Mature tertiary lymphoid structures are key niches of tumour-specific immune responses in pancreatic ductal adenocarcinomas.

OBJECTIVE: To better understand the immune microenvironment of pancreatic ductal adenocarcinomas (PDACs), here we explored the relevance of T and B cell compartmentalisation into tertiary lymphoid structures (TLSs) for the generation of local antitumour immunity. DESIGN: We characterised the functional states and spatial organisation of PDAC-infiltrating T and B cells using single-cell RNA sequencing (scRNA-seq), flow cytometry, multicolour immunofluorescence, gene expression profiling of microdissected TLSs, as well as in vitro assays. In addition, we performed a pan-cancer analysis of tumour-infiltrating T cells using scRNA-seq and sc T cell receptor sequencing datasets from eight cancer types. To evaluate the clinical relevance of our findings, we used PDAC bulk RNA-seq data from The Cancer Genome Atlas and the PRINCE chemoimmunotherapy trial. RESULTS: We found that a subset of PDACs harbours fully developed TLSs where B cells proliferate and differentiate into plasma cells. These mature TLSs also support T cell activity and are enriched with tumour-reactive T cells. Importantly, we showed that chronically activated, tumour-reactive T cells exposed to fibroblast-derived TGF-ß may act as TLS organisers by producing the B cell chemoattractant CXCL13. Identification of highly similar subsets of clonally expanded CXCL13 + tumour-infiltrating T cells across multiple cancer types further indicated a conserved link between tumour-antigen recognition and the allocation of B cells within sheltered hubs in the tumour microenvironment. Finally, we showed that the expression of a gene signature reflecting mature TLSs was enriched in pretreatment biopsies from PDAC patients with longer survival after receiving different chemoimmunotherapy regimens. CONCLUSION: We provided a framework for understanding the biological role of PDAC-associated TLSs and revealed their potential to guide the selection of patients for future immunotherapy trials.

Current Treatment of Potentially Resectable Pancreatic Ductal Adenocarcinoma: A Medical Oncologist's Perspective.

Pancreatic cancer has traditionally been associated with a dismal prognosis, even in early stages of the disease. In recent years, the introduction of newer generation chemotherapy regimens in the adjuvant setting has improved the survival of patients treated with upfront resection. However, there are multiple theoretical advantages to deliver early systemic therapy in patients with localized pancreatic cancer. So far, the evidence supports the use of neoadjuvant therapy for patients with borderline resectable pancreatic cancer. The benefit of this treatment sequence for patients with resectable disease remains elusive. In this review, we summarize the data on adjuvant therapy for pancreatic cancer and describe which evidence backs the use of neoadjuvant therapy. Additionally, we address important issues faced in clinical practice when treating patients with localized pancreatic cancer.

Current clinical practice in the management of Brazilian patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC).

BACKGROUND AND OBJECTIVES: We aimed to describe the routine clinical practice of physicians involved in the treatment of patients with localized pancreatic ductal adenocarcinoma (PDAC) in Brazil. METHODS: Physicians were invited through email and text messages to participate in an electronic survey sponsored by the Brazilian Gastrointestinal Tumor Group (GTG) and the Brazilian Society of Surgical Oncology (SBCO). We evaluated the relationship between variable categories numerically with false discovery rate-adjusted Fisher's exact test p values and graphically with Multiple Correspondence Analysis. RESULTS: Overall, 255 physicians answered the survey. Most (52.5%) were medical oncologists, treated patients predominantly in the private setting (71.0%), and had access to multidisciplinary tumor boards (MTDTB; 76.1%). Medical oncologists were more likely to describe neoadjuvant therapy as beneficial in the resectable setting and surgeons in the borderline resectable setting. Most physicians would use information on risk factors for early recurrence, frailty, and type of surgery to decide treatment strategy. Doctors working predominantly in public institutions were less likely to have access to MTDTB and to consider FOLFIRINOX the most adequate regimen in the neoadjuvant setting. CONCLUSIONS: Considerable differences exist in the management of localized PDAC, some of them possibly explained by the medical specialty, but also by the funding source of health care.

Opportunistic and Serious Infections in Patients with Neuroendocrine Tumors Treated with Everolimus: A Multicenter Study of Real-World Patients.

