Clinical Stage IVB Research Articles

Multidisciplinary team meetings improve survival in patients with esophageal cancer.

Multidisciplinary team meetings (MDTs) are recommended for patients with esophageal cancer. Improved staging, timeliness to surgery and better adherence to guidelines have been attributed to MDTs, but there are few studies published on the MDTs' effect on survival. All patients with esophageal cancer in Sweden between 2006 and 2018 were grouped according to whether they had been discussed at an MDT as part of their clinical pathway. Factors affecting group allocation were explored with multivariable logistic regression, and the impact of MDT on survival was studied with Cox-regression and the Kaplan-Meier estimator. Of 6837 included patients, 1338 patients (20%) were not discussed at an MDT. Advanced age (80-90years; odds ratio [OR] 0.25, 0.16-0.42 (95% confidence interval)) and clinical stage IVb (OR 0.65, 0.43-0.98) decreased the probability of being presented at an MDT, whereas high education level (OR 1.31, 1.02-1.67), being married (OR 1.20, 1.01-1.43), squamous histology (OR 1.50, 1.22-1.84) and later year of diagnosis (OR 1.33, 1.29-1.37 per year) increased the probability of an MDT. In multivariable adjusted analysis, MDT discussion was associated with improved survival (hazard ratios 0.72, 0.66-0.78) and median survival increased from 4.5 to 10.7months. MDTs were associated with improved survival for esophageal cancer patients. Elderly patients with advanced disease and poor socioeconomic status were less likely to be presented at an MDT, but had clear survival-benefits if they were discussed in a multidisciplinary setting.

Successful R0 resection after chemotherapy, including nivolumab, for gastric cancer with liver metastases: three case reports

BackgroundAdvances in chemotherapy have increased clinical experience with conversion surgery for inoperable advanced gastric cancer. This report describes three patients with unresectable gastric cancer accompanied by multiple liver metastases. In all three patients, nivolumab resolved the liver metastases and subsequent conversion surgery achieved a pathological complete response.Case presentationIn Case 1, a 68-year-old man with clinical Stage IVB gastric cancer and multiple liver metastases initiated first-line therapy with SOX plus nivolumab. The patient completed 13 cycles; however, only nivolumab was continued for 3 cycles because of adverse events. Distal gastrectomy and partial hepatic resection were performed because of a significant reduction in the size of the liver metastases as observed on magnetic resonance imaging (MRI). In Case 2, a 72-year-old man with clinical Stage IVB gastric cancer and multiple liver metastases initiated first-line therapy with SOX. Because of the subsequent emergence of new liver metastases, the patient transitioned to ramucirumab plus paclitaxel as second-line therapy. Third-line therapy with nivolumab was initiated because of side effects. MRI revealed necrosis within the liver metastasis, and the patient underwent proximal gastrectomy and partial hepatectomy. In Case 3, a 51-year-old woman with clinical Stage IVB gastric cancer accompanied by multiple metastases of the liver and para-aortic lymph nodes began first-line therapy with SOX plus nivolumab. The patient completed 10 cycles; however, only nivolumab was continued for 5 cycles because of adverse events. Computed tomography showed a significant decrease in the size of the para-aortic lymph nodes, while MRI indicated the presence of a singular liver metastasis. Distal gastrectomy and partial hepatic resection were subsequently performed. In all three cases, MRI revealed the presence of liver metastases; however, pathological examination showed no viable tumor cells.ConclusionsWe herein present three cases in which chemotherapy, including nivolumab, elicited a response in patients with multiple unresectable liver metastases, ultimately culminating in R0 resection through conversion surgery. Although MRI showed liver metastases, pathological analysis revealed no cancer, underscoring the beneficial impact of chemotherapy.

Tislelizumab combined with nab-paclitaxel single-agent chemotherapy plus bevacizumab for patients with EGFR-TKIs-resistant advanced NSCLC with ECOG PS 0-2.

