Nivolumab plus ONC201 plus in microsatellite stable (MSS) metastatic colorectal cancer (mCRC) patients: a Brown University Oncology Research Group phase Ib/II study (BrUOG379).

Background: Immune checkpoint inhibitors alone, or in combination with chemotherapy failed to provide meaningful clinical activity for patients with microsatellite stable (MSS) colorectal cancer (CRC). ONC201 is a small molecule that inactivates AKT and ERK signaling and actives the TRAIL pathway. Preclinical studies indicated potential benefits of combining ONC201 with checkpoint inhibitors. This is a phase Ib/II trial of ONC201 plus nivolumab for patient with MSS CRC who progressed on standard treatment. Methods: Enrolled patients received ONC201 plus nivolumab in a dose de-escalation fashion to determine the maximum tolerated dose (MTD). Additional patients were enrolled in the dose-expansion cohort. ONC201 at a dose of 625 mg was given orally at day -7 of cycle 1, followed by weekly dosing. Nivolumab was given every 2 weeks at 240 mg IV starting on day 1 of every cycle (cycle =28 days). The primary end point was dose-limiting toxicity (DLT) during the observation window (run-in dose day -7, cycle 1 to assessment pre-dosing cycle 2). The plan was to enroll 28 additional patients at the MTD so that a total of 34 patients would be treated at the MTD. Pharmacokinetics (PKs) and tumor biopsies were collected at several time points per study protocol. Results: A total of 13 patients (8 patients in the dose escalation *6 evaluable*) were enrolled between December 4, 2019 and March 2021. All patients had received ≥2 previous lines of chemotherapy and had confirmed microsatellite stability or mismatch repair-proficient tumors. No DLTs were observed with 625 mg ONC201 in the first three patients. Three additional patients were enrolled at the same dose to confirm safety. Two patients progressed during the DLT period and had to be replaced. During the dose-expansion part, five patients were enrolled and none required dose reduction or modification. No objective tumor response was observed in the 13 treated patients. Disease progression was confirmed at the time of the first imaging evaluation at 8 weeks following cycle 2. Post discussion at the Data and Safety Monitoring Board (DSMB) on May 25, 2021, the principal investigator (PI) and Committee voted to close the study to new patient enrollment prior to reaching accrual of 34 patients, secondary to lack of efficacy. Conclusions: In this study of patients with advanced MSS CRC, combination ONC201/nivolumab was well-tolerated; objective responses to ONC201/nivolumab were not observed.

Selection of Germline Genetic Testing Panels in Patients With Cancer: ASCO Guideline.

PURPOSE: To guide use of multigene panels for germline genetic testing for patients with cancer. METHODS: An ASCO Expert Panel convened to develop recommendations on the basis of a systematic review of guidelines, consensus statements, and studies of germline and somatic genetic testing. RESULTS: Fifty-two guidelines and consensus statements met eligibility criteria for the primary search; 14 studies were identified for Clinical Question 4. RECOMMENDATIONS: Patients should have a family history taken and recorded that includes details of cancers in first- and second-degree relatives and the patient's ethnicity. When more than one gene is relevant based on personal and/or family history, multigene panel testing should be offered. When considering what genes to include in the panel, the minimal panel should include the more strongly recommended genes from Table 1 and may include those less strongly recommended. A broader panel may be ordered when the potential benefits are clearly identified, and the potential harms from uncertain results should be mitigated. Patients who meet criteria for germline genetic testing should be offered germline testing regardless of results from tumor testing. Patients who would not normally be offered germline genetic testing based on personal and/or family history criteria but who have a pathogenic or likely pathogenic variant identified by tumor testing in a gene listed in Table 2 under the outlined circumstances should be offered germline testing.Additional information is available at www.asco.org/molecular-testing-and-biomarkers-guidelines.

Palliative care tumor board: a narrative review and presentation of a novel conference to enhance collaboration and coordination of pain and symptom management for patients with advanced cancer.

