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Background: Cancer patients at the end of life take numerous medications. However, it has not been assessed what proportion of patients take unnecessary medications and which patients are at risk for doing so.Methods: Cross-sectional survey of medications utilized by terminally ill ambulatory cancer patients, with the aim of identifying medications considered unnecessary as per explicit criteria. The criteria took into account whether drugs could benefit patients with terminal cancer.Results: Among 87 patients, 21 (24%, 95% confidence interval [CI] 15.6-34.5%) were taking at least one unnecessary medication, the most common being gastric protectors. In multivariable analyses, patients with Charlson Comobidity Index≤1 (OR: 4.49, CI95% 1.32-15.26; p=0.01) or whose medication list had not been reconciled by physicians (OR: 6.38, CI95% 1.21-33.40; p=0.02) were more likely to use an unnecessary medication.Conclusion: Patients with advanced cancer take many medications considered unnecessary. Medication reconciliation should be performed routinely for these patients. [ABSTRACT FROM AUTHOR]

Background: Cancer patients usually take many medications. The proportion of patients with advanced cancer who are taking futile drugs is unknown.Materials and Methods: We retrospectively reviewed the charts of all consecutive ambulatory patients with advanced cancer and who were receiving supportive care exclusively at palliative care clinics, Princess Margaret Hospital, to gather information on futile medications used by them. Futile medications were defined as unnecessary (when no short-term benefit to patients with respect to survival, quality of life, or symptom control was anticipated) or duplicate (two or more drugs from the same pharmacological class). Summary statistics were used to describe the results.Results: From November 2005 to July 2006, 82 (22%) of 372 patients were taking at least one futile medication before consultation; after initial consultation, this proportion dropped to 20% (78): 70 patients were taking unnecessary medications, while eight were on duplicate medications. The most frequent unnecessary medications used by patients were statins (56%). The most common duplicate medication involved the use of two different benzodiazepines (seven patients).Conclusion: About one fifth of cancer outpatients at the end of life take futile medications, most commonly statins. Prospective and population-based studies are warranted to further evaluate the magnitude and consequences of futile medication use in oncology. [ABSTRACT FROM AUTHOR]

CONTEXT: Although several studies have evaluated the frequency of adverse drug reactions (ADRs) and drug-drug interactions (DDIs) in general medicine, few studies have looked at the epidemiology of adverse drug events (ADEs) in oncology. OBJECTIVES: We sought to investigate how many hospital admissions in oncology are related to a DDI or an ADR. METHODS: All cancer patients admitted to an oncology ward during an eight-month period had their charts retrospectively evaluated for reasons of hospitalization, using a 4-point scale (definitely, probably, possibly, or unlikely associated) to classify admissions by their probability of being associated with either a DDI or an ADR. RESULTS: From September 2007 to May 2008, there were 550 hospital admissions and 458 were eligible. Among unplanned admissions (n=298), 39 (13.0%, 95% confidence interval [CI] 9.4%-17.4%) were considered to be associated with an ADE, 33 (11.0%, 95% CI 7.7%-15.2%) with an ADR, and six (2.0%, 95% CI 0.7%-4.3%) with a DDI. The most common DDIs involved warfarin, captopril, and anti-inflammatory agents, and the most frequent ADR was neutropenic fever post-chemotherapy. Most patients were discharged completely recovered, but two patients died. CONCLUSION: Approximately one in 10 unplanned hospitalizations of cancer patients is associated with an ADE. Prospective and population-based studies are warranted to evaluate their magnitude in oncology. [ABSTRACT FROM AUTHOR]

Background: Several tyrosine kinase receptors inhibitors (TKIs) have demonstrated antiproliferative effects in well-differentiated neuroendocrine tumors (NETs). We aimed to summarize and appraise the current evidence of the efficacy of TKIs in patients with different types of NETs., Methods: We performed a systematic review of clinical trials of TKIs in patients with advanced gastroenteropancreatic or lung NETs (PROSPERO registration number: CRD42024507379). Population characteristics, efficacy, and safety results were summarized by type of NET., Results: Twenty-eight studies were eligible, totaling 2284 patients. While sunitinib remains the only Food and Drug Administration-approved TKI in patients with NETs (for patients with pancreatic well-differentiated NETs), recent placebo-controlled randomized trials have demonstrated improved response rates and progression-free survival for patients with progressive and pre-treated well-differentiated pancreatic (cabozantinib or surufatinib) or gastrointestinal (GI) NETs (pazopanib, cabozantinib, or surufatinib). There is limited evidence to support the use of a TKI in patients with lung or grade 3 NETs. The toxicity associated with TKIs follows a class effect, with a significant proportion of patients experiencing fatigue, hypertension, and hand-foot skin reactions., Conclusion: TKIs are effective therapies in patients with pancreatic or GI well-differentiated NETs and should be part of the therapeutical sequencing of these patients., Competing Interests: R.G.T.: honoraria for lectures from Ipsen. F.P.C.: none to declare. J.F.R.: honoraria for lectures from Ipsen and Novartis. R.P.R.: honoraria for lectures and advisory board from Ipsen., (© The Author(s), 2024.)