INTRODUCTION: The incidence of infections is poorly studied in patients with neuroendocrine tumors (NET) treated with everolimus outside of clinical trials. We aimed to evaluate the frequency of and risk factors for opportunistic infections (Opl) or any serious infection in eligible patients. METHODS: This was a retrospective multicenter study of a Latin American cohort of consecutive patients with advanced NET treated with everolimus. Duration of everolimus, comorbidities, Charlson comorbidity score, type of prior treatment, institution, and concurrent immunosuppressive conditions were tested for possible associations with serious (grade 3-5) infections in univariate and multivariable logistic regression models. RESULTS: One hundred eleven patients from 5 centers were included. The median duration of everolimus was 8.9 months. After a median follow-up of 32.9 months, 34 patients (30.6%; 95% CI 22.2-40.1) experienced infections of any grade, with 24 (21.6%; 95% CI 14.8-30.4) having a serious infection and 7 (6.3%; 95% CI 2.6-12.6) having at least 1 OpI (Candida sp., Toxoplasma gondi, Pneumocystis sp., Herpes sp., and Cryptococcus sp.). Four patients (3.6%) died from infections, but only 2 deaths (1.8%) were deemed to be related to everolimus. The multivariable analysis identified everolimus duration (every 6-month increase; OR = 1.28; 95% CI 1.02-1.60; p = 0.03) as an independent risk factor for serious infection. CONCLUSION: Infections are more frequent in NET patients using everolimus than previously reported in clinical trials. Patients on everolimus should be closely monitored for infections, especially those receiving it for several months.

Role of staging laparoscopy in the management of Pancreatic Duct Carcinoma (PDAC): Single-center experience from a tertiary hospital in Brazil.

BACKGROUND: Proper staging is critical to the management of pancreatic ductal carcinoma (PDAC). Laparoscopy has been used to stage patients without gross metastatic disease with variable success. OBJECTIVES: We aimed to identify the frequency of patients diagnosed by laparoscopy with occult metastatic disease. Also, we looked for variables related to a higher chance of occult metastasis. METHODS: Patients with PDAC submitted to staging laparoscopy either immediately before pancreatectomy or as a separate procedure between January 2010 and December 2016 were included. None presented gross metastatic disease at initial staging. We used logistic regression to search for variables associated with metastatic disease. RESULTS: The study population consisted of 63 patients. Among all patients, nine (16.7%) had occult metastases at laparoscopy. Unresectable tumor (Odds ratio = 18.0, P = 0.03), increasing tumor size (Odds ratio = 1.36, P = 0.01), and abdominal pain (Odds ratio = 5.6, P = 0.04) significantly predicted the risk of occult metastases in univariate analysis. In multivariate analysis, only tumor size predicted the risk of occult metastases. CONCLUSION: Laparoscopy remains a valuable tool in PDAC staging. Patients with either large or unresectable tumors, or presenting with abdominal pain present the highest risk for occult intra-abdominal metastases.

Neoadjuvant intraperitoneal chemotherapy followed by radical surgery and HIPEC in patients with very advanced gastric cancer and peritoneal metastases: report of an initial experience in a western single center.

BACKGROUND: The association of preoperative systemic and intraperitoneal chemotherapy has been described in Eastern patients with very good outcomes in treatment responders. The aim of this paper is to describe the initial results of this multidisciplinary regimen in gastric cancer patients with very advanced peritoneal metastases. CASE PRESENTATION: We present here the first four cases who received the treatment protocol. They had a baseline PCI between 19 and 33. Two patients had received systemic chemotherapy prior to this regimen. Three of them had significant response and were taken to cytoreductive surgery, while one patient who had 12 cycles of chemotherapy previously showed signs of disease progression and subsequently died. There was no significant postoperative morbidity, and three patients remain alive, two of them with no signs of recurrence. CONCLUSION: Systemic and intraperitoneal chemotherapy led to a marked response in peritoneal disease extent in our initial experience and allowed three of four patients with very advanced disease to be treated with cytoreductive surgery.

Angiogenesis-related protein expression in bevacizumab-treated metastatic colorectal cancer: NOTCH1 detrimental to overall survival.