BACKGROUND AND OBJECTIVE: The World Health Organization endorses that palliative care has a significant impact on the outcomes of patients with cancer. Integration of palliative care into standard oncology practice has been shown to improve a variety of patient outcomes. In this article, we present our experience with the development of a palliative care tumor board. METHODS: Starting in June 2021, we implemented a multidisciplinary palliative care and oncology tumor board focused on pain and symptom management. Complex cases were presented bimonthly. We retrospectively reviewed our experience. Data were collected on the attendees, the case presented, and the resultant therapeutic decisions made. KEY CONTENT AND FINDINGS: Between June 2021 and September 2022, tumor board meetings were conducted in person and virtually. An average of twelve people attended, including physicians and nurse practitioners from the palliative care, oncology, interventional radiology, radiation oncology, psychiatry, pediatric palliative care, and physical medicine and rehab disciplines. There were 68 patients presented with the most frequently discussed cancer being breast cancer, followed by lung cancer. A total of 18 patients (26%) were referred for procedure, including 7 patients (10%) for radiation and 11 patients (16%) for interventional procedures, and 34 patients (50%) had medication changes as outcomes of the meeting. CONCLUSIONS: The development of a biweekly palliative care conference modeled after traditional oncologic tumor board meetings allows patients to be discussed in a multidisciplinary setting and commonly results in changes in the management for pain and other cancer-related symptoms.

Palliative care for patients with gastroesophageal cancer at all stages: a narrative review.

BACKGROUND AND OBJECTIVE: Gastroesophageal junction (GEJ) cancer is a highly morbid disease with a poor prognosis. While uncommon in the United States, globally it is ranked as the sixth or seventh most common cancer depending on survey tool. GEJ cancer presents a unique and challenging symptom profile for patients at all disease stages, regardless of histology. Even patients with early stage disease experience debilitating cancer-related symptoms and treatment side effects. The heavy symptom burden associated with this disease includes dysphagia, nausea and vomiting, pain, anxiety, depression and malnutrition. These symptoms require a multidisciplinary approach involving local therapies including radiation and stent placement, systemic cancer-directed therapy, nutritional support, and supportive medical management. This review aims to examine the unique symptom burden experienced by patients with GEJ cancer and provide an updated overview of symptom management techniques. METHODS: A PubMed search was conducted using the terms "gastroesophageal junction cancer AND palliative care". Articles published from 2008 to 2022 with a primary focus on supportive care for patients with GEJ cancers were reviewed. KEY CONTENT AND FINDINGS: A total of 119 articles were identified and screened in our database search. Of these, 22 full text articles met inclusion criteria and were reviewed. Seventeen articles addressed technical interventions for the alleviation of dysphagia, 1 article focused on nutrition, 1 article described the impact of multidisciplinary tumor boards, 1 article presented the effect of home nurse visits, 1 article described the use of antiemetics, and 1 article was a narrative review of supportive care. CONCLUSIONS: In this narrative review, we examine specific supportive care needs in the GEJ cancer population. While the predominant symptom addressed in the literature is dysphagia, patients with GEJ cancer carry a complex symptom burden from diagnosis, through cancer-directed therapy to end-of-life care. Early referral to specialty palliative care should be considered for all patients with GEJ cancer to foster symptom management and delivery of goal concordant care.

Is every psychiatrist an oncology psychiatrist?-Special needs for special populations: a scoping review.

BACKGROUND: The evolution of psychiatric care for patients with cancer has played out over the last century. The first collaboration of psychiatry, oncology surgery, and radiation-oncology occurred in the mid-1950s and represented the early seeds of psycho-oncology. The role of a psychiatrist specializing in treating patients with cancer, a psychosocial oncologist or psycho-oncologist, spans the care continuum from prevention to end of life. The specific needs of patients with gastrointestinal (GI) malignancies range from management of anxiety and depression to focused management for adjustment to an ostomy to sexual dysfunction to treatment in the face of a neuroendocrine tumor (NET). METHODS: This is a scoping review; we compiled and summarized psychiatric illnesses commonly encountered in care of patients with cancer in addition to unique GI oncology-related issues. We conducted an electronic PubMed search between 1990-2022. We are presenting the data and providing our insight into psychosocial oncology care for this special population. RESULTS: The field of psycho-oncology is relatively new. We failed to identify any randomized prospective studies, the majority of the studies were retrospective or longitudinal. The majority of the publications were in the form of review. We reviewed the GI literature to identify the psychological impact of ostomies, sexual impairment and metabolically active NETs. We provide suggested treatment interventions targeting the biological, psychological, and social aspects of patient and family lives. CONCLUSIONS: The role of a psychosocial oncologist as part of the collaborative multidisciplinary treatment team provides nuanced care with attention to unique cancer-related issues that arise during the disease course. The psycho-oncologist brings expertise in combining targeted therapeutic strategies with pharmacologic interventions to address the multi-dimensional symptomatology patients experience. Using a layered approach, patients with mild symptoms can be supported by the general team, while those with moderate to severe symptoms require specialty psychiatric consultation.

