed by imaging examinations. The primary endpoint was the incidence of patients who completed debulking surgery after the neoadjuvant chemotherapy. While 51 patients were enrolled from 23 hospitals, the final study cohort consisted of 49 patients with a mean age of 59.0years. Although the response ratio of the neoadjuvant chemotherapy was 65.3% (95% CI 50.4-78.3%), 67.3% (95% confidence interval (CI) 52.5-80.1%) underwent debulking surgery after the neoadjuvant chemotherapy and 59.2% (95% CI 45.2-71.8%) completed the protocol treatment including 3 courses of adjuvant chemotherapy. The median disease-free survival time was 9.1months (95% CI 6.5-11.9), while the median overall survival time was 23.2months (95% CI 11.9-27.8). A patient with sigmoid colon cancer and another with cervical cancer were included in this study. Neoadjuvant chemotherapy followed by debulking surgery was a feasible and acceptable treatment for metastatic endometrial cancer. (225 words).

Survival impact of unexpected N2 in stage IIIB/N2 non-small cell lung cancer patients.

We investigated the effect of unexpected N2 on survival in stage IIIB/N2 cases. We retrospectively analyzed 1803 non-small cell lung cancer patients between 2010 and 2016. There were 89 patients (4.9%) with unexpected N2 (pathological (p) IIIB/N2 group), whereas 49 patients (2.7%) with cN2 (clinical (c) IIIB/N2 group). Although pIIIB/N2 group underwent surgery followed by adjuvant therapy, the cIIIB/N2 group of patients had multimodality treatment including induction chemotherapy ± radiotherapy followed by surgery. The five-year overall survival (OS) for all patients was 36.0% [median survival time (MST) 27.9 months], and disease-free survival (DFS) was 28.9% (MST, 18.2 months). The OS was 39.6% (MST: 34.4 months) and the median DFS time was 31.1% (Median: 23.1 months) in the pIIIB/N2 group, whereas it was 29.2% (MST: 23.0 months) for OS and 22% (median: 12.4 months) for DFS in the cIIIB/N2 group. There were no significant OS and DFS differences between the pIIIB/N2 group and the cIIIB/N2 group (p = 0.124 and p = 0.168, respectively). In stage IIIB/N2 cases, the fact that N2 could not be detected preoperatively with minimally invasive or invasive methods and was detected in the pathological examination after surgery does not provide a survival advantage.

Hepatic artery lymph node relevance in periampullary tumors: A retrospective analysis of survival outcomes.

The Periampullary area comprehends a heterogeneous and complex structure with different histological tissues. Surgical standards include the peripancreatic regional lymphadenectomy, and during pancreatoduodenectomy (PD) the hepatic artery lymph node HALN(8a) is dissected. We aimed to describe the prognostic significance of the HALN(8a) lymph node metastasis in terms of disease-free survival (DFS) and overall survival (OS) in a specific cohort of patients in limited economic and social conditions. A retrospective study was conducted based on a prospective database from the HPB department of patients who underwent pancreaticoduodenectomy (PD) due to periampullary tumors during 2014-2021. Overall survival (OS) and disease-free survival (DFS) were estimated to be associated with positive HALN(8a) using Kaplan-Meier analysis. Log Rank test and Cox proportional hazards regression analysis was used. 111 patients were included, 55,4% female. The most frequent pathology was ductal adenocarcinoma (60.3%). The positive rate of the HALN(8a) node was 21.62%. The Median OS time was 25.5 months, and the median DFS time was 13,8 months. Positive HLAN(8a) node, the cutoff of lymph node ratio resection (LNRR), and vascular invasion showed a strong association with OS. (CoxRegression p = 0.03 HR 0.5, p 0.003 HR = 1.8, p = 0.02 HR 0.4 CI 95%). In terms of DFS, lymph node ratio cutoff, tumoral size, and vascular invasion showed a statistically significant association with the outcome (p = 0.008, HR = 1.5; p = 0.04 HR = 2.1; p = 0.02 HR = 0.4 CI 95%). In this series of PD, OS was reduced in patients with HALN(8a) compromise in patients with pancreatic cancer, however without statistical significance in DFS. In multivariate analysis, lymph node status remains an independent predictor of OS and DFS. Further studies are needed.

Adjuvant Radiotherapy Improves Survival for T1b Superficial Esophageal Cancer with Lymphovascular Invasion after Endoscopic Resection

<h3>Purpose/Objective(s)</h3> Several studies, including the multicenter prospective trial JCOG 0508, have reported a higher risk of recurrence in patients with pT1b esophageal carcinoma (EC) with lymphovascular invasion (LVI) after endoscopic resection (ER). The role of adjuvant radiotherapy in this population has not been fully proven. Thus, the aim of this study was to investigate the effectiveness of adjuvant radiotherapy for T1b EC with LVI. <h3>Materials/Methods</h3> This was a multicenter retrospective study including 6 centers in China. From May 2011 to March 2019, patients with T1b EC and LVI who underwent ER with or without radiotherapy were included and analyzed. The overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan-Meier method, and the log-rank test was used to analyze differences between the groups. Factors between different groups were compared using chi square test. <h3>Results</h3> A total of 42 patients were included, including 37 (88.1%) males and 5 (11.9%) females. The median age was 60 (49-80) years old. Forty (95.2%) patients were squamous cell carcinoma, and two (4.8%) were adenosquamous cell carcinoma. The number of patients with tumor of SM1 and SM2 invasion were 10 (23.8%) and 32 (76.2%), respectively. The median lesion length was 3.0 cm. Thirty-six (85.7%) Patients underwent complete ER and six (14.3%) patients were with R1 resection. Sixteen (38.1%) patients received adjuvant radiotherapy, including two received chemoradiotherapy. The factors mentioned above were well balanced between radiotherapy and non-radiotherapy groups. The median survival in the radiotherapy vs. non-radiotherapy groups were not reached vs. 80.4 months, respectively. The 3y- and 5y-OS were 91.7% and 91.7% in the radiotherapy group vs. 80.8% and 58.9% in the non-radiotherapy group, respectively (p=0.045). The median DFS time in the radiotherapy vs. non-radiotherapy groups was not reached vs. 43.8 months, respectively. The 3y- and 5y-DFS were 92.9% and 92.9% in the radiotherapy group vs. 69.2% and 43.5% in the non-radiotherapy group, respectively (p=0.011). Radiotherapy was the only prognostic factor for both OS and DFS. <h3>Conclusion</h3> Adjuvant radiotherapy improved the survival of patients with T1b EC with LVI after ER. This combined treatment strategy could cure T1b-LVI EC while preserving the esophagus.