e20138 Background: Treatment options are limited for EGFR-TKIs-resistant advanced NSCLC. A retrospective study from our center showed that ICIs plus platinum-free, single-agent chemotherapy provided progression-free survival, overall response rate benefit, and a low rate of severe AEs in such pts. Meanwhile,there were many NSCLC patients after treatment failure with EGFR-TKIs who ECOG performance status was 2 ,they were excluded from existing prospective studies. This study was designed to further explore the efficacy and safety of Tis plus nab- paclitaxel and Beva foradvancedNSCLCpts with ECOG ps 0-2 failed to EGFR-TKIs. Methods: This is a single-arm, phase II study (NCT04310943). Pts with EGFR mutations who had failed to prior EGFR-TKIs accepted Tis (200mg, d1) ,nab-paclitaxel (100mg/m2, d1,8,15) and Beva (15mg/kg, d1) Q3W for up to 4 cycles, followed by Tis plus Beva (7.5mg/kg) maintenance therapy. Primary endpoints are 6m-PFS% and safety, secondary endpoints include ORR and 1-year OS rate. The planned sample size was 24 with unacceptable control of 25%, an expected value of 55%, a one-sided α of 0.05, and a power of 80%, Simon's two-stage design. Results: The median age was 57 (range: 30-70). Thirteen pts (54.2%) harbored EGFR exon 19del and 9 pts (37.5%) had exon 21 L858R at the initial diagnosis. There were 9 pts (37.5%) with ECOG ps 2 and18 pts (75%) with clinical stage IVB. Twelve pts (50%) had stable brain metastases. Fifteen pts (63.6%) progressed on both 1st/2nd and 3rd EGFR-TKIs. As of Dec30, 2023, The median follow-up time was 22.2 m (95%CI 0-51.1). Among the 21pts in the efficacy analysis set, the median PFS was 6.3 m(95%CI 5.5-7.1), the 6m-PFS % was 61.6%, the 6m-PFS% of pts with ECOG ps 2 was18.1%. The ORR was 61.9%, the median DOR was 4.4 m (95%CI 2.1-6.7), DCR was 100.0%. The median OS was 15.4 (95%CI 10.1-20.7) and 1y-OS% was 59.7%. The safety was manageable: the incidence of ≥grade 3 TRAE was 25%. Conclusions: Tislelizumab combined with nab-paclitaxel plus bevacizumab is effective with a manageable safety profile for EGFR-TKIs resistant NSCLC patients with ECOG ps 0-2. Clinical trial information: NCT04310943 . [Table: see text]

Association between interstitial lung abnormality and mortality in patients with esophageal cancer.

To investigate the relationship between interstitial lung abnormalities (ILAs) and mortality in patients with esophageal cancer and the cause of mortality. This retrospective study investigated patients with esophageal cancer from January 2011 to December 2015. ILAs were visually scored on baseline CT using a 3-point scale (0 = non-ILA, 1 = indeterminate for ILA, and 2 = ILA). ILAs were classified into subcategories of non-subpleural, subpleural non-fibrotic, and subpleural fibrotic. Five-year overall survival (OS) was compared between patients with and without ILAs using the multivariable Cox proportional hazards model. Subgroup analyses were performed based on cancer stage and ILA subcategories. The prevalences of treatment complications and death due to esophageal cancer and pneumonia/respiratory failure were analyzed using Fisher's exact test. A total of 478 patients with esophageal cancer (age, 66.8years ± 8.6 [standard deviation]; 64 women) were evaluated in this study. Among them, 267 patients showed no ILAs, 125 patients were indeterminate for ILAs, and 86 patients showed ILAs. ILAs were a significant factor for shorter OS (hazard ratio [HR] = 1.68, 95% confidence interval [CI] 1.10-2.55, P = 0.016) in the multivariable Cox proportional hazards model adjusting for age, sex, smoking history, clinical stage, and histology. On subgroup analysis using patients with clinical stage IVB, the presence of ILAs was a significant factor (HR = 3.78, 95% CI 1.67-8.54, P = 0.001). Subpleural fibrotic ILAs were significantly associated with shorter OS (HR = 2.22, 95% CI 1.25-3.93, P = 0.006). There was no significant difference in treatment complications. Patients with ILAs showed a higher prevalence of death due to pneumonia/respiratory failure than those without ILAs (non-ILA, 2/95 [2%]; ILA, 5/39 [13%]; P = 0.022). The prevalence of death due to esophageal cancer was similar in patients with and without ILA (non-ILA, 82/95 [86%]; ILA 32/39 [82%]; P = 0.596). ILAs were significantly associated with shorter survival in patients with esophageal cancer.

Esophageal cancer in an adult with congenital esophageal stenosis: a case report

BackgroundCongenital esophageal stenosis (CES) is a rare condition. We encountered a case of esophageal cancer that developed in an adult with persistent CES. Although many studies have investigated the therapeutic outcomes and performed surveillance for symptoms after treatment for CES, few have performed long-term surveillance or reported on the development of esophageal cancer. We report this case because it is extremely rare and has important implications.Case presentationA 45-year-old woman with worsening dysphagia was transferred to our hospital. The patient was diagnosed with CES at 5 years of age and underwent surgery at another hospital. The patient underwent esophageal dilatation for stenosis at 36 years of age. Esophagoscopy performed at our hospital revealed a circumferential ulcerated lesion and stenosis 15–29 cm from the incisors. Histological examination of the biopsy specimen revealed squamous cell carcinoma. Computed tomography (CT) revealed abnormal circumferential wall thickening in parts of the cervical and almost the entire thoracic esophagus. 18F-fluorodeoxyglucose-positron emission tomography-CT revealed increased uptake in the cervical and upper esophagus. No uptake was observed in the muscular layers of the middle or lower esophagus. Based on these findings, the patient was diagnosed with clinical stage IVB cervical and upper esophageal cancer (T3N1M1 [supraclavicular lymph nodes]). The patient underwent a total esophagectomy after neoadjuvant chemotherapy. The esophagus was markedly thickened and tightly adhered to the adjacent organs. Severe fibrosis was observed around the trachea. Marked thickening of the muscular layer was observed throughout the esophagus; histopathological examination revealed that this thickening was due to increased smooth muscle mass. No cartilage, bronchial epithelium, or glands were observed. The carcinoma extended from the cervical to the middle esophagus, oral to the stenotic region. Finally, we diagnosed the patient with esophageal cancer developing on CES of the fibromuscular thickening type.ConclusionsChronic mechanical and chemical irritations are believed to cause cancer of the upper esophagus oral to a persistent CES, suggesting the need for long-term surveillance that focuses on residual stenosis and cancer development in patients with CES.