Characterizing after-hours hematology/oncology clinic calls.

BACKGROUND: After-hour calls can be resource intensive and remain a significant challenge to medical practices, though they have historically been poorly or non-reimbursable services. This study reviews after-hour calls from hematology/oncology patients at a cancer center to characterize after-hour care needs, identify care gaps, and look for opportunities to improve outpatient healthcare delivery. METHODS: This descriptive, retrospective Institutional Review Board-approved study analyzed patient calls between June 2015 to February 2021 in an academic hematology/oncology practice. Data from 500 calls were reviewed and cataloged into a database including patient demographics, clinical history, and information surrounding the call (e.g., primary reason for the call, outcome of the call). Calls were also categorized as being urgent or not from a patient or provider's perspective. RESULTS: Among 500 calls, representing 398 unique patients, the average patient was 62 years old and 52% of calls were from females. Most calls were made to report symptoms (65%), followed by calls to follow-up on labs, tests, or imaging (13%), and clarifying treatment plans (10%). Oncology patients represented 67% of calls and hematology (malignant and benign) patients represented 33%. More specifically, patients with gastrointestinal cancer (25%), hematologic malignancies (24%), and thoracic cancer (13%) represented the diagnoses with the highest call volume. CONCLUSIONS: This study explores the complexity and variety of after-hour cancer patient calls. By systematically exploring patient calls, this data can provide insight into patients' needs outside of regular clinic times and help practices develop strategies to anticipate these needs, reduce after-hour call burden, and improve overall quality of care.

Total parenteral nutrition for patients with gastrointestinal cancers: a clinical practice review.

The use of total parenteral nutrition (TPN) in patients with gastrointestinal cancers is a well-established practice, yet there is substantial variability in its use across institutions. Decision-making around the initiation of TPN is complex. An interdisciplinary team can help identify patient factors and clinical situations that influence whether a patient is likely to benefit from parenteral nutrition. We present the case of a woman with a gastrointestinal cancer who benefited from the initiation of TPN as a bridge therapy to further cancer treatment. This case highlights the importance of establishing a plan for nutrition with specific goals in mind, such as optimizing patients for more cancer-directed therapy. Although patients with gastrointestinal cancers may be candidates for TPN, many patient-specific factors, such as functional status and opportunities for future treatments, must be considered prior to the initiation of parenteral nutrition. An interdisciplinary approach should be used to make recommendations based on patient goals, with a focus on patient and cancer characteristics that are associated with positive outcomes after initiation of TPN. These characteristics include functional status, nutritional status, degree of symptom control, and ability to safely administer nutrition. It is important to continually assess whether parenteral nutrition is beneficial in respect to a patient's preferences and prognosis.

Palliative care in colorectal and anal malignancies from diagnosis to death.

Colorectal (CRC) and anal (AC) cancer, both lower gastrointestinal (GI) cancers vary in their presentation and treatment. Overall, the incidence of CRC has decreased. However, the incidence of CRCs in younger adults has increased over the last 5 years. The incidence of ACs has increased, too. Women are disproportionally impacted by AC which is frequently associated with human papilloma virus (HPV). Patients diagnosed with both cancers often experience multiple symptoms including pain, constipation, nausea, and vomiting. Psychosocial distress including embarrassment and shame often results from both the cancers itself as well as surgical procedures such as creation of ostomy. Palliative care (PC) is an emerging specialty that focuses on maximizing the quality of life (QOL) for patients through expert symptom assessment and management, psychosocial support, and improved communication around illness. The evidence to support earlier integration of PC has steadily increased over the last ten years. The literature shows that early involvement of PC for these populations can result in improved QOL, improved symptom control and decreased intensity of care at the end of life. This article will review the palliative needs of patients diagnosed with CRC and discuss how PC as a specialty is well poised to support these needs.

Advance care planning, serious illness communication, and conversations to facilitate coping for patients with gastrointestinal malignancies: a narrative review.