The value of contrast-enhanced ultrasound quantitative parameters in the prognosis prediction of hepatocellular carcinoma after thermal ablation: a retrospective cohort study.

The postoperative recurrence rate is the main factor affecting the prognosis of hepatocellular carcinoma (HCC) patients, this study sought to investigate the value of contrast-enhanced ultrasound (CEUS) quantitative parameters in predicting the recurrence and the survival of HCC patients after thermal ablation. The data of 97 patients with pathologically diagnosed HCC who underwent thermal ablation were retrospectively included in this study. The patients had an average age of 46.6 years (range, 23-79 years), and 79 were male and 18 were female. CEUS follow-up was performed at 1- and 3-month after thermal ablation, then at 6-month intervals thereafter for 5 years. CEUS was performed before thermal ablation, and the results were analyzed quantitatively using CEUS perfusion software (VueBox®, Bracco, Italy). The ratios of the CEUS quantitative parameters between the HCC lesions and reference liver parenchyma were calculated. The parameters included the average contrast signal intensity (MeanLin), peak enhancement (PE), rising time (RT), fall time (FT), time to peak (TTP), mean transit time (mTT), perfusion index (PI), Wash-in Area Under the Curve (WiAUC), Wash-in Rate (WiR), Wash-in Perfusion Index (WiPI), Wash-out Area Under the Curve (WoAUC), Wash-out Rate (WoR), and WiAUC + WoAUC (WiWoAUC). The correlations between the preoperative CEUS quantitative parameter ratios, the blood laboratory indexes, postoperative recurrence, and survival were analyzed using log-rank tests and a Cox regression model. The average follow-up duration period was 79 months (range, 5-145 months). The average recurrence time after ablation was 1-127 months, and the median disease-free survival time was 21 months. The 1-, 3- and 5-year survival rates were 96.9%, 92.3%, and 80.6%, respectively. The log-rank tests showed that tumor size, prothrombin time, and WiAUC, WoAUC, and WiWoAUC ratios were predictors of survival, and aspartate aminotransferase was a predictor of recurrence. The Cox regression analysis showed that tumor size [odds ratio (OR): 6.421; 95% CI: 1.434-28.761] and alanine transaminase (OR: 0.88; 95% CI: 0.010-0.742) were predictors of a poor prognosis. CEUS quantitative parameters before thermal ablation and blood laboratory indexes provide potential clinical value for predicting the postoperative recurrence and survival of HCC patients.

Stereotactic Body Radiation Therapy for Lung Metastases From Sarcoma in Oligometastatic Patients: A Phase 2 Study

The lung is the most frequent site of metastasis in patients with sarcoma. Pulmonary metastasectomy is the most common treatment performed. Stereotactic body radiation therapy (SBRT) has proven to be a potential alternative to resection. This prospective phase 2 study aimed to assess the role of SBRT for patients with lung metastases. Adult patients with up to 4 lung metastases (LMs) ≤5 cm in diameter and unsuitable for surgery were included. Dose prescription was based on site and size: 30 Gy/1 fraction for peripheral lesions ≤10 mm, 60 Gy/3 fractions for peripheral lesions 11 to 20 mm, 48 Gy/4 fractions for peripheral lesions >20 mm, and 60 Gy/8 fractions for central lesions. The primary endpoint was the proportion of treated lesions free from progression at 12 months. Secondary endpoints were disease-free survival (DFS), overall survival (OS), and toxicity. Between March 2015 and December 2020, 44 patients with a total of 71 LMs were enrolled. Twelve-month local control was 98.5% ± 1.4%, reaching the primary aim; the median DFS time was 12 months (95% CI, 8-16 months), and the 1-, 2-, 3-, 4-, and 5-year PFS rates were 50% ± 7.5%, 19.5% ± 6.6%, 11.7% ± 5.8%, 11.7% ± 5.8%, and 11.7% ± 5.8%, respectively. The median OS time was 49 months (95% CI, 24-49 months), and the 1-, 2-, 3-, 4-, and 5-year OS rates were 88.6% ± 4.7%, 66.7 ± 7.6%, 56.8% ± 8.4%, 53.0% ± 8.6%, and 48.2% ± 9.1%, respectively. Prognostic factors recorded as significantly affecting survival were age, grade of primary sarcoma, interval time from diagnosis to occurrence of LMs, and number of LMs. No severe pulmonary toxicity (grade 3-4) occurred. The study found a local control of LMs in almost all patients treated, with negligible toxicity. Survival was also highly satisfactory. Well-designed randomized trials comparing surgery with SBRT for patients with metastatic lung sarcoma are needed to confirm these preliminary data.