Survival with Cemiplimab in Recurrent Cervical Cancer.

BACKGROUND: Patients with recurrent cervical cancer have a poor prognosis. Cemiplimab, the fully human programmed cell death 1 (PD-1)-blocking antibody approved to treat lung and skin cancers, has been shown to have preliminary clinical activity in this population. METHODS: In this phase 3 trial, we enrolled patients who had disease progression after first-line platinum-containing chemotherapy, regardless of their programmed cell death ligand 1 (PD-L1) status. Women were randomly assigned (1:1) to receive cemiplimab (350 mg every 3 weeks) or the investigator's choice of single-agent chemotherapy. The primary end point was overall survival. Progression-free survival and safety were also assessed. RESULTS: A total of 608 women were enrolled (304 in each group). In the overall trial population, median overall survival was longer in the cemiplimab group than in the chemotherapy group (12.0 months vs. 8.5 months; hazard ratio for death, 0.69; 95% confidence interval [CI], 0.56 to 0.84; two-sided P<0.001). The overall survival benefit was consistent in both histologic subgroups (squamous-cell carcinoma and adenocarcinoma [including adenosquamous carcinoma]). Progression-free survival was also longer in the cemiplimab group than in the chemotherapy group in the overall population (hazard ratio for disease progression or death, 0.75; 95% CI, 0.63 to 0.89; two-sided P<0.001). In the overall population, an objective response occurred in 16.4% (95% CI, 12.5 to 21.1) of the patients in the cemiplimab group, as compared with 6.3% (95% CI, 3.8 to 9.6) in the chemotherapy group. An objective response occurred in 18% (95% CI, 11 to 28) of the cemiplimab-treated patients with PD-L1 expression greater than or equal to 1% and in 11% (95% CI, 4 to 25) of those with PD-L1 expression of less than 1%. Overall, grade 3 or higher adverse events occurred in 45.0% of the patients who received cemiplimab and in 53.4% of those who received chemotherapy. CONCLUSIONS: Survival was significantly longer with cemiplimab than with single-agent chemotherapy among patients with recurrent cervical cancer after first-line platinum-containing chemotherapy. (Funded by Regeneron Pharmaceuticals and Sanofi; EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 ClinicalTrials.gov number, NCT03257267.).

Open vs minimally invasive radical trachelectomy in early-stage cervical cancer: International Radical Trachelectomy Assessment Study.

BACKGROUND: Minimally invasive radical trachelectomy has emerged as an alternative to open radical hysterectomy for patients with early-stage cervical cancer desiring future fertility. Recent data suggest worse oncologic outcomes after minimally invasive radical hysterectomy than after open radical hysterectomy in stage I cervical cancer. OBJECTIVE: We aimed to compare 4.5-year disease-free survival after open vs minimally invasive radical trachelectomy. STUDY DESIGN: This was a collaborative, international retrospective study (International Radical Trachelectomy Assessment Study) of patients treated during 2005-2017 at 18 centers in 12 countries. Eligible patients had squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma; had a preoperative tumor size of ≤2 cm; and underwent open or minimally invasive (robotic or laparoscopic) radical trachelectomy with nodal assessment (pelvic lymphadenectomy and/or sentinel lymph node biopsy). The exclusion criteria included neoadjuvant chemotherapy or preoperative pelvic radiotherapy, previous lymphadenectomy or pelvic retroperitoneal surgery, pregnancy, stage IA1 disease with lymphovascular space invasion, aborted trachelectomy (conversion to radical hysterectomy), or vaginal approach. Surgical approach, indication, and adjuvant therapy regimen were at the discretion of the treating institution. A total of 715 patients were entered into the study database. However, 69 patients were excluded, leaving 646 in the analysis. Endpoints were the 4.5-year disease-free survival rate (primary), 4.5-year overall survival rate (secondary), and recurrence rate (secondary). Kaplan-Meier methods were used to estimate disease-free survival and overall survival. A post hoc weighted analysis was performed, comparing the recurrence rates between surgical approaches, with open surgery being considered as standard and minimally invasive surgery as experimental. RESULTS: Of 646 patients, 358 underwent open surgery, and 288 underwent minimally invasive surgery. The median (range) patient age was 32 (20-42) years for open surgery vs 31 (18-45) years for minimally invasive surgery (P=.11). Median (range) pathologic tumor size was 15 (0-31) mm for open surgery and 12 (0.8-40) mm for minimally invasive surgery (P=.33). The rates of pelvic nodal involvement were 5.3% (19 of 358 patients) for open surgery and 4.9% (14 of 288 patients) for minimally invasive surgery (P=.81). Median (range) follow-up time was 5.5 (0.20-16.70) years for open surgery and 3.1 years (0.02-11.10) years for minimally invasive surgery (P<.001). At 4.5 years, 17 of 358 patients (4.7%) with open surgery and 18 of 288 patients (6.2%) with minimally invasive surgery had recurrence (P=.40). The 4.5-year disease-free survival rates were 94.3% (95% confidence interval, 91.6-97.0) for open surgery and 91.5% (95% confidence interval, 87.6-95.6) for minimally invasive surgery (log-rank P=.37). Post hoc propensity score analysis of recurrence risk showed no difference between surgical approaches (P=.42). At 4.5 years, there were 6 disease-related deaths (open surgery, 3; minimally invasive surgery, 3) (log-rank P=.49). The 4.5-year overall survival rates were 99.2% (95% confidence interval, 97.6-99.7) for open surgery and 99.0% (95% confidence interval, 79.0-99.8) for minimally invasive surgery. CONCLUSION: The 4.5-year disease-free survival rates did not differ between open radical trachelectomy and minimally invasive radical trachelectomy. However, recurrence rates in each group were low. Ongoing prospective studies of conservative management of early-stage cervical cancer may help guide future management.