Neuroendocrine neoplasms are a diverse group of neoplasms that can occur in various areas throughout the body. Well-differentiated neuroendocrine tumors (NETs) most often arise in the gastrointestinal tract, termed gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Although GEP-NETs are still uncommon, their incidence and prevalence have been steadily increasing over the past decades. The primary treatment for GEP-NETs is surgery, which offers the best chance for a cure. However, because GEP-NETs are often slow-growing and do not cause symptoms until they have spread widely, curative surgery is not always an option. Significant advances have been made in systemic and locoregional treatment options in recent years, including peptide-receptor radionuclide therapy with α and β emitters, somatostatin analogs, chemotherapy, and targeted molecular therapies., (© 2024 American Cancer Society.)

Gastric neuroendocrine neoplasms (gNENs) display peculiar site-specific features among all NENs. Their incidence and prevalence have been rising in the past few decades. gNENs comprise gastric neuroendocrine carcinomas (gNECs) and gastric neuroendocrine tumours (gNETs), the latter further classified into three types. Type I anatype II gNETs are gastrin-dependent and develop in chronic atrophic gastritis and as part of Zollinger-Ellison syndrome within a multiple endocrine neoplasia type 1 syndrome (MEN1), respectively. Type III or sporadic gNETs develop in the absence of hypergastrinaemia and in the context of a near-normal or inflamed gastric mucosa. gNECs can also develop in the context of variable atrophic, relatively normal or inflamed gastric mucosa. Each gNEN type has different clinical characteristics and requires a different multidisciplinary approach in expert dedicated centres. Type I gNETs are managed mainly by endoscopy or surgery, whereas the treatment of type II gNETs largely depends on the management of the concomitant MEN1. Type III gNETs may require both locoregional approaches and systemic treatments; NECs are often metastatic and therefore require systemic treatment. Specific data regarding the systemic treatment of gNENs are lacking and are derived from the treatment of intestinal NETs and NECs. An enhanced understanding of molecular and clinical pathophysiology is needed to improve the management and outcomes of patients' gNETs., (© 2024. Springer Nature Limited.)

Lack of expression of the tumour suppressor gene caudal-type homeobox 2 ( CDX2 ) associates with poor outcomes in early stage colorectal cancer (CRC). Yet its prognostic value in the context of other prognostic biomarkers in metastatic CRC (mCRC) is unknown. Overexpressed cyclooxygenase-2 (COX2) has been reported in advanced CRC. However, CDX2 and COX2 relationship in mCRC remains undetermined. We aimed to assess their expression in mCRC tumours from a clinically characterised cohort and their influence on overall survival (OS) and progression-free survival (PFS) in first line. Among 720 consecutive mCRC patients, 346 had tumour samples appropriate for tissue microarray assembly and immunohistochemistry analyses. Clinical and survival data were retrospectively assessed. Loss of CDX2 expression was detected in 27 (7.8%) samples, enriched in poorly differentiated tumours (20%; p < 0.01) and in those with the BRAF p.V600E variant (40%; p < 0.01). Most tumours (93.4%) expressed COX2. COX2-negative samples were enriched in poorly differentiated mCRC. In unadjusted analyses, median OS ( p < 0.001) and median PFS ( p < 0.05) were inferior for patients with CDX2-negative versus CDX2-positive tumours. In conclusion, loss of CDX2 was significantly associated with poorly differentiated mCRC and BRAF p. V600E allele and a prognostic marker of worse OS., Competing Interests: The authors declare that they have no conflicts of interest to disclose regarding the publication of this manuscript., (© the authors; licensee ecancermedicalscience.)

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., (© 2023 Wiley Periodicals LLC.)