BACKGROUND: The development of targeted therapies has undoubtedly broadened therapeutic options for patients with colorectal cancer (CRC). The use of bevacizumab to reduce angiogenesis has been associated with improved clinical outcomes. However, an urgent need for prognostic/predictive biomarkers for anti-angiogenic therapies still exists. METHODS: Clinical data of 105 CRC patients treated with bevacizumab in conjunction with chemotherapy were analyzed. The expression of vascular endothelial growth factor (VEGF) receptors, NOTCH1 receptor and its ligand DLL4 were determined by immunohistochemistry. Tumor samples were arranged on a tissue microarray. The association between protein expression and clinicopathological characteristics and outcomes was determined. RESULTS: Bevacizumab was administered as a first-line of treatment in 70.5 % of our cases. The median progression-free survival (PFS) was 10.2 months. The median overall survival (OS) of the total cohort was 24.4 months. Bevacizumab, as the first-line of treatment, and the presence of liver metastasis were independently associated with objective response rate. Membrane VEGFR1 and VEGFR3 expressions were associated with the presence of lung metastasis; interestingly, VEGFR3 was associated with less liver metastasis. NOTCH1 expression was associated with lymph node metastasis. There was a trend toward association between improved PFS and lower NOTCH1 expression (p = 0.06). Improved OS was significantly associated with lower NOTCH1 expression (p = 0.01). In a multivariate analysis, ECOG (Eastern Cooperative Oncology Group) performance status, liver metastasis, histological grade, and NOTCH1 expression were independently associated with OS. CONCLUSION: Our findings illustrated the expression profile of angiogenesis-related proteins and their association with clinicopathological characteristics and outcomes. NOTCH1 expression is a detrimental prognostic factor in metastatic CRC patients treated with chemotherapy plus bevacizumab.

A narrative review on rare types of pancreatic cancer: should they be treated as pancreatic ductal adenocarcinomas?

Pancreatic cancer is one of the deadliest malignancies in humans and it is expected to play a bigger part in cancer burden in the years to come. Pancreatic ductal adenocarcinoma (PDAC) represents 85% of all primary pancreatic malignancies. Recently, much attention has been given to PDAC, with significant advances in the understanding of the mechanisms underpinning disease initiation and progression, along with noticeable improvements in overall survival in both localized and metastatic settings. However, given their rarity, rare histological subtypes of pancreatic cancer have been underappreciated and are frequently treated as PDAC, even though they might present non-overlapping molecular alterations and clinical behavior. While some of these rare histological subtypes are true variants of PDAC that should be treated likewise, others represent separate clinicopathological entities, warranting a different therapeutic approach. In this review, we highlight clinical, pathological, and molecular aspects of rare histological types of pancreatic cancer, along with the currently available data to guide treatment decisions.

Should rare subtypes of pancreatic cancer be treated as its most common variant (ductal adenocarcinoma)? The most common type of pancreatic cancer is ductal adenocarcinoma. While much attention has been given to the molecular aspects and treatment aspects of this disease, rare variants of pancreatic cancer have been underappreciated. Some of them present unique molecular features that suggest different treatment approaches could lead to better outcomes. In this review, we summarize information on the clinical, pathological, and molecular features of rare subtypes of pancreatic cancer, along with subtype-specific data on treatment.

Claudin 18.2 as a New Biomarker in Gastric Cancer-What Should We Know?

Gastric cancer (GC) remains a formidable global health challenge, ranking among the top-five causes of cancer-related deaths worldwide. The majority of patients face advanced stages at diagnosis, with a mere 6% five-year survival rate. First-line treatment for metastatic GC typically involves a fluoropyrimidine and platinum agent combination; yet, predictive molecular markers have proven elusive. This review navigates the evolving landscape of GC biomarkers, with a specific focus on Claudin 18.2 (CLDN18.2) as an emerging and promising target. Recent phase III trials have unveiled the efficacy of Zolbetuximab, a CLDN18.2-targeting antibody, in combination with oxaliplatin-based chemotherapy for CLDN18.2-positive metastatic GC. As this novel therapeutic avenue unfolds, understanding the nuanced decision making regarding the selection of anti-CLDN18.2 therapies over other targeted agents in metastatic GC becomes crucial. This manuscript reviews the evolving role of CLDN18.2 as a biomarker in GC and explores the current status of CLDN18.2-targeting agents in clinical development. The aim is to provide concise insights into the potential of CLDN18.2 as a therapeutic target and guide future clinical decisions in the management of metastatic GC.