Adenosquamous cancer of the pancreas: A multicenter retrospective study.

INTRODUCTION: Adenosquamous cancer 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. METHODS: Multicenter retrospective observational study carried out at three Spanish hospitals. The study period was: January 2010-August 2020. A descriptive analysis of the data was performed, as well as an analysis of global and disease-free survival using the Kaplan-Meier statistic. RESULTS: Of a total of 668 pancreatic cancers treated surgically, twelve were ASCP (1.8%). Patient mean age was 69.2±7.4 years. Male/female ratio was 1:1. The main symptom was jaundice (seven patients). Correct preoperative diagnosis was obtained in only two patients. Nine pancreatoduodenectomies and three distal pancreatosplenectomies were performed. 25% had major complications. Mean tumor size was 48.6±19.4mm. Nine patients received adjuvant chemotherapy. Median survival time was 5.9 months, and median disease-free survival was 4.6 months. 90% of patients presented recurrence. Ten of the twelve patients in the study (83.3%) died, with disease progression being the cause in eight. Of the two surviving patients, one is disease-free and the other has liver metastases. CONCLUSION: ASCP is a very rare pancreatic tumor with aggressive behavior. It is rarely diagnosed preoperatively. The best treatment, if feasible, is surgery followed by the standard chemotherapy regimens for pancreatic adenocarcinoma.

Post-recurrence survival in patients with cervical cancer.

BACKGROUND: Up to 26% of patients with early-stage cervical cancer experience relapse after primary surgery. However, little is known about which factors influence prognosis following disease recurrence. Therefore, our aims were to determine post-recurrence disease-specific survival (PR-DSS) and to identify respective prognostic factors for PR-DSS. METHODS: Data from 528 patients with early-stage cervical cancer who relapsed after primary surgery performed between 2007 and 2016 were obtained from the SCANN study (Surveillance in Cervical CANcer). Factors related to the primary disease and recurrence were combined in a multivariable Cox proportional hazards model to predict PR-DSS. RESULTS: The 5-year PR-DSS was 39.1% (95% confidence interval [CI] 22.7%-44.5%), median disease-free interval between primary surgery and recurrence (DFI1) was 1.5 years, and median survival after recurrence was 2.5 years. Six significant variables were identified in the multivariable analysis and were used to construct the prognostic model. Two were related to primary treatment (largest tumour size and lymphovascular space invasion) and four to recurrence (DFI1, age at recurrence, presence of symptoms, and recurrence type). The C-statistic after 10-fold cross-validation of prognostic model reached 0.701 (95% CI 0.675-0.727). Three risk-groups with significantly differing prognoses were identified, with 5-year PR-DSS rates of 81.8%, 44.6%, and 12.7%. CONCLUSIONS: We developed the robust model of PR-DSS to stratify patients with relapsed cervical cancer according to risk profiles using six routinely recorded prognostic markers. The model can be utilised in clinical practice to aid decision-making on the strategy of recurrence management, and to better inform the patients.