BACKGROUND AND OBJECTIVE: Patients with advanced gastrointestinal (GI) malignancies are at high-risk for disease-related complications, treatment-related toxicity, unplanned hospitalizations, poor psychological outcomes, and short life-expectancies. Advance care planning (ACP) and serious illness communication (SIC) are two forms of communication that can help patients with GI malignancies explore the future, especially in the event of worsening health. While there are some limitations to traditional ACP, SIC that focuses on what matters most to patients with GI malignancies in the future (future-focused SIC), has the potential to improve future medical decision-making, help patients cognitively and emotionally process and accept their illness over time, help them feel heard and understood, allow them to positively cope with their disease, and may also help their caregivers in a variety of ways. METHODS: Narrative review using PubMed and Google Scholar to search for relevant literature published between 2010-2022. KEY CONTENT AND FINDINGS: We present several key studies that highlight the complex, heterogenous nature of ACP and SIC research and its mixed outcomes for patients with GI malignancies. We also offer suggestions on how to optimize future-focused SIC research in this patient population. In the second half of this article, we suggest a practical approach to conducting future-focused SIC for patients with GI malignancies which includes a communication framework based on the literature and expert-opinion. We also provide practical tips on how to normalize these conversations and how to help patients use these conversations for future medical decision-making. CONCLUSIONS: Future-focused SIC has the potential to benefit patients with advanced GI malignancies in a variety of ways. Optimizing research outcome measures that highlight the patient experience with this communication is crucial to move this area of research forward.

Spiritual care for adult patients with cancer: from maintaining hope and respecting cultures to supporting survivors-a narrative review.

BACKGROUND AND OBJECTIVE: Spirituality is an essential part of being human and spiritual needs are common among patients with serious illness. We will show 'Why' an interdisciplinary approach to spiritual care in adult oncology is the most effective way to support patients' spiritual needs. We will articulate 'Who' from the treatment team should provide spiritual support. We will review a means of 'How' the treatment team can provide spiritual support through being attentive to the spiritual needs, hopes, and resources of adult patients with cancer. METHODS: This is a narrative review. We conducted an electronic PubMed search from 2000-2022 using the following sets of terms: Spirituality, Spiritual Care, Cancer, Adult, Palliative Care. We also incorporated case studies as well as the experience and expertise of the authors. KEY CONTENT AND FINDINGS: Many adult patients with cancer report spiritual needs and a desire for the treatment team to address their spiritual needs. Addressing the spiritual needs of patients has been shown to be beneficial. Yet, the spiritual needs of patients with cancer are infrequently addressed in medical settings. CONCLUSIONS: Adult patients with cancer experience a range of spiritual needs throughout the disease trajectory. Best practice dictates the interdisciplinary treatment team should address the spiritual needs of patients with cancer through a generalist and specialist spiritual care model. Addressing spiritual needs helps patients maintain hope, assists clinicians in sustaining cultural humility during times of medical decision-making, and promotes well-being among survivors.

Current and Emerging Therapeutic Targets for the Treatment of Cholangiocarcinoma: An Updated Review.

Cholangiocarcinoma is a malignancy of the bile ducts that is often associated with late diagnosis, poor overall survival, and limited treatment options. The standard of care therapy for cholangiocarcinoma has been cytotoxic chemotherapy with modest improvements in overall survival with the addition of immune checkpoint inhibitors. The discovery of actionable mutations has led to the advent of targeted therapies against FGFR and IDH-1, which has expanded the treatment landscape for this patient population. Significant efforts have been made in the pre-clinical space to explore novel immunotherapeutic approaches, as well as antibody-drug conjugates. This review provides an overview of the current landscape of treatment options, as well as promising future therapeutic targets.

Immune Checkpoint Inhibitors for Gastrointestinal Malignancies: An Update.

Gastrointestinal (GI) malignancies are a heterogenous group of cancers with varying epidemiology, histology, disease course, prognosis and treatment options. Immune checkpoint inhibitors (ICIs) have changed the landscape of modern cancer treatment, though they have demonstrated survival benefit in other solid tumors more readily than in GI malignancies. This review article presents an overview of the landscape of ICI use in GI malignancies and highlights recent updates in this rapidly evolving field.

The Brown University Oncology Group Experience With FOLFOX + Nab-paclitaxel [FOLFOX-A] for Metastatic and Locally Advanced Pancreatic, BrUOG-292 and BrUOG-318.