First-line FOLFOX therapy for advanced esophageal squamous cell carcinoma: Multicenter prospective study in Japan.

280 Background: Cisplatin (CDDP) plus fluoropyrimidine was the standard first-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC). FOLFOX is promising option especially in patients with ESCC intolerant to CDDP but there were limited data on efficacy and safety of FOLFOX. We conducted a multicenter prospective observational study of FOLFOX for Japanese patients with ESCC intolerant to CDDP. Methods: Eligible participants had clinical stage IVB ESCC, with measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status 0–2, intolerant to CDDP, but tolerant to FOLFOX. FOLFOX (oxaliplatin 85 mg/m², leucovorin 200 mg/m², bolus fluorouracil 400 mg/m², and infusional fluorouracil 2400 mg/m²) was administered every 14 days. The primary endpoint was the response rate (RR) by RECIST v1.1 and the null hypothesis of RR was 10%. Based on the assumption of performing a one-sided test with an α of 0.10, 29 patients were needed to ensure the statistical power of 90% assuming RR of 30%. Results: In this study, 31 patients were enrolled from 14 hospitals between Apr. 2021, and Jul. 2022 and 30 patients received FOLFOX. The patient characteristics were: median age, 77 (range 66–89); male/female, 30/1; ECOG PS 0/1/2, 16/12/3; median creatinine clearance, 49.9 ml/min (33.4–80.2); median G8 score, 12 (range 7–17); and median CARG score, 8 (range 6–13). As the data cutoff of Jul 2023, all 30 patients discontinued FOLFOX. The reason for treatment discontinuation was disease progression, 86.7%; adverse events, 13.3%. Median follow-up time (interquartile range: IQR) was 20.2 (IQR 13.7–23.1) months. Median number of cycles administered were 5 (range 1–24). The RR was 22.6% (80%CI 0.13–0.35; p = 0.031) and disease control rate was 42.0%. Median progression-free survival was 3.9 months (95% CI 2.3–6.1). Median overall survival was 13.3 months (95% CI 9.5–not reached). The incidence of grade 3 or higher adverse events was 40% (neutropenia 26.7%, anemia 3.3%, nausea 6.7%, anorexia 6.7%, infection 6.7%, peripheral sensory neuropathy 3.3%). There was no treatment related death. Twenty-three patients (76.7%) received subsequent therapies, such as nivolumab (70%). Conclusions: First-line FOLFOX showed an acceptable safety profile and the prespecified statistical efficacy target was achieved. FOLFOX might be a treatment option for advanced ESCC patients who are intolerant to CDDP. Clinical trial information: UMIN000044485 .

Urine Phthalate Metabolites are Elevated in Patients with Esophageal Squamous Cell Carcinoma and Associated with Advanced Cancer Stage and Poor Survival.

The aim of this study was to investigate the role of phthalate in patients with esophageal squamous cell carcinoma (ESCC). A total of 116 ESCC patients and 58 controls without any known histories of malignancies were enrolled. All eight urine phthalate metabolites were measured to assess phthalate levels. Clinical and urine phthalate metabolite profiles were compared between subgroups to identify differences, and the effects of phthalates on clinical ESCC outcomes were also examined. The concentrations of some urine phthalate metabolites were higher in the ESCC group than in the control group, including mono-(3-carboxypropyl) phthalate (MCPP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-n-butyl phthalate (MnBP). Higher concentrations of urine phthalate metabolites were associated with clinical T3-T4 status. Patients with higher concentration of mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-2-ethylhexyl phthalate (MEHP), and MEOHP had lower 1-year and 2-year overall survival (OS) rates than those with lower concentrations of these metabolites in our univariate analysis. Multivariate analysis showed that urinary MEHP of ≥3 μg/L and clinical stage IVB were independent prognostic factors for worse OS. The results of our study showed that urine phthalate metabolites are elevated in ESCC patients and associated with advanced tumor stage, and that a high urinary concentration of MEHP is an independent prognostic factor of worse OS.