Parallel-Group Controlled Trial of Surgery Versus Chemoradiotherapy in Patients With Stage I Esophageal Squamous Cell Carcinoma.

BACKGROUND & AIMS: Surgery is the standard of care for T1bN0M0 esophageal squamous cell carcinoma (ESCC), whereas chemoradiotherapy (CRT) is a treatment option. This trial aimed to investigate the noninferiority of CRT relative to surgery for T1bN0M0 ESCC. METHODS: Clinical T1bN0M0 ESCC patients were eligible for enrollment in this prospective nonrandomized controlled study of surgery versus CRT. The primary endpoint was overall survival, which was determined using inverse probability weighting with propensity scoring. Surgery consisted of an esophagectomy with 2- or 3-field lymph node dissection. CRT consisted of 2 courses of 5-fluorouracil (700 mg/m2) on days 1-4 and cisplatin (70 mg/m2) on day 1 every 4 weeks with concurrent radiation (60 Gy). RESULTS: From December 20, 2006 to February 5, 2013, a total of 368 patients were enrolled in the nonrandomized portion of the study. The patient characteristics in surgery arm and CRT arm, respectively, were as follows: median age, 62 and 65 years; proportion of males, 82.8% and 88.1%; and proportion of performance status 0, 99.5% and 98.1%. Comparisons were made using the nonrandomized groups. The 5-year overall survival rate was 86.5% in the surgery arm and 85.5% in the CRT arm (adjusted hazard ratio, 1.05; 95% confidence interval, 0.67-1.64 [<1.78]). The complete response rate in the CRT arm was 87.3% (95% confidence interval, 81.1-92.1). The 5-year progression-free survival rate was 81.7% in the surgery arm and 71.6% in the CRT arm. Treatment-related deaths occurred in 2 patients in the surgery arm and none in the CRT arm. CONCLUSIONS: CRT is noninferior to surgery and should be considered for the treatment of T1bN0M0 ESCC.

A novel nomogram with preferable capability in predicting the overall survival of patients after radical esophageal cancer resection based on accessible clinical indicators: A comparison with AJCC staging.

BACKGROUND: Esophageal cancer (EC) is a malignant tumor with high mortality. Nomogram is an important tool used in clinical prognostic assessment. We aimed to establish a novel nomogram to predict the overall survival (OS) of EC patients after radical esophagectomy. METHODS: Data pertaining to the survival, demography, and clinicopathology of 311 EC patients who underwent radical esophagectomy were retrospectively investigated. The nomogram was established based on Cox hazard regression analysis. The calibration curves and Harrell's concordance index (C-index) were used to verify the predictive accuracy and ROC curves were used to assess the efficacy of the nomogram. Kaplan-Meier curves showed the prognostic value of the related risk classification system. Pearson correlation test was performed to determine the correlation between the risk classification system and TNM staging. RESULTS: The median OS and 5-year survival rates in the primary and validation cohorts were 44 months and 29.8%, and 52 months and 27.1%, respectively. We used six independent prognostic factors-age, Sex, AGR, PRL, N stage, and PNI-in the nomogram. The C-index of nomogram was 0.75 and 0.70 in the primary and validation cohorts, respectively. Calibration curves indicated high consistency between actual and predicted OS. ROC curves showed that nomogram has a better efficacy compared with TNM staging in both cohorts. Patients were divided into three risk groups according to the total nomogram score, the median OS in each group was significantly different in both cohorts. Furthermore, the risk classification system was strongly correlated with the T and N staging system and exhibited a better OS prediction capability. CONCLUSIONS: We established a novel and practical nomogram with a subordinate risk classification system to predict the OS of patients after radical esophagectomy. Compared with AJCC staging, this nomogram had preferable clinical capability in terms of individual prognosis assessment.

The 5-year overall survival of cervical cancer in stage IIIC-r was little different to stage I and II: a retrospective analysis from a single center.

