Complete pathologic response to neoadjuvant icotinib in stage IIIA EGFR-mutant lung adenosquamous carcinoma: A case report.

RATIONALE: Radical surgery offers the best chance of cure, it is critical to expand surgery opportunities for patients with early-stage lung cancer to prolong overall survival. However, evidence is still limited regarding the application of neoadjuvant therapy with EGFR-tyrosine kinase. PATIENT: The patient reported here was a 53-year-old woman with right lower lung adenosquamous carcinoma. DIAGNOSES: The lung cancer was staged as T3N1M0. Tumor genotype disclosed EGFR Exon19 c.2235-2249de p.E746-A750del. INTERVENTION: After neoadjuvant treatment with icotinib, she underwent thoracotomy and achieved pathological complete response. OUTCOMES: She is currently receiving adjuvant icotinib therapy without recurrence or metastasis during 18-month follow-up. LESSONS: Our case indicated that the feasibility of neoadjuvant icotinib in EGFR-mutant lung adenosquamous carcinoma.

Adenosquamous carcinoma of the gallbladder simultaneously producing granulocyte-colony-stimulating factor and parathyroid hormone-related protein.

We report a rare case of adenosquamous carcinoma of the gallbladder which simultaneously produces granulocyte-colony-stimulating factor (G-CSF) and parathyroid hormone-related protein (PTHrP), confirmed serologically and histologically. A 71-year-old man was examined for a gallbladder tumor with multiple lymph nodes and liver metastases. Histopathological evaluation by endoscopic ultrasound fine-needle aspiration revealed adenosquamous carcinoma of the gallbladder. Laboratory data showed markedly elevated white blood cell (WBC) count of 34,700 µL and corrected serum calcium level of 14.9 mg/dL. Serum G-CSF (191 pg/mL) and PTHrP (23.1 pmol/L) levels were high. Zoledronic acid and calcitonin were administered to treat hypercalcemia, which normalized serum calcium levels. Gemcitabine-cisplatin chemotherapy was started for cStage IVB gallbladder cancer. After chemotherapy initiation, WBCs showed a rapid downward trend; however, the patient suddenly developed acute respiratory distress syndrome; thus, chemotherapy was discontinued. Subsequently, WBC count increased again, and the patient's overall condition deteriorated. The patient died on day 27. Immunohistochemistry using autopsy specimens demonstrated patchy staining for G-CSF in the squamous cell carcinoma portion and diffuse and weak positive staining for PTHrP in the squamous cell carcinoma and poorly differentiated adenocarcinoma portions of the tumor, suggesting simultaneous G-CSF and PTHrP production by the tumor. This is the first report of a patient with gallbladder cancer with serological and histological evidence for G-CSF and PTHrP production.

A patient with a lung adenosquamous carcinoma harboring a de novo T790M mutation and huge nonbacterial vegetative growths successfully treated with osimertinib: A case report.

Nonbacterial thrombotic endocarditis (NBTE) is a rare condition; sterile vegetations attach to heart valves. NBTE is typically found in patients with malignancies or autoimmune disorders. Although surgical interventions are sometimes performed, the appropriate indication and timing are still unclear. Here, we describe a 72-year-old woman diagnosed with adenosquamous carcinoma of the lung. She was initially diagnosed as pT2aN0M0 and underwent RUL lobectomy. After nine months, lung cancer recurred, and she underwent treatment with cytotoxic chemotherapy. However, images showed progression after only one month. Rebiopsy revealed she had comutation of de novo EGFR L858R and T790M. Treatment was changed to gefitinib. After one month, she experienced loss of consciousness. Brain magnetic resonance imaging (MRI) showed multiple lesions resembling infarctions or metastases. Chest computed tomography (CT) revealed progression. Osimertinib was prescribed and she underwent echocardiography to rule out the possibility of a cardiogenic embolism. Surprisingly, severe mitral regurgitation and a massive vegetation on the mitral valve were found. Cardiologists recommended surgery due to the severity of the embolic event and valve dysfunction, but it was decided to continue antibiotics, osimertinib, and anticoagulants instead of surgery due to the patient's poor general condition and the possibility of NBTE. Six weeks later, the patient's condition markedly improved and echocardiography revealed a marked reduction in vegetation size. Clinicians should be aware that targeted therapy can be effective in treating severe cancer complications, such as NBTE, as evidenced by the successful treatment of lung cancer with osimertinib. This option should be considered, particularly for elderly lung cancer patients, before resorting to surgery as a first-line treatment for NBTE.