Introduction: Colorectal cancer is the second most common cancer in both genders and often presents as a metastatic, unresectable, or recurrent disease in early follow-up. It is uncertain the benefit of oxaliplatin-based palliative chemotherapy (CT) in the first line of treatment in patients with compromised performance status (PS), Eastern Cooperative Oncology Group (ECOG) 3 and 4. These patients are systematically excluded from clinical trials but may be treated in clinical practice., Methods: We conducted a prospective observational cohort whose primary outcome was improving at least 2 points in the worst symptom in the Edmonton Symptom Assessment System Scale (ESAS-r), without grade 3 to 4 toxicity, comparing baseline and fourth week of treatment. Secondary endpoints included quality of life using the European Quality of Life-5 dimensions questionnaire, toxicity, response rate, clinical improvement of ECOG PS, and overall survival (OS)., Results: We included 28 patients, and 12 (42.8%) achieved the primary endpoint. Median overall survival was 86 days, 46% of patients did not respond to the fourth-week reevaluation due to clinical deterioration, and 17.8% presented toxicity grade ≥3, with 5 patients dying from toxicity. In addition, ECOG PS 4 or cholestasis had poorer overall survival. Finally, 25% and 53.6% of patients received these treatments in the last 14 and 30 days of life, respectively., Conclusion: In the present study, palliative multiagent chemotherapy in poor performance status patients with non-molecularly selected colorectal cancer tended to impact tumor symptoms control; however, there is no benefit in OS and a considerable risk of toxicity and treatment-related death., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The standard neoadjuvant therapy for rectal cancer involves fluoropyrimidines and radiotherapy and, most recently, total neoadjuvant therapy (TNT). A drug-drug interaction between fluoropyrimidines and proton-pump inhibitors (PPI) was suggested, with a negative impact on oncological outcomes in breast, colon and gastric cancers. Little is known about such an effect on rectal tumours. We aimed to evaluate the impact of PPI utilisation on the pathological response after chemoradiation for rectal cancer., Materials and Methods: Retrospective multicentre study of rectal cancer patients treated with neoadjuvant chemoradiotherapy with capecitabine (cohort 1) or 5-fluororuracil (5-FU) (cohort 2); TNT with oxaliplatin-based regimens was allowed. The pathological response was considered a complete (ypCR) or complete + partial (ypCR + ypPR) according to American Joint Committee on Cancer. PPI use was considered at any time during the neoadjuvant period if concomitant to fluoropyrimidines., Results: From January 2007 to November 2020, 251 patients received capecitabine and 196 5-FU. The rates of PPI use in cohorts 1 and 2 were 20.3% and 26.5%, respectively. TNT was offered to 18.3% in cohort 1. PPI use did not influence ypCR in cohort 1 (yes versus no: 29.4% versus 19.5%; p = 0.13) or 2 (yes versus no: 25.0% versus 26.4%; p = 1.0). Similar ypCR + ypPR were observed in both cohorts 1 (76.5% versus 72.0%; p = 0.60) and 2 (86.5% versus 76.4%; p = 0.16). PPI use was not associated with pathological response in multivariable analysis. PPI users experienced more grade 3 or higher diarrhoea and infections., Conclusion: PPI concomitant to capecitabine/5-FU chemoradiation did not influence the pathological response in rectal cancer but was associated with more treatment-related adverse events., Competing Interests: No conflicts of interest to declare., (© the authors; licensee ecancermedicalscience.)

Background: Nearly 30% of neuroendocrine tumors (NETs) have evidence of immunohistochemical (IHC) expression of estrogen (ER) and/or progesterone (PR) receptors. Therefore, targeting ER/PR may offer an effective NET-directed treatment to select patients., Methods: We conducted a multicenter Simon two-stage single-arm phase II trial of tamoxifen in patients with metastatic, progressive NETs. Eligible patients had positive IHC expression of ER and/or PR ⩾ 1%. Prior therapy with somatostatin analogs was required for progressing/functioning cases. Main exclusion criterion was aggressive disease requiring cytotoxic therapy. The primary end point was disease control rate (DCR) at week 24 by Response Evaluation Criteria in Solid Tumors version 1.1. We planned to enroll 23 patients in the first stage, to reach a DCR at week 24 of 70% ( versus 50%); if ⩾12 patients reached the primary end point, a total of 37 would be included., Results: From February 2019 to February 2022, 23 out of 59 patients were eligible and enrolled: 15 (65%) were females; the most common sites were pancreas (11; 48%) and small bowel (6; 26%). In all, 13 patients (56.5%) had G2 NETs. At a median follow-up of 27 months, 13 patients (56.5%) had stable disease at week 24 and median progression-free survival (PFS) was 7.9 months [interquartile range (IQR): 3.7-12.1]. The best response was stable disease in 13 patients, with most patients experiencing minor tumor growth. Median PFS times were not significantly different according to ER/PR < or ⩾30% ( p  = 0.49) or ER versus PR expression ( p  = 0.19). One patient experienced grade 2 constipation., Conclusion: Tamoxifen for ER-/PR-positive NETs patients is safe but offers modest antitumor effects., Trial Registry Name: Study of Tamoxifen in Well Differentiated Neuroendocrine Tumors and Hormone Receptor Positive Expression (HORMONET)., Url: https://clinicaltrials.gov/ct2/show/NCT03870399?term=03870399&draw=2&rank=1., Registration Number: NCT03870399., Competing Interests: MJB: none; JS: Honoraria from Ipsen and Tersera; TAT: none; LD: none; MDD: honoraria from Novartis and Ipsen; CAM: none; VHFJ: none; TCF: none; RGT: none; RPR: honoraria from Novartis and Ipsen., (© The Author(s), 2023.)