BACKGROUND: The 2018 International Federation of Gynecology and Obstetrics (FIGO) staging guideline for cervical cancer includes stage IIIC recognized by preoperative radiology (IIIC-r) to state there are lymph nodes metastases (LNM) identified by imaging tools. We aim to explore the reasonability and limitations of stage IIIC-r and try to explore the potential reasons. METHODS: Electronic medical records were used to identify patients with cervical cancer. According to the new staging guidelines, patients were reclassified and assigned into five cohorts: stage I, stage II, stage IIIC-r, LNM confirmed by pathology (IIIC-p) and LNM detected by radiology and confirmed by pathology (IIIC r + p). Five-year overall survivals were estimated for each cohort. The diagnosis accuracy of computed tomography (CT), magnetic resonance imaging (MRI) and diameter of detected lymph nodes were also evaluated. RESULTS: A total of 619 patients were identified. The mean follow-up months were 65 months (95% CI 64.43-65.77) for all patients. By comparison, the 5-year overall survival rates were not statistically different (p = 0.21) among stage IIIC-r, stage I and stage II. While, the rates were both statistical different (p<0.001) among stage IIIC-p, IIIC r + p and stage I and stage II. The sensitivities of CT and MRI in detecting LNM preoperatively were 51.2 and 48.8%. The mean maximum diameter of pelvic lymph nodes detected by CT cohort was 1.2 cm in IIIC-r cohort, and was 1.3 cm in IIIC r + p cohort. While, the mean maximum diameter of pelvic lymph nodes detected by MRI was 1.2 cm in IIIC-r cohort, and was 1.48 cm in IIIC r + p cohort. When the diagnosis efficacy of the diameter of pelvic lymph nodes in detecting LNM were evaluated, the area under the receiver operating characteristic curve (ROC curve) was 0.58 (p = 0.05). CONCLUSIONS: It seems that the FIGO 2018 staging guideline for cervical cancer is likely to has certain limitations for the classification of those with LNM. CT or MRI, however, has limitations on detecting LNM. It would be better to use more accurate imaging tools to identify LNM in the clinical practices.

Clinical presentation and prognosis of adenosquamous carcinoma of the pancreas - Matched-pair analysis with pancreatic ductal adenocarcinoma.

INTRODUCTION: Adenosquamous carcinoma of the pancreas (ASCP) is a rare subtype of pancreatic adenocarcinoma. The aim of this study was to investigate the characteristics and outcomes of ASCP in comparison to pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: All patients with ASCP treated between December 2001 and December 2017 were identified from a prospective database. Clinicopathological and follow-up data were analyzed. A nested case-control-study with matched-pair analysis was performed to compare overall survival of ASCP and PDAC. RESULTS: Of 4009 patients undergoing surgery for pancreatic adenocarcinoma 91 patients had ASCP. Compared to PDAC ASCP were larger (4.0 vs. 3.2 cm; p < 0.0001), more frequently involved lymph nodes (88% vs. 78%; p = 0.0216), more frequently showed poor differentiation (G3: 79% vs. 36%; p < 0.0001) and more frequently were located in the pancreatic tail (19% vs. 10%; p = 0.0179). Overall median post-resection-survival was shorter in ASCP (10.8 vs. 20.5 months in PDAC; p = 0.0085), but 5-year survival rates were comparable (18.2% vs. 17.5%). After matching for the unevenly distributed prognostic factors survival after resection of ASCP and PDAC was comparable (p = 0.8301). Localization in the head or several parts of the pancreas, high CA 19-9 levels, and M1 disease were independent predictors of survival in patients with ASCP. CONCLUSION: ASCP is more aggressive with poorer differentiation and higher rates of lymph node metastases compared to PDAC. In spite of a shorter median survival, 5-year survival rates after surgical resection of about 18% can be expected in ASCP and support resection as part of a multimodal therapy as the treatment of choice in this rare cancer.

Adenosquamous carcinoma of the breast: a population-based study.