Partial response in non-resectable adenosquamous carcinoma of the pancreas with high tumour mutation burden treated with gemcitabine, nab-paclitaxel and pembrolizumab.

A previously healthy man in his 60s was diagnosed with a rare histological subtype of pancreatic cancer, adenosquamous carcinoma. After somatic mutation profiling, it was found that the tumour had microsatellite instability status high and a high tumour mutational burden. The patient was started on combination therapy with gemcitabine, nab-paclitaxel and pembrolizumab. Tumour size and biomarkers showed a dramatic response eventually leading to the patient being transitioned to maintenance therapy with pembrolizumab. The patient has demonstrated continued response since the start of the treatment. This is the first report in the literature showing a sustained response in this type of neoplasm that was treated with a checkpoint inhibitor, and thus adds to the evidence supporting universal somatic testing in all pancreatic cancers for a tailored approach to therapy.

[A case of pancreatic adenosquamous carcinoma successfully treated by chemoradiotherapy].

Pancreatic adenosquamous carcinoma is a rare primary pancreas malignant tumor with very poor prognosis, for which there is no standard treatment. The case was of a 71-year-old woman who was admitted to the hospital with jaundice. A pancreatic head tumor was found, and pancreatic adenosquamous carcinoma was diagnosed in EUS-FNA. Despite confirmed distant metastasis, a multidisciplinary treatment centered on chemoradiotherapy gave her a 28-month prognosis.

Chemotherapy in advanced pancreatic adenosquamous carcinoma: A retrospective multicenter AGEO study.

Pancreatic adenosquamous carcinoma (PASC) account for <5% of pancreatic malignancies. The efficacy of modern chemotherapy regimens in patients with advanced PASC is unknown. Patients with advanced PASC from 2008 to 2021 were consecutively included in this retrospective multicenter study. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method. Ninety-four PASC from 16 French centers were included (median age, 67.3 years; males, 56.4%; metastatic disease, 85.1%). The first-line treatment was chemotherapy for 79 patients (84.0%) (37 FOLFIRINOX (FX), 7 Gemcitabine-nab paclitaxel (GN) and 35 for all other regimen) or best supportive care (BSC) alone for 15 patients (16.0%). No significant difference was observed between FX and GN in terms of PFS (P = .67) or OS (P = .5). Modern regimens pooled together (FX and GN) as compared to all others chemotherapy regimens showed an improvement of overall response rate (39.5% and 9.7%, P = .002), PFS (median, 7.8 vs 4.7 months, P = .02) and OS (median, 12.7 vs 9.2 months, P = .35). This large study evaluating first-line treatment regimens in advanced PASC suggests that modern regimens as FX or GN may be preferable to all other chemotherapy regimens. These results deserve confirmation in prospective studies.

Efficacy of chemotherapy for patients with metastatic or recurrent pancreatic adenosquamous carcinoma: A multicenter retrospective analysis.

BACKGROUND/OBJECTIVES: Pancreatic adenosquamous carcinoma (PASC) is a rare variant of pancreatic ductal adenocarcinoma (PDAC). The usual treatment for metastatic or recurrent PASC is systemic chemotherapy in accordance with the PDAC treatment strategy. This study aimed to investigate the efficacy of chemotherapy, especially the benefit of recent combination therapies, in patients with metastatic or recurrent PASC. METHODS: We conducted a multicenter retrospective analysis of 116 patients with metastatic or recurrent PASC treated with first-line chemotherapy between April 2001 and December 2017 at 24 Japanese institutions. RESULTS: Combination chemotherapies included gemcitabine + nab-paclitaxel (GnP, n = 28), fluorouracil/leucovorin + irinotecan + oxaliplatin (FFX, n = 10), gemcitabine + S-1 (GS, n = 10), and others (n = 9). Monotherapies included gemcitabine (n = 51) and S-1 (n = 8). The median overall survival (OS) was 6.5, 7.3, and 4.3 months for the whole cohort, the combination therapy group, and the monotherapy group, respectively. Multivariate analysis indicated that combination therapy showed a better trend in OS than monotherapy (hazard ratio = 0.68; 95% confidence interval, 0.38-1.20). GnP or FFX were selected in 58.7% of patients after FFX was approved in Japan, and revealed a median OS, median progression-free survival, and objective response rate of 7.3 months, 2.8 months, and 26.9% in GnP and 7.2 months, 2.3 months, and 20.0% in FFX respectively. CONCLUSIONS: This study suggests that combination therapy may be more effective than monotherapy. GnP and FFX showed similar and clinically meaningful efficacy for patients with metastatic or recurrent PASC.