Neuroendocrine neoplasms (NENs) are a rare group of cancers with heterogeneous behaviour and mostly of unknown aetiology. Excluding some infrequent hereditary cancer syndromes, the extent and clinical significance of mutations in other cancer predisposing genes (CPGs) are not known. We aimed to investigate the frequency of pathogenic and likely germline pathogenic variants (GPVs) in known CPGs in young adults with NEN and the clinical and molecular characteristics of these patients. We recruited 108 patients with lung or digestive NEN diagnosed between 18 and 50 years and performed targeted sequencing of 113 CPGs on germline DNA. For some patients, tumour features such as loss of heterozygosity (LOH), tumour mutation burden and microsatellite instability were evaluated. GPVs were detected in 17 patients (15.7%). Median age, sex, stage at diagnosis, family history of NENs or any personal history of neoplasm were similar between patients with or without GPVs. GPV carriers had more gastric (P = 0.084), functioning NEN (P = 0.041), positive family history of cancer (P = 0.015) and exclusively well-differentiated histology. Genes affected were mostly involved in DNA repair (CHEK2, ERCC2, ERCC3, XPC, MSH6, POLE and SLX4), with most GPVs found in MUTYH (four cases). LOH was performed in eight tumours and detected only in an SLX4-positive case. Overall, our findings indicate a role of inherited genetic alterations, particularly in DNA repair genes, in NEN carcinogenesis in young adults. These patients more often had a family history of cancer and functioning NENs.

Neuroendocrine neoplasms (NENs) comprise a beautifully complicated, exciting landscape of histologies and clinical behaviors. However, the nuanced complexity of low- and high-grade variants can easily overwhelm both patients and providers. In this chapter, we review the ever-expanding literature on both functioning and nonfunctioning small bowel and pancreatic NENs, touching on somatostatin analogs, hepatic-directed therapies, small molecules, radiopharmaceuticals, immunotherapy, cytotoxic chemotherapy, and new promising agents. Furthermore, we suggest some strategies to address the most challenging scenarios seen in clinical practice, including sequencing of agents, treatment of carcinoid syndrome, and options for well-differentiated high-grade disease.

Background: Anal canal squamous cell carcinoma (SCC) is a relatively uncommon neoplasia, and it is mostly a local-regional cancer, of low metastatic potential (only 15%), resulting in cure in most cases treated with definitive chemoradiation. On the other hand, its incidence has been steadily increasing over the last decades, which makes it an important public health problem. In an effort to provide surgeons and oncologists who treat patients with anal cancer with the most updated information based on the best scientific evidence, the Brazilian Society of Surgical Oncology (SBCO) has produced the present guideline for the management of anal canal SCC, focused on the main topics related to daily clinical practice., Objectives: The SBCO developed the present guidelines to provide recommendations on the main topics related to the management of anal canal squamous cell carcinoma (SCC) based on current scientific evidence., Methods: Between October 2022 and January 2023, 14 experts met to develop the guidelines for the management of anal canal cancer. A total of 30 relevant topics were distributed among the participants. The methodological quality of a final list with 121 sources was evaluated, all the evidence was examined and revised, and the management guidelines were formulated by the 14-expert committee. To reach a final consensus, all the topics were reviewed in a meeting that was attended by all the experts., Results: The proposed guidelines contained 30 topics considered to be highly relevant in the management of anal canal cancer, covering subjects related to screening recommendations, preventive measures, tests required for diagnosing and staging, treatment strategies, response assessment after chemoradiotherapy, surgical technique-related aspects, and follow-up recommendations. In addition, screening and response assessment algorithms, and a checklist were proposed to summarize the important information and offer an updated tool to assist surgeons and oncologists who treat anal canal cancer and in providing the best care to their patients., Conclusion: These guidelines summarize recommendations based on the most current scientific evidence on relevant aspects of anal canal cancer management and are a practical guide to help surgeons and oncologists who treat anal canal cancer make the best therapeutic decisions., (© 2023 Wiley Periodicals LLC.)