BACKGROUND: To summarize the clinicopathological characteristics, prognosis, and management of breast adenosquamous carcinoma (ASC). METHODS: A population-based study was performed using retrospectively extracted data from the Surveillance, Epidemiology, and End Results database for breast cancer patients with histological diagnoses of ASC, infiltrating duct carcinoma (IDC) and squamous cell carcinoma (SCC) from 2004 to 2016. RESULTS: ASC presented similar tumor size but low histological grade and less lymph node metastasis compared to IDC. ASC expressed less positive rate of hormone receptors and barely HER2, which was similar with SCC. ASC patients underwent the similar surgical and systematic treatment as IDC, only with less radiotherapy. Median follow-up data of 78 months showed that the prognosis of IDC patients was better than that of ASC patients (all p < 0.05 for BCSM and OS). ASC was not an independent prognosis factor of breast cancer. After propensity score matching (PSM), no significant difference in BCSM nor OS was observed between ASC and IDC groups. In HR-negative patients, the prognosis of ASC was similar with that of IDC, and both were superior to SCC. In HR-positive patients, the 5-year survival rate of ASC was 63.5%, which was far less than that in ASC of HR-negative (81.0%). Multivariate analysis showed that older age (age > 60) and advanced AJCC-stage were independent factors of poor prognosis in ASC, breast-conserving surgery was also ideally suited for ASC. CONCLUSIONS: ASC has unique clinicopathological characteristics and prognosis. It is imperative to focus on a more precise and personalized treatment management of ASC patients.

Analysis of clinical characteristics and prognosis with cervical adenosquamous carcinoma: a large population-based study.

Objective: The target of this work was to analyze the clinical characteristics and construct nomograms to predict prognosis in patients with cervical adenosquamous carcinoma (ASC). Methods: A total of 788 ASC patients were tracked in the Surveillance, Epidemiology and End Results database. We compared the clinical characteristics and prognostic factors of ASC. Cox regression models were established, and nomograms were constructed and verified. Results: ASC patients have lower age levels and higher histological grades than patients with squamous cell carcinoma. Nomograms were constructed with good consistency and feasibility in clinical practice. The C-indices for overall survival and cancer-specific survival were 0.783 and 0.787, respectively. Conclusion: ASC patients have unique clinicopathological and prognostic characteristics. Nomograms were successfully constructed and verified.

Glassy cell carcinoma of the uterine cervix: 20-year experience from a comprehensive cancer center.

PURPOSE: Glassy cell carcinoma (GCC) of the uterine cervix is a rare entity. This study aims at describing the clinical characteristics and outcomes of cervical GCC patients treated in a comprehensive cancer center. MATERIAL AND METHODS: We retrospectively reported patients and tumors characteristics, therapeutic management, overall survival (OS), progression-free progression (PFS), relapse rates, and toxicities. RESULTS: Between 1994 and 2014, 55 patients were treated with curative intent. The median age at diagnosis was 41 years (range, 20-68). Among 22 patients with early stage tumors (IA2-IB1-IIA1), 17 had preoperative brachytherapy, followed by radical hysterectomy. Among 33 patients with locally advanced disease (≥IB2), 32 underwent chemoradiation±brachytherapy boost. After a median follow-up of 5.4 years (range, 0.15-21.7 years), 18/55 (33%) patients experienced tumor relapse. Local recurrence occurred in 2/22 (9%) patients with early disease (treated with upfront surgery) and in 3/32 (9%) patients with locally advanced disease. Most frequent relapses were distant, occurring in a total of 11/55 patients (20%). PFS rates at 5-year were 86.4% (95% CI: 63.4-95.4) for early stage versus 75.9% (95% CI: 55.2-89.2) for locally advanced stages, respectively (P=0.18). CONCLUSION: Large cohort data are warranted to guide the optimal management of GCC. From this retrospective analysis, a multimodal approach yielded to good disease control in early stages tumors. Given the high-risk of distant failure, consideration should be given to adjuvant chemotherapy in locally advanced disease.

Adenosquamous carcinoma: An aggressive histologic sub-type of colon cancer with poor prognosis.

BACKGROUND: Studies have reported worse overall survival (OS) for adenosquamous carcinoma (ASC) compared to adenocarcinoma (AC) of the colon, but none have analyzed a national dataset for over 30 years. METHODS: The National Cancer Database was queried from 2004 to 2016 for patients with ASC and AC of the colon. Kaplan-Meier survival analysis was performed to assess OS. Descriptive variables were evaluated using independent T-test and Chi-square analyses. RESULTS: 332 ASC patients were compared to 496,950 AC patients. AC patients were older than ASC patients (68.6 vs. 64.4 years); p < 0.001. Most ASC cancers presented with stage IV (41.3%) and poorly-differentiated disease (57.5%) compared to AC (22.4% and 17.7%). OS of the ASC cohort was 13.9 months. Median OS for stage IV AC versus stage IV ASC was significantly better (14.1 vs. 8.0 months); p < 0.0001. CONCLUSION: This is the largest national database study to compare ASC with AC. Our findings confirm that unlike AC, ASC most frequently presents late stage, as poorly-differentiated lesions, and have worse OS.