Neoadjuvant ceritinib treatment in ALK-rearranged locally advanced adenosquamous carcinoma: A case report.

Here, we first report a case of neoadjuvant ceritinib for locally advanced lung adenosquamous carcinoma. In this study, a locally advanced adenosquamous carcinoma (ASC) patient with EML4-ALK fusion who achieved a partial response with neoadjuvant ceritinib treatment after a cycle of neoadjuvant chemotherapy did not show significant efficacy. A complete surgical resection was performed with mild adhesions and a small amount of bleeding intraoperatively. The EML4-ALK fusion was detected by targeted next-generation sequencing (NGS) in both pretreatment biopsy and the postoperative tissue specimens with a dramatic decrease in the allele frequency (26.2% [pre]-2.3% [post]). Pathological examination of the postoperative specimens indicated a diagnosis of ASC but the proportions of adenocarcinoma and squamous cell carcinoma cells in the primary lung tumor and metastatic lymph node site were different, suggesting the various responses to ceritinib. Thus, with the case presented here, we provide the clinical evidence for ALK-positive locally advanced ASC patients benefiting from neoadjuvant ceritinib treatment with a tolerable safety profile, whereas further cohort studies of the efficacy and safety of neoadjuvant ceritinib in such patients are needed.

A phase II trial of the super-enhancer inhibitor Minnelide™ in advanced refractory adenosquamous carcinoma of the pancreas.

Adenosquamous carcinoma of the pancreas (ASCP) is a very rare and highly aggressive variant of pancreatic ductal adenocarcinoma, accounting for 0.5-4% of all pancreatic cancer cases in the USA. Current data indicate that epigenetic changes and MYC overexpression lead to squamous transdifferentiation of pancreatic tumor cells and development of ASCP. Minnelide™, an oral anti-super-enhancer drug that inhibits MYC expression in preclinical models of ASCP, has demonstrated safety in a phase I study. We describe the design for a phase II, open-label, single-arm trial of Minnelide in patients with advanced refractory ASCP.

Adenosquamous carcinoma of the pancreas (ASCP) is a rare and highly aggressive variant of pancreatic cancer, with limited treatment options. Changes in activation of DNA elements called super-enhancers drive the growth of ASCP. Minnelide™ is an oral drug that blocks the super-enhancer network and is safe to give to patients with advanced cancer. This trial is designed to determine whether Minnelide can shrink tumors in patients with ASCP who have already received at least one previous treatment for their cancer.  Clinical Trial Registration: NCT04896073 (ClinicalTrials.gov).

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.).

Cost-effectiveness analysis of pembrolizumab for treatment of US patients with persistent, recurrent, or metastatic cervical cancer.

OBJECTIVE: The effectiveness of pembrolizumab for persistent, recurrent, or metastatic cervical cancer has been demonstrated. We aimed to evaluate its cost-effectiveness from the United States (US) healthcare payers perspective. METHODS: A partitioned survival model over a 30-year lifetime horizon was developed to compare the cost and effectiveness of pembrolizumab versus placebo based on clinical data from the KEYNOTE-826 phase 3 randomized trial. Costs and health state utilities were obtained from literature and publicly available databases. The incremental cost-effectiveness ratio (ICER) was measured. One-way and probabilistic sensitivity analyses were conducted. RESULTS: For the Intention-to-Treat patients, pembrolizumab was associated with an additional 0.74 quality-adjusted life-year (QALY) at an additional cost of $182,271 when compared with placebo. The ICER was $247,663/QALY. For patients with a programmed death-ligand 1 combined positive score ≥ 1 and 10, the ICER was $253,322/QALY and $214,212/QALY, respectively. One-way sensitivity analyses showed that pembrolizumab had the greatest impact on the ICER. Probabilistic sensitivity analyses showed that the probability of pembrolizumab being cost-effective was zero at the current willingness-to-pay threshold of $150,000/QALY. The price of pembrolizumab had to reduce at least to $28.336 (55.8% of the current price) for it to be cost-effective in a 50% of chance. CONCLUSION: The addition of pembrolizumab to chemotherapy is costly and might not be cost-effective for persistent, recurrent, or metastatic cervical cancer at the current price in the US.