Purpose: The European Organisation for Research and Treatment of Cancer (EORTC) health-related quality of life questionnaire for anal cancer (QLQ-ANL27) supplements the EORTC cancer generic measure (QLQ-C30) to measure concerns specific to people with anal cancer treated with chemoradiotherapy. This study tested the psychometric properties and acceptability of the QLQ-ANL27., Methods and Materials: People with anal cancer were recruited from 15 countries to complete the QLQ-C30 and QLQ-ANL27 and provide feedback on the QLQ-ANL27. Item responses, scale structure (multitrait scaling, factor analysis), reliability (internal consistency and reproducibility) and sensitivity (known group comparisons and responsiveness to change) of the QLQ-ANL27 were evaluated., Results: Data from 382 people were included in the analyses. The EORTC QLQ-ANL27 was acceptable, comprehensive, and easy to complete, taking an average 8 minutes to complete. Psychometric analyses supported the EORTC QLQ-ANL27 items and reliability (Cronbach's α ranging from 0.71-0.93 and test-retest coefficients above 0.7) and validity of the scales (particularly nonstoma bowel symptoms and pain/discomfort). Most scales distinguished people according to treatment phase and performance status. Bowel (nonstoma), pain/discomfort, and vaginal symptoms were sensitive to deteriorations over time. The stoma-related scales remained untested because of low numbers of people with a stoma. Revisions to the scoring and question ordering of the sexual items were proposed., Conclusions: The QLQ-ANL27 has good psychometric properties and is available in 16 languages for people treated with chemoradiotherapy for anal cancer. It is used in clinical trials and has a potential role in clinical practice., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Prognostic and predictive markers in metastatic pheochromocytoma and paraganglioma (mPPGL) are unknown. We aimed to evaluate epidemiology of mPPGL, and prognostic factors of overall survival (OS) and predictive markers of treatment duration with first-line chemotherapy (TD1L)., Patients and Methods: Retrospective multicentre study of adult patients with mPPGL treated in Latin American centres between 1982 and 2021., Results: Fifty-eight patients were included: 53.4% were female, median age at diagnosis of mPPGL was 36 years and 12.1% had a family history of PPGL. The primary site was adrenal, non-adrenal infradiaphragmatic and supradiaphragmatic in 37.9%, 34.5% and 27.6%, respectively. 65.5% had a functioning tumour and 62.1% had metachronous metastases. Positive uptakes were found in 32 (55.2%) 68 Gallium positron emission tomography (PET/CT), 27 (46.6%) 2-deoxy-2-[fluorine-18]fluoro-D-glucose PET/CT and 37 (63.8%) of 131 Iodine-metaiodobenzylguanidine (MIBG) tests. Twenty-three (40%) patients received first-line chemotherapy, with cyclophosphamide, vincristine and dacarbazine used in 12 (52%) of patients. At a median follow-up of 62.8 months, median TD1L was 12.8 months. Either functional exams, tumour functionality, pathological characteristics or primary tumour location were significantly associated with response or survival. Yet, negative MIBG, Ki67 ≥ 10%, infradiaphragmatic location and functional tumours were associated with numerically inferior OS., Conclusions: In patients with mPPGL, prognostic and predictive factors to chemotherapy are still unknown, but negative MIBG uptake, Ki67 ≥ 10%, infradiaphragmatic location and functional tumours were numerically linked to worse OS. Our results should be further validated in larger and independent cohorts., Competing Interests: No conflicts of interest to declare., (© the authors; licensee ecancermedicalscience.)

Background: Gastroenteropancreatic (GEP) neuroendocrine neoplasms with Ki-67 > 20% were subdivided in the most recent 2019 World Health Organization histopathological classification into grade 3 (G3) neuroendocrine tumors (NETs), described as well-differentiated tumors, and neuroendocrine carcinomas, which are described as poorly differentiated tumors. This classification met the demand noted for different prognoses between these subgroups, prompting the need for treatment recommendations for well-differentiated G3 tumors., Methods: We systematically searched medical literature databases and oncology conferences for studies on G3 GEP NET to describe epidemiology, diagnosis, molecular features, and treatments used. We excluded studies that did not discriminate G3 NET data. Data were tabulated and described, and a quality analysis of the reports was performed., Results: We found 23 published studies and six abstracts; 89.7% of studies were retrospective, six were composed exclusively of G3 NETs. Among 761 patients, the median number of patients per study was 15, most were male and older than 60 years, and functional imaging tests were positive in more than 80% of cases. Overall, the scientific evidence supporting the treatment of G3 GEP NETs is limited. For localized disease, resection remains the standard treatment but there is no evidence to support neoadjuvant or adjuvant therapy. For advanced disease, capecitabine and temozolomide seems to be the most effective option, with a response rate, median progression-free survival, and median overall survival up to 37.9%, 20.6 months, and 41.2 months, respectively., Conclusion: The latest available data on the epidemiology, diagnosis, molecular changes, and treatment of G3 GEP NET are described. Yet, the level of evidence for treatment recommendations is low, as most studies are retrospective. A treatment algorithm for G3 GEP NET is proposed., Competing Interests: Rachel P. Riechelmann: honoraria for lectures from Novartis and Ipsen; Mauro D. Donadio: honoraria for lectures from Novartis and Ipsen. Ângelo B. Brito: nothing to declare., (© The Author(s), 2023.)

Localized anal cancer is mostly represented by squamous cell carcinoma of the anus (SCCA) and is cured in ≥80 % of cases by chemoradiation (CRT). Development of techniques for detection/evaluating circulating tumor cells (CTCs) for diagnosis/ prognosis/response to therapy can change the manner we treat/follow SCCA patients., Objective: to detect CTCs from patients with SCCA and evaluate the presence of HPV virus, p16 expression and markers related to resistance to CRT (RAD23B/ ERCC1/ TYMS) in CTCs at baseline and after CRT., Methods: CTCs were isolated/quantified by ISET®, protein expressions were analyzed by immunocytochemistry and HPV DNA was detected by chromogenic in situ hybridization., Results: We enrolled 15 patients: median age was 61 (43-73) years, the majority was women (10/15). CTCs were detected in all patients at baseline (median= 0.4 (0.4-3.33) CTCs/mL) and in 8/9 patients, after CRT (median= 2.33 (0-7.0) CTCs/mL). DNA from HPV was found in CTCs in 14/15 patients (93.33 %) at baseline and in 7/9 (77.7 %) after treatment. At a median follow-up of 22.20 (1.45-38.55) months, three patients expressed ERCC1 in CTCs after treatment, with one of them having disease recurrence., Conclusion: We showed that detection of HPV in CTCs from patients with non-metastatic SCCA is feasible and appears to be a sensitive diagnostic method. These results may be clinically useful for better monitoring these patients. However, future larger cohorts may demonstrate whether there is any correlation between the presence of HPV and the expression of screening markers for CRT in SCCA., Competing Interests: Conflicts of interest All authors declared that there are no conflicts of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