Clinical and Histological Basis of Adenosquamous Carcinoma of the Pancreas: A 30-year Experience.

BACKGROUND: Adenosquamous carcinoma (ASC) of the pancreas is a rare form of malignancy with a poor prognosis. We herein report our case series with review of the contemporary literature. METHODS: With institutional review board approval, we identified 23 patients with pancreatic ASC. RESULTS: ASC was more common in women (61%), with a median age of 73 y at presentation. The tumor was in the head of the pancreas in 65% of cases. Six cases (26%) had resectable disease, three (13%) were borderline resectable, and eight (34.7%) were locally advanced or metastatic. First-line treatment included pancreatic resection in eight cases (34.8%), concurrent neoadjuvant chemoradiation in three (13%), and neoadjuvant chemotherapy in two (8.7%). Most resected tumors had pathological T3 stage (80%). Pathological nodal disease was demonstrated in 60%, and margins were positive in three cases. Complete pathological response was not observed, although fibrosis presented in only one case (10%). Eventually, twenty patients developed metastatic disease. Overall survival is 11.5 [95% confidence interval 6, 14.5] months. CONCLUSIONS: ASC demonstrates a more aggressive malignant phenotype and carries a worse prognosis. Oncological resection is the mainstay of treatment. Neoadjuvant chemoradiation is an emerging approach in the management of ASC that has been extrapolated from the adenocarcinoma neoadjuvant trials.

The importance of multimodal therapy in the management of nonmetastatic adenosquamous carcinoma of the pancreas: Analysis of treatment sequence and strategy.

BACKGROUND: Adenosquamous carcinoma of the pancreas has historically poor survival. We analyzed survival outcomes stratified by treatment regimen and sequence using an administrative dataset. METHODS: Adult patients with nonmetastatic adenosquamous carcinoma of the pancreas were identified using the National Cancer Database (2010-2016). Multivariable analyses were used to determine factors associated with receipt of neoadjuvant or adjuvant chemotherapy. Overall survival was estimated by Kaplan-Meier analysis and a multivariable Cox model was used to evaluate factors associated with survival. RESULTS: A total of 838 patients with adenosquamous carcinoma of the pancreas were included in the analysis. The median age was 69 years and 64.7% of patients underwent pancreatectomy. Among patients who underwent pancreatectomy, 60.5% received adjuvant chemotherapy, 14.8% received neoadjuvant chemotherapy, and 24.7% underwent surgery alone. Older age and increasing comorbidity index were associated with a reduced likelihood of receiving neoadjuvant or adjuvant chemotherapy. Median survival of patients who received chemotherapy alone was similar compared with patients who underwent pancreatectomy alone (9.2 vs 7.2 months, P = .504). Survival was improved if patients received both chemotherapy and pancreatectomy (neoadjuvant = 19.6 months, hazard ratio = 0.58; adjuvant = 19.4 months, hazard ratio = 0.64) compared with pancreatectomy alone. CONCLUSION: Patients with adenosquamous carcinoma of the pancreas who do not receive multimodal therapy have poor survival. The sequence of chemotherapy and pancreatectomy is not associated with survival, but 25% of patients who undergo surgery do not receive chemotherapy. Given that there is no difference in median survival between patients who undergo pancreatectomy alone or receive chemotherapy alone, our data question whether neoadjuvant chemotherapy should be considered in patients with potentially resectable adenosquamous carcinoma of the pancreas.

Clinical Efficacy and Safety of Apatinib for the Treatment of Patients with Metastatic, Recurrent Cervical Cancer after Failure of Radiotherapy and First-Line Chemotherapy: A Prospective Study.