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.

[A Case of Resected Pancreatic Adenosquamous Carcinoma with Early Hepatic Metastatic Recurrence].

A 73-year-old man was presented with epigastric pain and indicated high CA19-9 levels, and computed tomography detected a tumor in the uncinate process of the pancreas infiltrated duodenum and superior mesenteric artery. The patient was diagnosed with borderline resectable pancreatic carcinoma and received neoadjuvant chemotherapy with gemcitabine and S-1. During neoadjuvant chemotherapy, the patient also received radiotherapy to control duodenal bleeding. After neoadjuvant chemotherapy, stable disease(SD)was proven on the Response Evaluation Criteria in Solid Tumors(RECIST), and subtotal stomach-preserving pancreaticoduodenectomy was performed. The pathological findings showed pancreatic adenosquamous carcinoma. After 7 days postoperatively, hepatic metastasis was detected, and after 78 days postoperatively, the patient died.

[A Patient with Gastric Adenosquamous Cell Carcinoma].

A 73-year-old female was referred from a local clinic with abdominal pain. A diagnosis of gastric cancer(cT3, cN0, M0, cStage ⅡB)and acute cholecystitis was made. Distal gastrectomy, D2, and cholecystectomy were performed. Postoperative pathological examination led to a diagnosis of adenosquamous cell carcinoma(pT3, pN2, M0, pStage ⅢA). SOX therapy was administered as postoperative adjuvant chemotherapy. However, multiple liver metastases were detected. XP and DTX therapies were administered; however, there was a reduction in performance status. The patient died 10 months after surgery. Gastric adenosquamous cell carcinoma is classified as a specific type according to the Japanese Classification of Gastric Carcinoma(15th edition). This carcinoma accounts for 0.3 to 0.5% of patients undergoing gastric cancer surgery and is relatively rare. Its malignancy level is higher than that of gastric adenocarcinoma, and its prognosis is poorer.

Unresectable primary hepatic adenosquamous carcinoma successfully treated with systemic and transcatheter hepatic arterial injection chemotherapies followed by conversion surgery: a case report and literature review.

BACKGROUND: Primary hepatic adenosquamous carcinoma (ASC) is a type of tumor that has the features of both adenocarcinoma and squamous cell carcinoma (SCC). The prognosis for patients with ASC is poor, as the chemotherapy has been ineffective so far. CASE PRESENTATION: Here, we report a case of a 62-year-old male patient who presented with high fever. The tumor marker levels were high, and abdominal dynamic computed tomography showed a liver tumor and distant lymph node metastases. Upon further investigation, needle biopsy of the liver tumor showed a primary hepatic SCC. Because the SCC was unresectable, the patient was treated with tegafur/gimeracil/oteracil (S-1) and transcatheter hepatic arterial injection (TAI) of cisplatin. After chemotherapy, a surgical resection performed on the remaining liver tumor, made the patient cancer-free. After the operation, the liver tumor was confirmed as primary hepatic ASC. Subsequently, the patient was administered postoperative adjuvant chemotherapy, which prevented its recurrence. CONCLUSIONS: Due to the lack of an effective treatment for primary hepatic ASC, its prognosis is poor. Here, we suggest that a chemotherapy combination of 5-fluorouracil (S-1) and cisplatin along with conversion surgery might be an effective way for treating primary hepatic ASC. Our experience from this case shall be valuable to clinicians around the world involved in the treatment of primary hepatic ASC.

Advanced primary adenosquamous carcinoma of the liver with a small cell carcinoma component: an autopsy case report.