OBJECTIVES: To evaluate response rate, toxicity, and efficacy of the novel combination of nab-paclitaxel, oxaliplatin, 5-fluorouracil, and leucovorin [FOLFOX-A] in patients with advanced pancreatic ductal adenocarcinoma [PDAC]. METHODS: BrUOG-292 and BrUOG-318 were two concurrently run, prospective, single-arm phase II studies evaluating FOLFOX-A as first-line therapy in patients with metastatic and locally advanced/borderline resectable PDAC respectively. The FOLFOX-A regimen consisted of 5-fluorouracil, 1200 mg/m 2 /d as a continuous intravenous (IV) infusion over 46 hours, leucovorin 400 mg/m 2 IV, oxaliplatin 85 mg/m 2 IV, and nab-paclitaxel 150 mg/m 2 IV on day 1 every 14 days up to a maximum of 12 cycles. Patients with locally advanced or borderline resectable disease were permitted to stop treatment after 6 cycles and receive radiation therapy and/or surgical exploration if feasible. The primary end point was overall response rate [ORR]. Secondary end points were median progression-free survival [PFS], median overall survival [OS], and safety. RESULTS: Seventy-eight patients with previously untreated PDAC were enrolled between June 2014 and November 2019; 76 patients were evaluable. The median follow-up was 40 months and 32 months, respectively. overall response rate was 34%. Among the patients enrolled on BrUOG-292 [48 patients], the PFS was 5 months and OS was 11 months, respectively. For those enrolled on BrUOG 318 [28 patients], the PFS was 11 months and OS was 22 months. Treatment-related toxicities included grade 3 fatigue [40%], diarrhea [14%], and neuropathy [2%]. CONCLUSIONS: The combination of FOLFOX-A has promising activity in PDAC and may represent an alternative to FOLFIRINOX when reduction of gastrointestinal toxicity is required.

Apatinib in the treatment of gastric cancer in Henan Province: a multicenter prospective real-world observational study (Ahead-HAP01).

Background: Apatinib is approved in China for the treatment of advanced gastric adenocarcinoma that had progressed or relapsed after standard systemic chemotherapy treatments. However, the effectiveness of Apatinib under real-world condition has not been evaluated and the drug performance under ideal and controlled circumstances has not been validated. In fact, genetic factors, poor healthcare access, social economic status, comorbidities compliance and other factors play significant role in drug performance under "real-world" conditions. Real-world experience can help validate the safety and efficacy of apatinib. Methods: In this observational, prospective study we evaluated the safety and efficacy of Apatinib in patient treated in China. Between March 2018 and March 2019, a total of 943 patients with gastric cancer treated with Apatinib were enrolled. Response Evaluation Criteria in Solid Tumors, version 1.1 and Common Terminology Criteria for Adverse Events, version 4.0 were used to evaluate efficacy and adverse effects. Results: The median progression-free survival (PFS) was 5.65 months (5.22-6.05 months), and the median overall survival (OS) was 11.47 months (10.41-12.52 months). Apatinib in combination with more than two agents was superior to single agent apatinib in overall response rate (ORR) [18.18% vs. 9.43%, 95% confidence interval (CI): 1.03-5.90] and disease control rate (DCR) (82.82% vs. 77.87%, 95% CI: 1.21-2.59). Apatinib in combination with single agent chemotherapy was also superior to apatinib alone with DCR (86.29% vs. 77.87%, 95% CI: 1.47-2.99) irrespective of the dose (250 or 500 mg). In the patient cohort who received a starting dose of 250 mg, the DCRs of the combined treatment and monotherapy groups were 86.22% vs. 80.00% (95% CI: 1.18-3.09), respectively. The most common treatment-emergent adverse events were anemia, anorexia and thrombocytopenia (66.28%, 37.75%, 36.06%, respectively). Conclusions: Efficacy of Apatinib in this observational study is promising and toxicities are manageable. Combination of Apatinib with chemotherapy agents has a higher response rate and better disease control at the expense of increased serious adverse events. Better OS can be achieved by receiving apatinib treatment earlier. As a supplement and further validation of explanatory randomized controlled trials, the real-world study reflects the real efficacy of apatinib in practical application.

Beyond Chemotherapy, PD-1, and HER-2: Novel Targets for Gastric and Esophageal Cancer.