Treatment strategy for successful conversion surgery in clinical stage IVB gastric cancer

IntroductionRecent advances in chemotherapy have resulted in successful conversion surgery (CS) for clinical stage (cStage) IVB gastric cancer (GC). This study aimed to evaluate the success rate of CS in clinical practice and determine optimal treatment strategies. MethodsTotally, 166 patients with cStage IVB gastric and gastroesophageal junction adenocarcinoma, who underwent chemotherapy at Hyogo Medical University Hospital between January 2017 and June 2022, were included. CS was performed after confirming tumor to be M0 based on imaging and/or staging laparoscopy, except for resectable liver metastases. Preoperative chemotherapy was continued for at least 6 months provided that adverse events were manageable. ResultsOf 125 eligible patients, 23 were treated with CS, achieving a conversion rate of 18.4% and an R0 resection rate of 91.3%. The median duration of preoperative chemotherapy was 8.5 months; the median number of cycles was eight. The highest conversion rate was observed in patients receiving first-line treatment (14.4%), followed by those receiving second and third lines (5.8% and 2.3%, respectively). The median survival time in patients who received CS was significantly longer than that in patients who continued chemotherapy alone (56.7 versus 16 months, respectively, P < 0.0001). There was no significant difference in the 3-year overall survival between the patients who achieved CS after first-line treatment (63.2%, n = 18) and those who achieved CS after second- or third-line treatment (66.7%, n = 5). ConclusionConsistent chemotherapy strategies could lead to successful CS and improved prognosis in a greater number of patients with cStage IVB GC, regardless of line of treatment.

T-cell lymphoma involving the rectum of a dog

A mediastinal mass was diagnosed in a 7-year-4-month-old neutered female mixed breed dog following a 3-week history of lethargy, hyporexia and pyrexia. Bi-cavitary imaging, needle aspirate cytology and flow cytometry confirmed WHO clinical stage IVb, intermediate to large T-cell lymphoma involving the mediastinum, liver and spleen. The dog initially responded to a multidrug chemotherapy protocol but clinical deterioration occurred 3 months later. The dog presented with anorexia, vomiting and diarrhoea, associated with marked faecal tenesmus and haematochezia, initially believed by the primary care practitioner to be related to chemotherapy toxicity. However, rectal examination revealed multiple sessile and pedunculated masses. Further diagnostic imaging, cytology and flow cytometry confirmed progressive disease, including T-cell lymphoma of the rectum. Histology and immunohistochemistry confirmed an infiltrate of intermediate-sized CD3-positive neoplastic cells that expanded the rectal mucosa. Rectal lymphoma is uncommon in dogs and previous cases have been B cell in origin. In this report we describe the clinical presentation and macro- and microscopic findings of a case of canine T-cell lymphoma involving the rectum.

The Relationship Between Poly-ADP-Ribose Polymerase-1 (PARP-1) Expression with Clinicopathological Characteristics of Nasopharyngeal Carcinoma in Bali, Indonesia

Background: According to epidemiological research conducted in Bali, nasopharyngeal carcinoma (NPC) is the most common cancer among males, accounting for 4.9% of total cases reported between 2017 and 2019. NPC is typically detected at stage IV, indicating the presence of distant metastasis by malignant cells. However, research on the role of Poly-ADP-Ribose Polymerase-1 (PARP-1) in this type of cancer is still limited. Therefore, this research aims to investigate the relationship between PARP-1 and the clinicopathological aspects of NPC.Methods: This research employed an analytical observational design with a cross-sectional approach. From January 2018 to July 2022, biopsy tissue samples were collected from NPC patients, strictly following predefined inclusion and exclusion criteria. The clinical data of these patients were extracted from electronic medical records. Subsequently, the collected samples were subjected to immunohistochemical staining for PARP-1. The interpretation of PARP-1 results was conducted using the H-Score method. Data were analyzed using statistical software, specifically SPSS version 25.Results: The results showed that high PARP-1 expression was detected in 18 samples (62.1%), while the low aspect was observed in 11 samples (37.9%). Independent T-test analysis was conducted for sex, age, and clinical stage. No significant difference was found in the mean PARP-1 H-score among groups based on gender, age, and lymph node enlargement, with p-values of 0.68, 0.71, and 0.74, respectively. However, a statistically significant association was found between PARP-1 expression and clinical stage (p=0.02, 95% CI 1.45 – 63.50). Multivariate analysis showed that sex, age, lymph node enlargement, and clinical stage accounted for 22.1% of the variation in PARP-1 expression, with the clinical stage demonstrating a significant correlation (p=0.02). Conclusions: The clinicopathological data of NPC indicate a male-to-female ratio of 3:1. It was discovered that clinical stages IVA and IVB were the most commonly observed stages. Statistically significant differences were found in the mean and proportion of PARP-1 H-scores across different clinical stages. Future reviews need to include other histological subtypes and employ a prospective research design to evaluate the relationship between PARP-1 and NPC.