PURPOSE: As a small-molecule tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2), apatinib has shown a survival benefit in multiple solid tumors. This study aims to evaluate the efficacy and safety of apatinib in patients with metastatic, recurrent cervical cancer after failure of radiotherapy and first-line chemotherapy. METHODS: A total of 42 patients between June 2018 and March 2019 were involved in this study. All patients orally received apatinib once daily in a 4-week cycle until disease progression or adverse events that prohibit further therapy. The primary endpoint was progression-free survival (PFS), the secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), health-related quality of life (HRQoL) and adverse events. RESULTS: During a median follow-up of 13 months, 8 patients achieved a partial response and 24 cases achieved stable disease. None of them reported a complete response. The ORR and DCR were 19.0 and 76.2%, respectively. The median PFS was 6.0 months (95% CI 4.9-7.1), and the median OS was 12.0 months (95% CI 10.1-13.9). The global health score/HRQoL improved significantly following 3-cycle treatment (50.4 ± 12.5 vs. 60.1 ± 11.8; p < 0.01). The most frequent grade 3-4 adverse events were hand-foot syndrome, hypertension and fatigue. CONCLUSION: Apatinib should be an effective and tolerable treatment option for patients with metastatic, recurrent cervical cancer after failure of radiotherapy and first-line chemotherapy.

Increased proportion of the squamous cell carcinoma component is associated with worse survival in resected gastric adenosquamous carcinoma: A STROBE compliant cohort study.

For the diagnosis of gastric adenosquamous carcinoma (ASC), discrepancies regarding a rational diagnostic proportion of the squamous cell carcinoma (SCC) component exist among different organizations. Our study aimed to evaluate the impact of the SCC component on the survival of gastric cancer patients and identify the optimal cutoff value for the SCC component necessary for diagnosing gastric ASC.Cases of gastric cancer with an SCC component were obtained from our center and from case reports and series extracted from Medline. Univariate and multivariate analyses were conducted to compare the overall survival between groups and examine the prognostic value of various clinical parameters.We identified 45 qualified cases in published literature and 13 in our center. Forty-two of them were males and 16 females (M: F = 2.6:1). Thirty of them were Asian patients and the rest were mainly from the United States and Europe. The mean age was 61.1 years (median 64 years, range 32-84 years). The average tumor size was 6.9 cm (median 6.0 cm, range 2.0-16.0 cm). The most common location of the cancer was the lower third (39.7%). Although a statistical difference was not achieved, the Kaplan-Meier curve demonstrated that as the proportion of the SCC component in the primary lesion increased, the patients' survival risk increased (P = .489), and the presence of the SCC component in metastatic lymph nodes also increased the risk of survival (P = .259); both of these findings indicated a negative impact of the SCC component on survival. Furthermore, we identified the optimal cutoff for the SCC component as 35% (χ = 6.544, P = .011), which was subsequently validated in a Cox regression model as an independent prognostic factor (P = .026).An increased proportion of the SCC component is associated with worse survival in gastric cancer patients with an SCC component. The optimal cutoff for the proportion of the SCC component necessary for the diagnosis of gastric ASC is 35%.

Tumor Location and Survival Outcomes in Lung Adenosquamous Carcinoma: A Propensity Score Matched Analysis.

BACKGROUND There is little information in the literature available on lung adenosquamous carcinoma (LASC). The association between tumor location and survival outcomes in LASC is poorly understood. Our study was designed to probe the effect of tumor location on survival outcomes of LASC. MATERIAL AND METHODS Patients with LASC between 2004 and 2015 were identified using the Surveillance, Epidemiology and End Results (SEER) databases. The patients were divided into 2 groups, a main bronchus group and a peripheral group, according to their primary sites. The Propensity Score Matching (PSM) method was used to reduce possible bias between groups. The primary endpoints were overall survival (OS) and cancer-specific survival (CSS). RESULTS A total of 3176 patients, afflicted with LASC between 2004 and 2015, were extracted from the SEER databases. Of these, 212 patients were found to be eligible for analysis after a propensity 1: 1 nearest neighbor matched analysis. After PSM, multivariate Cox regression analysis showed that primary site, American Joint Committee on Cancer (AJCC) stage, T stage and surgery were independent predictors of LASC in both OS and CSS. Kaplan-Meier survival analysis showed that patients with LASC located in a peripheral site had better survival outcomes than those with LASC located in the main bronchus. In subgroup analysis, the advantages of tumor located in a peripheral site were more pronounced in female patients and AJCC stage I patients. CONCLUSIONS Tumor location may have an impact on the survival outcomes of patients with LASC. Patients with LASC located in a peripheral site had better survival outcomes than patients with LASC located in the main bronchus, particularly in female patients and AJCC stage I patients.

Comparison of adenocarcinoma and adenosquamous carcinoma prognoses in Chinese patients with FIGO stage IB-IIA cervical cancer following radical surgery.