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.

Introduction: The role of primary prophylaxis (PP) with granulocyte colony-stimulating factor (G-CSF) for patients with metastatic pancreatic adenocarcinoma (MPA) treated with FOLFIRINOX is unknown. We aimed to compare the frequencies of grades 3 or 4 neutropenia (G3/4N) and febrile neutropenia (FN) and survival outcomes according to the use of PP., Methods: This is a retrospective study. We included patients with pathologically confirmed MPA treated with FOLFIRINOX in first-line. Patients who received primary prophylaxis (PP group) were compared to patients who received secondary or no G-CSF (no-PP group). Overall survival (OS) and progression-free survival (PFS) were evaluated using the standard Cox proportional hazard model. To account for potential biases, we performed sensitivity analyses excluding patients who received secondary prophilaxis and treating G-CSF as a time-dependent covariate in extended Cox proportional hazard models., Results: The study population consisted of 123 patients. PP was used by 75 patients (61.0%). G3/4 N occurred more frequently among patients without PP (10.7 vs 41.7%; P < .001). There was no difference in the frequency of FN between groups (5.3 vs 8.3%; P = .710). In multivariate analysis, PP was associated with a trend toward improved OS (HR = .66; 95% confidence interval [95% CI] .41 - 1.07; P = .094). In the multivariate model excluding patients with secondary prophylaxis (HR = .54; 95% CI 0.32 - .91; P = .022) and in the time-dependent model (HR = .47; 95% CI 0.28 - .80; P = .005), PP was associated with statistically superior OS., Conclusions: Despite the reduction in the frequency of G3/4N, the risk of FN among patients treated with FOLFIRINOX without G-CSF is too low to justify its use in a routine basis. However, given the potential of G-CSF to improve survival in this setting, further studies are warranted to assess its role during treatment with FOLFIRINOX for patients with MPA.

Background: Patients with T2N0 squamous cell carcinoma of the anal canal (SCCA) have comprised less than 30% of patients enrolled in phase III clinical trials of curative-intent definitive chemoradiation. We aimed to evaluate treatment outcomes of these patients according to dose-intensity of chemoradiation., Materials and Methods: Retrospective multicenter study of patients with T2N0 SCCA, with the primary endpoint to compare the progression-free survival (PFS) of patients treated with full definitive chemoradiotherapy (f-CRT, CRT with 2 drugs) versus a nonstandard treatment (NST; radiotherapy only or CRT with 1 drug). Secondary outcomes were rates of complete response (CR), salvage surgery, and colostomy. PFS time was analyzed using the Kaplan-Meier method and differences in survival outcomes were assessed using the log-rank test and adjusted for prognostic covariates using a multivariable Cox regression model RESULTS: From March 2006 to January 2020, 74 patients were included. Most patients (n = 58; 78.4%) received f-CRT. In a median follow up time of 66.1 months, the unadjusted median PFS was 128.3 months (95% confidence interval [CI] 105.5-151.1) for f-CRT versus 74.1 months for NST (95% CI 45.8-102.4; P = .067). CR was achieved by 51 (87.9%) versus 11 (68.9%; P = .065) patients treated with f-CRT or an NST, respectively. Comparing f-CRT versus NST, the colostomy rates were higher for those treated with an NST: 5 (32.8%) versus 5 (9.5%; P = .019) CONCLUSION: For patients with T2N0 SCCA, f-CRT remains the standard treatment, offering higher CR and less likelihood of colostomy., (Copyright © 2022. Published by Elsevier Inc.)