Oncoguía de cáncer de vulva 2023

Vulvar cancer is a rare neoplasm. Risk factors for the development of vulvar cancer include advanced age, human papillomavirus infection leading to high-grade squamous intraepithelial lesions, smoking, inflammatory conditions affecting the vulva, immunodeficiencies such as human immunodeficiency virus infection, and the presence of well-differentiated vulvar intraepithelial neoplasia (VIN) in patients from 65 to 70 years. VIN may be asymptomatic or present with a mixed variety of symptoms, including itching, discomfort, burning, pain during sexual intercourse, and whitish spots over the vulva. The most common histologic subtype is squamous cell carcinoma. The 5-year survival is 86 % for early clinical stages (CS) I-II, 53 % for locally advanced CS III-IVA, and 19 % for metastatic disease CS IVB. The classic treatment for high-grade VIN is surgical excision and, in the case of multifocal lesions, vulvectomy. Treatment is predominantly surgical in the early stages.

Salvage Surgery for Advanced Lung Adenocarcinoma After Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Treatment

BackgroundNo published studies to date have evaluated the detailed pathologic and genetic features of lung adenocarcinoma after epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy and salvage surgery. We aimed to evaluate the pathologic and genetic changes of tumors in patients with advanced lung adenocarcinoma treated with EGFR TKI therapy and salvage surgery. MethodsThis study retrospectively collected data from 29 advanced lung adenocarcinoma patients who underwent EGFR TKI therapy, followed by salvage operation, between January 2010 and December 2018. All patients had partial response or stable disease without evidence of progressive disease. Next-generation sequencing was used to determine whether acquired resistant mutations in morphologically treatment-sensitive and morphologically treatment-resistant regions of tumor existed. ResultsThere were 3, 22, and 4 patients with clinical stage IIIB, IVA, and IVB, respectively. After a mean TKI treatment duration of 134 days, 27 patients had partial response, 2 had stable disease, and 27.6% of patients were downstaged before salvage surgery. All patients had residual viable tumor cells in their tumor bed; 5 patients (17.2%) had a major pathologic response. Acquired T790M mutations (n = 4), histologic transformations (n = 2), and acquired T790M mutation with histologic transformation (n = 1) were identified in the morphologically treatment-resistant regions of tumors. The 3-year overall survival was 75.9%. ConclusionsThe presence of morphologically treatment-resistant tumor regions with acquired T790M mutations and histologic transformations demonstrate the existence of resistant subclones in TKI-treated tumors before disease progression. Salvage surgery performed in selected patients before disease progression may improve survival by removing TKI-resistant subclones.

Evaluation of anaplastic thyroid carcinoma in the Kurdistan region of Iraq

BackgroundAnaplastic thyroid carcinoma is a rare and lethal disease that accounts for 1–2% of thyroid malignancies. It is an aggressive locoregional disease with a high rate of distant metastasis, a poor prognosis, and a mean survival rate of 3–6 months after diagnosis. This retrospective study aimed to analyse the clinical and pathological features of ATC to assess treatment procedures and its outcome.MethodsWe analysed data from 22 patients diagnosed with ATC from 2018 to 2021, using the Kaplan-Meier method and log-rank test to determine overall survival.ResultsPatients’ median age was 64.3 ± 17.1 years. Females were more affected (male/female ratio: 1:1.7); 14 cases occurred in females (63.6.4%), and eight in males (36.4%). The most common manifestations were neck enlargement (81.8%) and dyspnoea (72.27%), and the tumour size was > 4 cm in 17 (77.3%) patients. The percentage of cases that presented in clinical-stage IVA was 36.4%, with 31.8% presenting in clinical-stage IVB and 31.8% presenting in clinical-stage VIB. Among 22 cases, 14 (63.6%) were operable, and 8 (36.4) were inoperable (p = 0.015). Multimodal therapies were associated with better survival (surgery plus radiotherapy without systemic treatment, P = 0.063). The median overall survival was three months (IC 95%, 0.078–5.922). One-year and two-year survival rates were 9% and 4.5%, respectively.ConclusionATC is a rapidly growing cancer that, fortunately, is rare. Early diagnosis and multimodality treatment may provide a better quality of life and survival time for this group of patients.