Targeting KRAS in Pancreatic Ductal Adenocarcinoma: The Long Road to Cure.

Pancreatic ductal adenocarcinoma (PDAC) remains an important cause of cancer-related mortality, and it is expected to play an even bigger part in cancer burden in the years to come. Despite concerted efforts from scientists and physicians, patients have experienced little improvement in survival over the past decades, possibly because of the non-specific nature of the tested treatment modalities. Recently, the discovery of potentially targetable molecular alterations has paved the way for the personalized treatment of PDAC. Indeed, the central piece in the molecular framework of PDAC is starting to be unveiled. KRAS mutations are seen in 90% of PDACs, and multiple studies have demonstrated their pivotal role in pancreatic carcinogenesis. Recent investigations have shed light on the differences in prognosis as well as therapeutic implications of the different KRAS mutations and disentangled the relationship between KRAS and effectors of downstream and parallel signaling pathways. Additionally, the recognition of other mechanisms involving KRAS-mediated pathogenesis, such as KRAS dosing and allelic imbalance, has contributed to broadening the current knowledge regarding this molecular alteration. Finally, KRAS G12C inhibitors have been recently tested in patients with pancreatic cancer with relative success, and inhibitors of KRAS harboring other mutations are under clinical development. These drugs currently represent a true hope for a meaningful leap forward in this dreadful disease.

Short-term survival of patients with advanced pancreatic cancer admitted to intensive care unit: a retrospective cohort study.

Background: Little is known about the outcomes of patients with advanced pancreatic cancer admitted to the intensive care unit (ICU) due to medical complications. We designed a study to evaluate their short-term (30-day) survival, predictors of short-term survival and chances of additional chemotherapy. Methods: We reviewed all patients with advanced (stage III or IV) pancreatic adenocarcinoma admitted to an ICU in a dedicated Brazilian cancer centre from 2009 to 2018 due to medical reasons. We fitted multivariate regression models to identify predictors of 30-day survival and additional systemic chemotherapy. Results: The study population consisted of 171 patients. Ninety-four patients (55.0%) had Eastern Cooperative Oncology Group (ECOG) performance status 2-4 and 146 (85.4%) had metastatic disease. Most patients (N = 75; 43.9%) were admitted to the ICU during first-line treatment. Median overall survival was 32 days (95% confidence interval (95% CI): 20-49). Survival rate at 30 days was 50.6%. ECOG performance status 2-4 was the only variable associated with lower probability of survival at 30 days in multivariate analysis (odds ratio: 0.28; 95% CI: 0.14-0.54; p < 0.001). Overall, 58 patients (33.9%) received additional chemotherapy and among all patients, 13.5% experienced clinical benefit from this treatment. Conclusion: Patients with advanced pancreatic cancer admitted to the ICU for medical reasons have a dismal prognosis. Early palliative care and refined tools to establish those who would benefit from an ICU trial could help improve patients' care.

Current Molecular Profile of Gastrointestinal Stromal Tumors and Systemic Therapeutic Implications.

Gastrointestinal stromal tumors (GISTs) are malignant mesenchymal tumors arising from the intestinal pacemaker cells of Cajal. They compose a heterogenous group of tumors due to a variety of molecular alterations. The most common gain-of-function mutations in GISTs are either in the KIT (60-70%) or platelet-derived growth factor receptor alpha (PDGFRA) genes (10-15%), which are mutually exclusive. However, a smaller subset, lacking KIT and PDGFRA mutations, is considered wild-type GISTs and presents distinct molecular findings with the activation of different proliferative pathways, structural chromosomal and epigenetic changes, such as inactivation of the NF1 gene, mutations in the succinate dehydrogenase (SDH), BRAF, and RAS genes, and also NTRK fusions. Currently, a molecular evaluation of GISTs is imperative in many scenarios, aiding in treatment decisions from the (neo)adjuvant to the metastatic setting. Here, we review the most recent data on the molecular profile of GISTs and highlight therapeutic implications according to distinct GIST molecular subtypes.

Evaluation of prognostic factors in patients undergoing first-line chemotherapy for advanced biliary tract cancer: a retrospective analysis from a South American cancer centre.