Immunotherapy can be considered a therapeutic revolution in oncology, with great impact on many tumor types, such as melanoma and non-small cell lung cancer. However, in metastatic colorectal cancer, the benefits in terms of prolonged tumor control and high response rate are limited to the rare subgroup of tumors with high mutation burden - mostly tumors that harbor microsatellite instability (MSI) or a deficient mismatch repair system (dMMR), or tumor microsatellite stability and damaging mutations in the exonuclease domains of POLE or POLD. The KEYNOTE-028 uncontrolled phase II trial demonstrated an impressive antitumor activity of pembrolizumab in patients with treatmentrefractory Lynch-associated tumors, including colorectal cancer. Nivolumab with or without ipilimumab confirmed the efficacy of immune checkpoint inhibitors in patients with previously treated dMMR / MSI metastatic colorectal cancer. The recent KEYNOTE-177 phase III trial demonstrated that pembrolizumab significantly reduced the relative risk of disease progression or death and improved progression-free survival in patients with treatment-naive dMMR / MSI metastatic colorectal cancer in comparison with first-line chemotherapy with or without biologics. Unfortunately, current pharmacological strategies with immunotherapy have not been successful for most patients with microsatellite stable metastatic colorectal cancer. In this review, we critically appraise the applicability of immune checkpoint inhibitors in dMMR/MSI metastatic colorectal cancer. We also discuss the recent negative trials of immunotherapy combinations in microsatellite stabl., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Objectives: The incidence, predictive, and prognostic impact of programmed cell death (PD-L1) expression in gastric (GC) and gastroesophageal junction tumors (GEJC) treated with perioperative chemotherapy is poorly understood. We aimed to assess PD-L1 expression by immunohistochemistry (IHC) in both pre and posttreatment specimens evaluating its impact on pathological response and survival outcomes., Methods: Retrospective cohort of patients with GC and GEJ tumors treated in a single western cancer center between 2007 and 2017. PD-L1 expression was assessed by IHC before and after neoadjuvant chemotherapy, in surgical samples, and reported as combined positive score (CPS). CPS > 1% was tested for its association with pathological response and overall survival (OS)., Results: We were able to assess PD-L1 expression in at least one tissue sample from 155 subjects. PD-L1 positivity rate was 20%. In 74 paired samples, a 21% discordance between PD-L1 expression in biopsy sample and surgical specimen was observed. With a median follow-up period of 60.3 months, 5-years disease-free survival was 60.5% with a median OS not reached. PD-L1 expression was neither associated with pathological response or survival outcomes., Conclusions: PD-L1 expression in the setting of locally advanced GC tumors was relatively low and can vary considering the tissue sample analyzed. This expression had no association with survival or pathological response in this population., (© 2022 Wiley Periodicals LLC.)

The 2019 Word Health Organization (WHO) subclassified grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) into neuroendocrine carcinoma (NEC) or tumours (G3 NET) based on morphology and proliferation. Yet, few data exist on molecular profiles for G3 NEN. We compared clinicopathological and molecular characteristics of these two groups. We retrospectively reviewed consecutive G3 GEP NEN patients and had their tumour tissues reviewed, reclassified as per the WHO 2019, and analyzed by a next-generation sequencing (NGS) panel. Between 2000 and 2019, 43 patients had pathology revision: 29 (67%) were NEC and 14 (33%) were G3 NET, with a 23% change in diagnosis. Median overal survival for G3 NET and NEC patients was 55.6 and 11.9 months, respectively (hazard ratio = 2.78 [95% confidence interval = 1.09-7.11], p = .042), which was confirmed by an adjusted analysis (hazard ratio = 2.90 NEC vs. G3 NET; p = .03). NGS was performed in 32 cases: 21 NEC and 11 G3 NET. Mutations in RB1 and PTEN were exclusively encountered in NEC. Median tumour mutational burden was 5 (0-67) mutations per megabase in NEC and 4.5 (0-9) among G3 NET. Microsatellite instability was found in 3 (14.3%) NEC cases. In conclusion, pathology revision is essential to estimate prognosis and therapeutic plan. G3 GEP NEN generally harbour low tumor mutation burden and fewer actionable mutations, but 14% of NEC cases were microsatellite unstable and could benefit from immune checkpoint inhibitors., (© 2022 British Society for Neuroendocrinology.)

The clinical and pathological responses to multimodal neoadjuvant therapy in locally advanced rectal cancers (LARCs) remain unpredictable, and robust biomarkers are still lacking. Recent studies have shown that tumors present somatic molecular alterations related to better treatment response, and it is also clear that tumor-associated bacteria are modulators of chemotherapy and immunotherapy efficacy, therefore having implications for long-term survivorship and a good potential as the biomarkers of outcome. Here, we performed whole exome sequencing and 16S ribosomal RNA (rRNA) amplicon sequencing from 44 pre-treatment LARC biopsies from Argentinian and Brazilian patients, treated with neoadjuvant chemoradiotherapy or total neoadjuvant treatment, searching for predictive biomarkers of response (responders, n = 17; non-responders, n = 27). In general, the somatic landscape of LARC was not capable to predict a response; however, a significant enrichment in mutational signature SBS5 was observed in non-responders ( p = 0.0021), as well as the co-occurrence of APC and FAT4 mutations ( p < 0.05). Microbiota studies revealed a similar alpha and beta diversity of bacteria between response groups. Yet, the linear discriminant analysis (LDA) of effect size indicated an enrichment of Hungatella, Flavonifractor , and Methanosphaera (LDA score ≥3) in the pre-treatment biopsies of responders, while non-responders had a higher abundance of Enhydrobacter, Paraprevotella (LDA score ≥3) and Finegoldia (LDA score ≥4). Altogether, the evaluation of these biomarkers in pre-treatment biopsies could eventually predict a neoadjuvant treatment response, while in post-treatment samples, it could help in guiding non-operative treatment strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Takenaka, Bartelli, Defelicibus, Sendoya, Golubicki, Robbio, Serpa, Branco, Santos, Claro, dos Santos, Kupper, da Silva, Llera, de Mello, Riechelmann, Dias-Neto, Iseas, Aguiar and Nunes.)