440. MULTIDISCIPLINARY TREATMENT CONFERENCE IMPROVES SURVIVAL IN ESOPHAGEAL CANCER

Abstract The advantages of multidisciplinary treatment conferences (MDT) are advocated in staging and treatment of esophageal cancer. Improved timeliness to surgery, adherence to guidelines, increased probability of complete clinical staging and allocation to curative treatment have all been attributed to the introduction of MDTs but there are few studies published in support of MDTs positive effect on outcomes. The aim is to investigate the association between MDT and survival in esophageal cancer. All patients diagnosed with esophageal cancer in the Swedish Registry for Esophageal and Gastric Cancer between 2006-2018 were included in this retrospective cohort study. Patients were grouped according to whether or not they had been discussed at an MDT as part of their staging process. The cohort was followed until death, emigration, or end of follow-up. Factors possibly affecting group allocation was explored with multivariable logistic regression and the impact of MDT on survival was studied with Cox-regression and the Kaplan–Meier method. Of 6607 patients diagnosed with esophageal cancer, 1338 (20%) were not discussed at an MDT. Median survival was 10.7 months with MDT and 4.4 months without MDT. Age above 80, OR 0.29 (0.18-0.47 95%CI), Charlson Comorbidity Index&amp;gt;2, OR 0.79 (0.66-0.96) and clinical stage IVb, OR 0.66 (0.44-0-97) all decreased the probability of being presented at an MDT, whereas squamous cancer, OR 1.45 (1.18-1.77) and later year of diagnosis OR 1.33 (1.30-1.37 per year) increased the probability of an MDT. Adjusted for the well-established prognostic factors above, the MDT was still an independent predictor of survival, HR 0.63 (0.58-0.69 95%CI). The role of the MDT in the staging and treatment of patients with esophageal cancer is, in the present study, clearly associated with improved survival. Older, more comorbid patients with advanced disease are at a disadvantage since they are not consistently discussed in a multidisciplinary setting. Whether the survival benefit is due to the MDT alone or lack of ambition in what appears to be non-curable cases is yet to be determined.

538. A DECADE OF ESOPHAGEAL AND ESOPHAGO-GASTRIC JUNCTION CANCER EPIDEMIOLOGY IN NATIONAL CANCER INSTITUTE MEXICO

Abstract In 2020, the incidence of esophageal cancer was 8th and mortality was 6th in the world. However, it´s not the top 10 in Mexico. Mexico is a developing country and has no national cancer registration. Moreover, Mexico is the 2nd largest obese country in the world, and obesity is one of the leading factors for adenocarcinoma. Therefore, we believe that the actual incidence of esophageal cancer in Mexico is likely to be higher. Retrospective study of patients diagnosed as esophageal and esophago-gastric junction (EGJ) cancer from January 2011 to September 2021. We used the 8th edition (AJCC) to separate esophageal and esophago-gastric junction from gastric cancer and determine the clinical stage. Descriptive statistics were used and Mean Overall Survival (MOS) and Overall Survival (OS) were figured from the date of diagnosis to the date of death or the last follow-up. Kaplan-Meier was used to assess the patients' survival and the differences in subgroups were analyzed by the log-rank with SPSS ver.26. 617 patients were admitted during the period (496 were esophageal and 121 true EGJ). The ratio was men 500 (81%) to women 117 (19%) and the mean age was 60.7±12.3 y.o. (18-90). Main symptoms were solid dysphagia 466 (75.5%) and weight loss 508 (82.3%). The mean BMI was 23.8± 4.6(14.6-42.6). The main histology was intestinal adenocarcinoma 288 (46.7%) and then squamous cell carcinoma 214 (34.7%). Clinical stage IVB 325 (52.7%) and III 213 (34.5%) were the most frequent and 158 (25.6%) cases could not start treatment. The mean following was 11 (0-98) months, MOS was 19.1 (95%CI,16.4-21.9) months and OS was 30.8%. The 5-year SV by stage were I-100%, IIA-37%, IIB-16%, III-15%, IVA-B 6%. This study shows epidemiology from National Cancer Institute in Mexico. Most patients were men in their 60s. The main histology was adenocarcinoma, yet we had many squamous cell carcinoma cases. Although Mexico is the second largest obese country in the world, our patients in the average were not obese. Unfortunately, most patients are diagnosed in advanced stage (IVB) and it might cause the poor prognosis of survival.

A phase II study of osimertinib in combination with platinum plus pemetrexed in patients with EGFR-mutated, advanced non–small cell lung cancer: The OPAL study (NEJ032C/LOGIK1801).