BACKGROUND: To compare adenocarcinoma (AC) and adenosquamous carcinoma (ASC) prognoses in patients with FIGO stage IB-IIA cervical cancer who underwent radical hysterectomy. METHODS: We performed a retrospective analysis of 240 patients with AC and 130 patients with ASC. Kaplan-Meier curves, Cox regression models, and log-rank tests were used for statistical analysis. RESULTS: Patients with ASC had higher frequencies of lymphovascular space invasion (LVSI) and serum squamous cell carcinoma antigen (SCC-Ag) > 5 ng/ml (p = 0.049 and p = 0.013, respectively); moreover, they were much older (P = 0.029) than patients with AC. There were no clinically significant differences in overall survival (OS) between the groups. When stratified into three risk groups based on clinicopathological features, survival outcomes did not differ between patients with AC and those with ASC in any risk group. Multivariate analysis showed that lymph node metastasis (LNM) was an independent risk factor for recurrence-free survival (RFS) and OS in patients with AC and in patients with ASC. Carcinoembryonic antigen (CEA) > 5 ng/ml and SCC-Ag > 5 ng/ml were independent predictors of RFS and OS in patients with AC. In addition, among those stratified as intermediate-risk, patients with ASC who received concurrent chemoradiotherapy (CCRT) had significantly better RFS and OS (P = 0.036 and P = 0.047, respectively). CONCLUSIONS: We did not find evidence to suggest that AC and ASC subtypes of cervical cancer were associated with different survival outcomes. CCRT is beneficial for survival in intermediate-risk patients with ASC, but not in those with AC. Serum tumour markers can assist in evaluating prognosis and in providing additional information for patient-tailored therapy for cervical AC.

Adeno-squamous and squamous cell carcinoma of the gallbladder: The importance of histology in surgical management.

BACKGROUND: Although gallbladder adenocarcinoma (AC) is potentially curable with resection, outcomes of squamous histologies are poorly described. METHODS: We retrospectively analyzed all gallbladder cancers which underwent resection-for-cure in our health system from 2007 to 2017. We compared outcomes of AC to adeno-squamous (ASC)/squamous (SC) histologies. RESULTS: 91 patients met criteria; 76 AC, 15 ASC/SC. Compared to AC, ASC/SC tumors were larger (58 vs. 28 mm), with more frequent liver invasion (73% vs. 37%), pN+ (60% vs. 32%), higher stage (III/IV 73% vs. 52%), and displayed more LVI (60% vs. 36%), p < 0.05. For stage III/IV disease, provided R0 was achieved, survival was durable and similar for ASC/SC and AC (OS median 28mo ASC/SC vs. 25mo AC, p = 0.132; PFS median 21mo ASC/SC vs. 13mo AC, p = 0.206). Pure SC had considerably poorer median OS (<5mo) than ASC (23mo) and AC (28mo). DISCUSSION: Squamous variants of gallbladder cancer confer aggressive and advanced disease and often require more radical resections to achieve R0. Durable survival is possible in ASC provided R0 is achieved. Pure SC has dismal survival even with R0 resection.

Adenocarcinomatous-predominant subtype associated with a better prognosis in adenosquamous lung carcinoma.

BACKGROUND: According to the proportion of glandular and squamous pathological components, adenosquamous carcinoma (ASC) could be divided into adenocarcinoma (AC) and squamous cell carcinoma (SCC) predominant subtypes. Due to its rarity, no study investigating the impact of different subtypes on the clinical features, radiologic findings and prognosis characteristics of ASC has been reported. METHODS: Sixty eight patients who underwent surgical resection for lung adenosquamous carcinoma in our institute between January 2006 and March 2017 were retrospectively reviewed. Data regarding the clinical features, radiologic findings and prognosis characteristics were collected. RESULTS: Thirty nine patients of the study cohort were with AC-predominant ASC and 29 with SCC-predominant ASC. There was no significant difference between the two subgroups in age, gender, smoking history, serum carcinoembryonic antigen (CEA) level and T,N classification. Air bronchogram was found more frequently in AC-predominant ASC than in SCC-predominant ASC (P = 0.046). Multivariate analysis identified pathological subtype (P = 0.022) and CT findings of peripheral location (P = 0.009) to be independent prognostic factors. CONCLUSIONS: AC-predominant ASC were more commonly presented with air bronchogram, and were with a better prognosis than SCC-predominant ASC.