Together, gastric cancer and esophageal cancer (EC) possess two of the highest incidence rates amongst all cancers. They exhibit poor prognoses in which the 5-year survival rate is dismal. In addition to cytotoxic chemotherapy, treatment efforts have been geared toward targeting human epidermal growth factor receptor 2 (HER-2), vascular endothelial growth factor (VEGF), and programmed death ligand-1 (PD-1). Although ample success has been recorded with these agents, gastric and esophageal cancer remain lethal, and further research into potential treatment alternatives is needed. In this article, we will review some of the targets at the forefront of investigation such as claudin, Dickkopf-related protein 1 (DKK-1), fibroblast growth factor receptor (FGFR), and matrix metalloproteinases (MMPs). These innovative target pathways are in the midst of clinical trials to be implemented in the treatment algorithm for this patient population. Ultimately, exploiting the oncogenic tendencies of these potential biomarkers creates an opportunity for precise treatment and improved prognosis for these cancers. Lastly, research aimed toward reversing PD-1 antibodies resistance by combining it with other novel agents or other treatment modalities is underway in order to expand existing treatment options for this patient population.

Vaccines in Gastrointestinal Malignancies: From Prevention to Treatment.

Gastrointestinal (GI) malignancies are some of the most common and devastating malignancies and include colorectal, gastric, esophageal, hepatocellular, and pancreatic carcinomas, among others. Five-year survival rates for many of these malignancies remain low. The majority presents at an advanced stage with limited treatment options and poor overall survival. Treatment is advancing but not at the same speed as other malignancies. Chemotherapy and radiation treatments are still only partially effective in GI malignancies and cause significant side effects. Thus, there is an urgent need for novel strategies in the treatment of GI malignancies. Recently, immunotherapy and checkpoint inhibitors have entered as potential new therapeutic options for patients, and thus, cancer vaccines may play a major role in the future of treatment for these malignancies. Further advances in understanding the interaction between the tumor and immune system have led to the development of novel agents, such as cancer vaccines.

Evaluation of the reporting quality of guidelines for gastric cancer using the RIGHT checklist.

BACKGROUND: Gastric cancer is the fifth most common type of cancer globally. We aimed to evaluate the reporting quality of clinical practice guidelines in the field of gastric cancer. METHODS: We searched Medline (via PubMed), China Biology Medicine, Chinese National Knowledge Infrastructure and WanFang databases and the websites of the main guideline development organizations from 2018 to 2020 for guidelines on gastric cancer. Data were extracted and the reporting quality evaluated by two researchers independently using the Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist. We assessed the compliance of the guidelines to each of the 35 items of RIGHT and summarized the reporting proportions of the seven domains of RIGHT. RESULTS: Eighteen guidelines were included. The mean proportion of appropriately reported RIGHT items was 52.4%. Among the seven domains of the RIGHT checklist, Basic information had the highest reporting rate (78.7%), and Review and quality assurance domain the lowest rate (16.7%). The domains Evidence (40.0%), Funding and declaration and management of interests (43.1%), and Other information (31.5%) had also reporting rates below 50%. Two RIGHT items (17 and 19b) were not reported by any of the guidelines. CONCLUSIONS: The reporting quality of gastric cancer guidelines published in the years 2018-2020 was suboptimal, especially regarding the reporting of review, quality assurance and evidence. Guideline developers should pay attention on rigorous reporting following international standard to improve the quality of guidelines.

Epidemiology, Diagnosis, Staging and Multimodal Therapy of Esophageal and Gastric Tumors.

Gastric and esophageal tumors are diverse neoplasms that involve mucosal and submucosal tissue layers and include squamous cell carcinomas, adenocarcinomas, spindle cell neoplasms, neuroendocrine tumors, marginal B cell lymphomas, along with less common tumors. The worldwide burden of esophageal and gastric malignancies is significant, with esophageal and gastric cancer representing the ninth and fifth most common cancers, respectively. The approach to diagnosis and staging of these lesions is multimodal and includes a combination of gastrointestinal endoscopy, endoscopic ultrasound, and cross-sectional imaging. Likewise, therapy is multidisciplinary and combines therapeutic endoscopy, surgery, radiotherapy, and systemic chemotherapeutic tools. Future directions for diagnosis of esophageal and gastric malignancies are evolving rapidly and will involve advances in endoscopic and endosonographic techniques including tethered capsules, optical coherence tomography, along with targeted cytologic and serological analyses.