9097 Background: Osimertinib (OSI), a third-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI), is now a standard treatment for previously untreated EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC). In the two randomized phase 3 studies, progression-free survival (PFS) and overall survival were statistically significant and clinically longer with gefitinib and platinum-based chemotherapy compared with gefitinib monotherapy. Based on these data, we have planned this phase 2 study to evaluate the safety and efficacy of OSI combined with platinum-based chemotherapy. Patients and Methods: This multicenter phase 2 study enrolled patients (pts) with clinical stage IIIB, IIIC, IVA, IVB or postoperative recurrent, previously untreated EGFRm NSCLC. Pts received oral OSI 80mg once daily (QD), with either cisplatin 75mg/m2 (arm A) or carboplatin [area under the curve (AUC) = 5, arm B], plus pemetrexed (PEM) 500 mg/ m2 every 3 weeks (Q3W) for four cycles. In both arms, maintenance was OSI 80mg QD with PEM 500 mg/ m2 Q3W until disease progression or discontinuation. The co-primary endpoints were the safety and the objective response rate (ORR), and the secondary endpoints included the complete response rate (CRR), disease control rate (DCR), and PFS. Results: From July 2019 to February 2020, 67 pts (34 pts in Arm A; 33 pts in arm B) were enrolled: median (range) age 67 (26-75) years; 43 (64.2%) female; 46 (68.7%) ECOG PS 0; 66 (98.5%) adenocarcinoma; 31 (46.3%) EGFR exon19 deletion, 35 (52.2) L858R, and 1 (1.5%) both. One pt did not comply with the eligibility criteria and was excluded from the efficacy analysis. At data cut off (August 31, 2021), 27 (40.3%) pts [15 (44.1%) in arm A and 12 (36.4%) in arm B] had discontinued the protocol treatment, including 9 (13.4%) pts [5 (14.7%) in arm A and 4 (12.1%) in arm B] due to the adverse event (AE). The rate of grade (G) ≥ 3 AEs were 91.0% (88.2% in arm A and 93.9% in arm B). For the safety, neutropenia, anemia and thromobocytopenia were numerically higher in arm B and the rates of G ≥ 3 were 29.4%/60.6%, 14.7%/27.3% and 0.0%/42.4% in arm A/B, respectively. G ≥ 3 QTc interval prolonged and G ≥ 2 anorexia were observed in 14.7%/21.2% and 26.5%/24.2%, respectively. For the efficacy, the ORR was 90.9% [95% confidence interval (CI); 84.0-97.8%]. The CRR/DCR were 3.0%/97.0% (95% CI; 0.0-7.2%/92.8%-100.0%), respectively. At a median follow-up time of 21.4 months (range, 18.2-25.7), median PFS was not reached in both A and B, with an estimated 12-/24-months PFS rate of 90.4%/70.0%. Conclusions: OSI combined with platinum-based chemotherapy for previously untreated EGFRm advanced NSCLC showed the excellent efficacy with tolerable toxicity. This combination treatment is highly promising and should be validated in the phase 3 study. Clinical trial information: jRCTs031180226.

Camrelizumab for the treatment of advanced cervical adenocarcinoma: a case report and literature review

Cervical adenocarcinoma belongs to an invasive subtype of cervical carcinoma, presenting poorly prognostic status. Chemotherapy treatment for recurrent cervical carcinoma are thought to be limited and supposed to be noncurative. Because of the poor prognosis of patients with recurrent cervical carcinoma, however, the benefits of second-line chemotherapy have not yet reached a consensus. Immunotherapy is a split-new tactic of overwhelming carcinomas that relies on the instinct of the immune system to recognize and directly kill neoplasm cells. Here, we reported a 55-year-old female patient with clinical stage IVB cervical adenocarcinoma. The patient received four cycles of systematic therapy, with the regimen of docetaxel plus carboplatin in combined with bevacizumab anti-vascular therapy. The progressive disease (PD) was assessed by imaging evaluation and PD was confirmed once more after four cycles of chemotherapy of albumin paclitaxel plus cisplatin. The patient exhibited a good response during the twelve-cycle of immunotherapy of Camrelizumab, whereas PD was observed upon termination of her immunotherapy. This case with the treatment of PD-1 inhibitor Camrelizumab exhibits a good curative effect and tolerable adverse reactions. In addition, some clinical markers and biomarkers expression levels can be served as the predictors of the effect of anti-PD-1 immunotherapy.

Cisplatin and Irinotecan as First-Line Chemotherapy for Previously Untreated Metastatic Thymic Carcinoma: Updated Analysis.

Platinum-based chemotherapy is the de facto standard treatment for metastatic or unresectable thymic carcinoma. The optimal chemotherapy regimen has not yet been determined, including whether this should be combined with a second- or third-generation anti-cancer agent. We retrospectively evaluated the data of patients with metastatic or unresectable thymic carcinoma who were treated with a combination of cisplatin and irinotecan as first-line chemotherapy between 2002 and 2021 (trial registration UMIN000012175). The primary endpoint was response rate according to the RECIST criteria version 1.1. Secondary endpoints were disease control rate, progression-free survival (PFS), overall survival (OS), and toxicity (adverse events). Some patients analyzed in this study were also included in the previous trial, which was terminated early. For this analysis, we included 18 patients with a median age of 56 years and an Eastern Cooperative Oncology Group performance status of 0 or 1. All patients had clinical stage IVa or IVb thymic carcinoma according to the Masaoka-Koga staging system. The response rate was 44% and the disease control rate was 89%. The median PFS was 8.4 months (95% confidence interval (CI): 2.7–11.6 months) and the median OS was 45.6 months (95% CI: 15.7–69.1 months). Grade 3 or worse hematological toxicity was observed in 5 patients and grade 3 or worse non-hematological toxicity was observed in 3 patients. None of the patients developed febrile neutropenia, and no treatment-related deaths occurred. Thus, the combination of cisplatin and irinotecan as first-line chemotherapy for metastatic thymic carcinoma showed efficacy and acceptable toxicity.