INTRODUCTION: Biliary tract cancers (BTCs) are rare tumours with regional differences. Prognostic factors are poorly understood. Gemcitabine + platinum (GP) is the standard first-line chemotherapy in metastatic patients. We aimed to search for prognostic factors in patients with advanced disease in a cancer centre in South America. METHODS: We conducted a retrospective analysis of patients with advanced BTC treated with chemotherapy. Variables were age (< or ≥70 years), Eastern Cooperative Oncology Group (ECOG) performance status (0/1 versus 2/3), gender, primary site (intrahepatic (IHC), extrahepatic (EHC), gallbladder (GB)), staging (locally advanced versus metastatic), metastatic sites, albumin (>3.5 g/dL versus <3.5 g/dL), biliary obstruction and first-line chemotherapy (GP, 5FU-based or single-agent). Cox regression method was used to explore factors. RESULTS: From 2010 to 2017, 104 patients were included. Median age was 62 years (32-86) and 22.1% were older than 70 years. Most patients had ECOG performance status 0/1 (63.4%), were female (51.9%) and were metastatic (82.7%). Bone metastases were found in 19.2%. Primary IHC, EHC and GB were 54.8%, 36.5% and 8.7%, respectively. GP was used by 79.8%. Median follow-up was 32.4 months. Median overall survival (mOS) was 11.4 months. In univariate analysis, male (p = 0.007), albumin < 3.5 g/dL (p = 0.001), biliary obstruction (p = 0.006), 5FU-based (p = 0.006) and single-agent (p < 0.0001) were associated with worse OS. ECOG performance status 2/3 (p = 0.058) and bone metastases (p = 0.051) were marginally related. In multivariate analysis, male (p = 0.003), bone metastases (p = 0.023), biliary obstruction (p = 0.001), 5FU-based (p = 0.016) and single-agent (p = 0.023) were independently associated with inferior OS. CONCLUSION: In this retrospective study, we observed that male patients, bone metastases, biliary obstruction and regimens other than GP had worse survival. Larger studies should be conducted to confirm our findings.

Erratum: Comparative efficacy of modified FOLFIRINOX, gemcitabine plus capecitabine and gemcitabine plus nab-paclitaxel as adjuvant treatment for resected pancreatic cancer: a Bayeasian network meta-analysis.

[This corrects the article on p. 1 in vol. 15.].

Comparative efficacy of modified FOLFIRINOX, gemcitabine plus capecitabine and gemcitabine plus nab-paclitaxel as adjuvant treatment for resected pancreatic cancer: a Bayesian network meta-analysis.

BACKGROUND: There are no head-to-head comparisons evaluating the efficacy of the main polychemotherapy regimens used for patients with pancreatic cancer in the adjuvant setting. We aimed to describe the relative efficacy of modified FOLFIRINOX (mFOLFIRINOX), gemcitabine plus capecitabine (GEM-CAP) and gemcitabine plus nab-paclitaxel (GEM-NAB) in this setting using a Bayesian network approach. METHODS: We collected data from the ESPAC-4, PRODIGE 24 and APACT trials. Disease-free survival (DFS), according to the investigators, and overall survival (OS) for the three polychemotherapy regimens were compared using gemcitabine as the reference arm. We ran Markov chain Monte Carlo simulations with a fixed-effect model to generate the posterior distribution of the hazard ratios (HRs) using non-informative priors. Relative efficacy was measured by HRs, surface under cumulative ranking and rankograms. RESULTS: mFOLFIRINOX was the chemotherapy regimen most likely to be the most effective in the adjuvant setting (98.9% and 89.6% probability for DFS and OS, respectively). GEM-NAB marginally improved DFS (HR = 0.97, 95% credible interval (95% CrI) = 0.77-1.21) and OS (HR = 0.98, 95% CrI = 0.76-1.25) when compared to GEM-CAP. However, GEM-NAB had the highest chances of being the second most active chemotherapy regimen (61.4% and 52.5% probability for DFS and OS, respectively), whereas GEM-CAP was less likely to represent the second most active regimen (37.7% and 40.1% probability for DFS and OS, respectively). CONCLUSION: For patients eligible and fit enough to undergo adjuvant treatment with mFOLFIRINOX, this constitutes the treatment of choice. For those with contraindications to mFOLFIRINOX, while both GEM-NAB and GEM-CAP can be considered appropriate alternatives, GEM-NAB is likely the most effective regimen.