Primary adenosquamous carcinoma (ASC) of the liver is a rare subtype of cholangiocarcinoma that comprises both adenocarcinoma and squamous cell carcinoma components. We report a 48-year-old woman with advanced primary ASC and small cell carcinoma of the liver who had extrahepatic metastasis and received multiple chemotherapy regimens. After first presenting with upper abdominal pain, imaging revealed a 10.2 × 9.5 cm mass in the right lobe of the liver with lymph node and lung metastases. A liver tumor biopsy revealed adenocarcinoma and squamous cell carcinoma components, leading to a diagnosis of advanced primary ASC of the liver. The tumor shrank with gemcitabine/cisplatin therapy; however, neuron-specific enolase (NSE) and CYFRA levels were increased and the tumor grew. Next, hepatic arterial infusion chemotherapy using 5-fluorouracil and cisplatin decreased NSE and CYFRA levels and suppressed tumor growth. However, due to tumor growth, she died 14 months post-initial diagnosis. Post-autopsy pathology revealed a mixture of CD56- and synaptophysin-positive small cell carcinoma component in addition to ASC. We report a rare advanced primary ASC with small cell carcinoma of the liver diagnosed at autopsy.

[Erlotinib plus Bevacizumab Therapy for Postoperative Recurrence of Adenosquamous Cell Carcinoma Harboring EGFR Mutation-A Case Report].

A 59-year-old man clinically diagnosed with primary lung cancer underwent left lower lobectomy and lymph node dissection( ND2a-2). The postoperative pathological stage was ⅠB(pT2aN0M0), and the lesion was positive for epidermal growth factor receptor(EGFR)exon 21 L858R mutation. Thirty months after surgery, the patient developed pleural dissemination and effusion in the left pleural cavity. Carboplatin(AUC=6, day 1, every 3 weeks)and nab-paclitaxel(100 mg/m2, day 1 and day 8, every 3 weeks)were administered as first-line therapy. Progressive disease was evident 10 months after 4 courses of first-line therapy. Pembrolizumab(200 mg, day 1, every 3 weeks)was then administered as second-line therapy. After 7 months(9 courses of therapy), the lung cancer had metastasized to the left third intercostal muscle, and the pleural nodules regrew. The former lesion was treated with radiotherapy owing to the development of pain in the chest. Erlotinib (150 mg once daily)and bevacizumab(15 mg/kg, day 1, every 3 weeks)were initiated as third-line therapy, resulting in complete response at 14 months(67 months after surgery, 37 months after postoperative recurrence). The prognosis of patients with EGFR-positive pulmonary adenosquamous carcinoma and undergoing treatment with EGFR-tyrosine kinase inhibitors(TKI)is reportedly poor. Herein, we report a rare case of adenosquamous carcinoma with EGFR mutation presenting complete response following treatment with EGFR-TKI.

A case report of right upper lung adenosquamous carcinoma resection following neoadjuvant targeted therapy.

The patient was a middle-aged male smoker who had space-occupying lesions in the right upper lung, Positron emission tomography-computed tomography (PET-CT) suggested right upper lung cancer with multiple mediastinal lymph node metastases. Endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-GS-TBLB) performed in the bronchus of the right apical segment confirmed the lesion as squamous cell carcinoma. Neoadjuvant therapy was planned. Because genetic testing revealed the epidermal growth factor receptor (EGFR) L858R mutation, the possibility of adenosquamous carcinoma was considered. The patient was clinically diagnosed with right upper lung squamous cell carcinoma c-T3N2M0, stage IIIB, and PS 1 point. Dacomitinib was selected for the targeted therapy. Eight weeks after the initiation of treatment, efficacy was assessed as a partial response (PR), suggesting a possibility of R0 resection. After sufficient communication with the patient and his family members, on July 1, 2020, thoracoscopic radical resection of the right upper lung cancer was performed under general anesthesia. Postoperative pathology confirmed adenosquamous carcinoma, of which 80% were adenocarcinoma and 20% were squamous cell carcinoma; no tumor thrombus was seen in the interstitial vessels; and the tumor did not invade the visceral pleura. There was no cancerous infiltration in the bronchial stump of the right upper lung. The following were the results for lymph nodes submitted for examination: L2 (0/1), L4 (0/4), L7 (0/3), L8 (0/7), L10 (0/1), L11 (0/2) and L11 (frozen 0/1) showed no cancer metastasis. The postoperative diagnosis was as follows: adenosquamous carcinoma of the right upper lung p-T2N0M0, stage Ib. After surgery, 4 cycles of the GC (gemcitabine + carboplatin) chemotherapy regimen were given, with continued targeted therapy recommended for 2 years. The patient has been followed-up and is in good condition.

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.