Efficacy of Gefitinib and Methorexate in Patients With Advanced Stage and Recurrent Head and Neck Cancer.

Introduction: Gefitinib, a tyrosine kinase inhibitor (TKI), is an epidermal growth factor receptor (EGFR)-blocking drug that is effective in the treatment of lung cancer with EGFR mutations; however, its benefits for head and neck cancers are uncertain. Therefore, this study aims to determine the efficacy of gefitinib and methotrexate in patients with advanced-stage or recurrent head and neck cancer.Methodology: Two hundred patients of age >18 years with advanced clinical stage either IVA or IVB and recurrent cases were included in this study. Patients were randomly allocated to the gefitinib (n=100) or methotrexate (n=100) group. Each patient was evaluated for demographic variables, addictions, comorbidities and history of cancer followed by clinical and radiological evaluation. Treatment response was evaluated with standard Response Evaluation Criteria in Solid Tumors (RECIST). The primary end point of the study was overall response rate (ORR). SPSS version 25 (IBM Corp., Armonk, NY, USA) was used to analyze data.Results: Overall response of therapy was partial 11% vs 8%, stable disease 52% vs 40%, and progressive disease 33% vs 40% in gefitinib and methotrexate groups respectively. Three patients were lost to follow up in the gefitinib group and one patient in the methotrexate group. Only one death was reported in the gefitinib group and four in the methotrexate group. In recurrent cases, six patients treated with gefitinib showed partial response whereas no case of partial response was reported in the methotrexate group (27.3% vs 0%). Similarly, in the methotrexate group significantly higher numbers of progressive and stable diseases were reported for recurrent cases than in the gefitinib group (p=0.045).Discussion: Gefitinib had marginally better results in terms of overall response and safety as compared to methotrexate, specifically in recurrent cases of head and neck cancer. This benefit for recurrent cases and ease of administration, leading to fewer hospital visits in the coronavirus disease 2019 (COVID-19) era, makes gefitinib superior to methotrexate.

Neoadjuvant Chemoradiotherapy Followed by Esophagectomy with Three-Field Lymph Node Dissection for Thoracic Esophageal Squamous Cell Carcinoma Patients with Clinical Stage III and with Supraclavicular Lymph Node Metastasis.

Simple SummaryThis study aimed to clarify the efficacy of neoadjuvant chemoradiotherapy (NACRT) followed by esophagectomy with three-field lymph node (LN) dissection for clinical Stage III patients and for clinical Stage IVB patients with supraclavicular LN metastasis as the only distant metastatic factor. We observed that NACRT followed by esophagectomy with three-field lymph node dissection is feasible and offers the potential for long-term survival of these patients. It is also suggested that supraclavicular LNs should be treated as regional LNs at least in patients with upper and middle thoracic esophageal squamous cell carcinoma (ESCC).Background: Neoadjuvant chemoradiotherapy (NACRT) followed by esophagectomy is now the standard treatment for patients with resectable advanced thoracic esophageal squamous cell carcinoma (ESCC) worldwide. However, the efficacy of NACRT followed by esophagectomy with three-field lymph node dissection for clinical Stage III patients and for clinical Stage IVB patients with supraclavicular LN metastasis has not yet been determined. Methods: Between 2008 and 2018, 94 ESCC patients diagnosed as clinical Stage III and 18 patients diagnosed as clinical Stage IVB with supraclavicular LN metastasis as the only distant metastatic factor were treated with NACRT followed by esophagectomy with extended lymph node dissection at Akita University Hospital. Long-term survival and the patterns of recurrence in these 112 patients were analyzed. Results: The median follow-up period of censored cases was 60 months. The five-year OS and DSS rates among the clinical Stage III patients were 57.6% and 66.6%, respectively. The five-year OS and DSS rates among the clinical Stage IVB patients were 41.3% and 51.6%, respectively. The most frequent recurrence pattern was distant metastasis (69.2%) in the Stage III patients and LN metastasis (75.0%) in the Stage IVB patients. Conclusion: NACRT followed by esophagectomy with three-field LN dissection is feasible and offers the potential for long-term survival of clinical Stage III ESCC patients and even clinical Stage IVB patients with supraclavicular LN metastasis as the only distant metastatic factor. At least in patients with upper and middle thoracic ESCC, treating supraclavicular LNs as regional LNs seems to be appropriate.