Disparities in access to health care system as determinant of survival for patients with pancreatic cancer in the State of São Paulo, Brazil.

Little is known about the features and outcomes of Brazilian patients with pancreatic cancer. We sought to describe the socio-economic characteristics, patterns of health care access, and survival of patients diagnosed with malignant pancreatic tumors from 2000 to 2014 in São Paulo, Brazil. We included patients with malignant exocrine and non-classified pancreatic tumors according to the International Classifications of Disease (ICD)-O-2 and -O-3, diagnosed from 2000 to 2014, who were registered in the FOSP database. Prognostic factors for overall survival (OS) in the subgroup of patients with ductal or non-specified (adeno)carcinoma were evaluated using Cox proportional hazard model. The study population consists of 6855 patients. Median time from the first visit to diagnosis and treatment were 13 (Interquartile range [IQR] 4-30) and 24 (IQR 8-55) days, respectively. Both intervals were longer for patients treated in the public setting. Median OS was 4.9 months (95% confidence interval [95% CI] 4.7-5.2). Increasing age, male gender, lower educational level, treatment in the public setting, absence of treatment, advanced stage, and treatment from 2000 to 2004 were associated with inferior OS. From 2000-2004 to 2010-2014, no improvement in OS was seen for patients treated in the public setting. Survival of patients with malignant pancreatic tumors remains dismal. Socioeconomical variables, especially health care funding, are major determinants of survival. Further work is necessary to decrease inequalities in access to medical care for patients with pancreatic cancer in Brazil.

Clinical factors related to severe enterocolitis after adjuvant CAPOX for colorectal cancer: a retrospective analysis.

BACKGROUND: CAPOX regimen is a standard option in stage III adjuvant colon cancer. Gastrointestinal toxicity is well described with fluoropyrimidine regimens and can be life-threatening. Identification of risk factors associated with severe gastrointestinal toxicity may help clinicians when choosing the adjuvant regimen. MATERIALS AND METHODS: We retrospectively analysed 61 patients treated with adjuvant CAPOX. Our primary objective was to estimate the incidence of severe chemotherapy-induced enterocolitis among patients treated with CAPOX. A secondary objective was to describe the main demographic and clinical characteristics of these patients. A univariate logistic regression was performed to estimate the odds ratio (OR) with a 95% CI to identify a predictor for severe enterocolitis. RESULTS: Grade 3 diarrhoea was reported in 10 patients (16.3%). Admissions to hospital due to toxicity occurred in nine cases. Reasons for hospitalisation were severe enterocolitis in eight cases (13.1%) and rectal bleeding plus thrombocytopenia in one case. Age > 70 years (OR 9.6; 95% CI 1.81-50.6; p = 0.008), primary surgery involving right/transverse colon (OR 16.8; 95% CI 2.88-98.8; p = 0.002) and Angiotensin II Receptor Blocker (ARB) use (OR 8.14; 95% CI 1.64-40.3; p = 0.010) were associated with severe enterocolitis. CONCLUSION: Our data showed that adjuvant CAPOX induced severe enterocolitis in 13.1% of patients. In addition, we found that advanced age, right colectomy and concurrent use of ARB were statistically associated with these events. Awareness of these factors could be easily incorporated into the treatment decision and patient orientation.

Primary Tumor Location Is a Predictor of Poor Prognosis in Patients with Locally Advanced Esophagogastric Cancer Treated with Perioperative Chemotherapy.

BACKGROUND: Esophagogastric cancer (EGC) is a leading neoplasm worldwide. Perioperative chemotherapy (periCT) is currently a standard of care for most patients (pts). Prevalence of esophagogastric junction (EGJ) tumors is increasing over the last years. METHODS: The aim of this study was to retrospectively search for prognostic factors in pts. with locally advanced EGC treated with periCT. Three-year overall survival (OS) and Event-Free Survival (EFS) were main end-points. HER-2 positive tumors were defined by immunohistochemistry or FISH. RESULTS: Between June/2007 and November/2015, 128 pts. started periCT for esophagogastric junction (EGJ) or gastric adenocarcinoma (GC). Median age was 59.5 y and 64% were male. Primary site was EGJ in 27% and 65% were cN+. Diffuse subtype was seen in 42%. Ninety-seven pts. were assessed for HER-2; 14 (14.4%) were positive. After median follow-up time of 45 m, 48 deaths occurred. The 3-year OS and EFS rate was 61.3% and 51.2%, respectively. Main prognostic factors were: AJCC ypT3-T4yN1-N3 (HR 6.75 p 0.002) and EGJ primary (HR 2.64, p 0.004). Overall HER-2 was not prognostic. Still, a difference in 3-year OS was observed for GC/HER2+ compared to EGJ/HER2+ (88.9% versus 20%, p = 0.002). This difference is greater for 3-year EFS with no patient with EGJ/HER2+ free-of-event against 62.5% for GC/HER+ (p = 0.011). CONCLUSION: In our analysis, pathological staging and primary site were main prognostic factors. Moreover, a small group of EGJ/HER2+ had very poor survival.

Characteristics and survival of older patients with metastatic pancreatic cancer: a retrospective analysis of the AC Camargo Cancer Center experience.

BACKGROUND: Advanced age is the most important risk factor for pancreatic cancer and about half of patients are diagnosed with metastatic disease. In the first-line setting, multidrug chemotherapy regimens were shown to be more effective than gemcitabine alone. However, the older population was under-represented in randomized clinical trials. We aimed to describe the clinical profile of older patients with metastatic pancreatic cancer and their survival outcomes. MATERIALS AND METHODS: This was a retrospective, unicentric study that included patients diagnosed with metastatic pancreatic cancer (non-neuroendocrine), aged 65 years and over. RESULTS: The study population comprised 196 patients. The median age was 73 years; 67% of these patients presented Eastern Cooperative Oncology Group performance status (ECOG) ⩽ 1 and the median Charlson Comorbidity score was 10. Chemotherapy was given to 89% of the patients. The most frequently used chemotherapy regimens were gemcitabine (44%), 5-fluorouracil and oxaliplatin [FOLFOX; 26%], and 5-fluorouracil, oxaliplatin and irinotecan (FOLFIRINOX; 20%). Patients treated with FOLFIRINOX were younger and they presented better performance status. After a median follow up of 19.8 months, the median overall survival (OS) was of 7.2 months and the median time to first-line-treatment failure was 4.6 months. Among patients treated with chemotherapy, the median OS was highest for those treated with FOLFIRINOX (13.8 months), as compared with FOLFOX (7.0 months) or gemcitabine (6.7 months); p = 0.004. Nonetheless, treatment with FOLFIRINOX was associated with increased risk of severe toxicity (p = 0.008). CONCLUSION: Older patients with metastatic pancreatic cancer benefit from palliative chemotherapy, and FOLFIRINOX is a therapeutic option in rigorously selected older patients.

A modified recursive partitioning analysis for predicting overall survival in patients with non-small cell lung cancer and central nervous system metastases.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a major cause of brain metastases. Nonetheless, patients with central nervous system (CNS) spread are poorly represented in clinical trials. We sought to evaluate the overall survival (OS) of patients with NSCLC and CNS metastases. METHODS: Patients with NSCLC and CNS metastases treated at A. C. Camargo Cancer Center from January 2007 to December 2017 were selected. The primary endpoint was OS following the diagnosis of CNS metastasis. The Kaplan-Meier method was applied to calculate OS. Prognostic factors were assessed by the Cox Proportional Hazards model. As an exploratory analysis, a survival tree was generated based upon the two most statistically significant variables in the multivariate model and one additional clinically meaningful variable. RESULTS: In total, 311 patients were included. Median OS was 10.3 months (95% CI, 8.7-13.1 months). ECOG performance status 2-4 (HR 2.12; 95% CI, 1.40-3.20; P<0.01) and the absence of a driver mutation (HR 3.30; 95% CI, 1.85-5.90; P<0.01) were strongly associated with worse OS. A Modified Recursive Partitioning Analysis (mRPA) was developed based on the curves generated by the survival tree. mRPA stratified our cohort in four subgroups with significantly different OS (3.1 to 43 months) and it outperformed both RPA and GPA in predicting OS in our population. CONCLUSIONS: OS in our cohort was better than previously reported. However, prognosis is widely variable and is mostly dictated by performance status and the presence of a driver mutation.