Background: Everolimus-induced pneumonitis (EiP) has been poorly studied in patients with neuroendocrine neoplasms (NEN) outside clinical trials. The aim of this study was to evaluate the incidence, risk factors, and outcomes of EiP in patients with NENs using real-world data., Methods: Retrospective study of everolimus-treated patients with advanced NENs. Imaging reports were systematically reviewed for the presence of pneumonitis. Clinical features and treatment profiles for EiP were summarized. Overall survival (OS) was calculated from the initiation of everolimus to the date of death or last follow-up using the Kaplan-Meier method., Results: A total of 122 patients were included. Median age at start of everolimus was 62 (19-86) years, 62% (76/122) were male, and half were from pancreatic origin (62, 51%). Twenty-eight patients (23%) developed EiP: 82% grade (G)1 or G2, 14% G3 and 4% G4. The median time to EiP was 3.6 (0.8-51) months. Primary tumor site, concurrent lung disease, smoking history, and prior therapies were not associated with the onset of EiP. Patients who developed EiP had longer time on everolimus treatment (median 18 months vs 6 months; P = .0018) and OS (77 months vs 52 months; P = .093). Everolimus-induced pneumonitis was a predictor of improved OS by multivariable analysis (HR 0.39, 95% CI 0.19-0.82; P = .013)., Conclusion: Everolimus-induced pneumonitis in the real-world clinical setting is present in one quarter of patients with NENs receiving everolimus and often occurs early. While risk factors for EiP were not identified, patients with EiP had improved survival., (© The Author(s) 2022. Published by Oxford University Press.)

Background: HIV-positive patients are underrepresented in clinical trials of metastatic squamous cell carcinoma of the anal canal (mSCCA). We aimed to compare the clinical outcomes of mSCCA patients according to HIV infection., Methods: This was a retrospective multicenter cohort study of consecutive patients with mSCCA. All HIV-positive patients received antiretroviral therapy. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS) and response rate (RR)., Results: From January 2005 to December 2019, 113 patients were included: 20 (17.6%) had HIV infection. HIV-positive patients were younger at diagnosis and more frequently male, and 20% (n = 8) received exclusively best supportive care in comparison with 8.6% of HIV-negative patients (P = .13). Both groups were similar in terms of Eastern Cooperative Oncology Group (ECOG) performance status, pattern of metastatic disease, and type of first-line chemotherapy. Five (25%) HIV-positive and 36 (38.7%) HIV-negative patients received second-line therapies (P = .24). RR and median PFS in first-line were similar between the groups: 35% and 30.1% (P = .78) and 4.9 and 5.3 months (P = .85) for patients with and without HIV infection, respectively. At a median follow-up of 26 months, median OS was 11.3 months (95% confidence interval [CI] 10.1 to 26.4) for HIV-infected patients versus 14.6 months (95% CI 11.1 to 18.1) for HIV-negative patients (P = .92). In the univariate analysis for OS, only ECOG performance status was significant., Conclusion: HIV-positive mSCCA patients under antiretroviral therapy have oncological outcomes similar to those of HIV-negative patients. These patients should be included in trials of mSCCA., Competing Interests: Declaration of Competing Interest None to declare, (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Although Chemoradiation (CRT) is the curative treatment for SCCAC, many patients present primary resistance. Since it is a rare tumor, response predictors remain unknown. Methods: We performed a prospective cohort study to evaluate biomarkers associated with CRT response, progression-free survival (PFS), and overall survival (OS). The primary endpoint was response at 6 months (m). Tumor DNA and HPV were analyzed by next-generation sequencing, while KI-67 and PD-L1 by immunohistochemistry in tumor tissue. Results: Seventy-eight patients were recruited between October/2011 and December/2015, and 75 were response evaluable. The median age was 57 years, 65% (n=49) were stage III and 12% (n=9) were HIV positive (HIV+). At 6m, 62.7% (n=47) presented CR. On multivariate analyses, stage II patients were 4.7 more likely to achieve response than stage III (OR, 4.70; 95%CI, 1.36-16.30; p=0.015). HIV+ was associated with a worse response (OR, 5.72; 95%CI, 2.5-13.0; p<0.001). 5-year PFS and OS rates were 63.3% and 76.4%, respectively, with a median follow up of 66m. On multivariate analyses, older age (HR 1.06, p=0.022, 95%IC 1.01-1.11) and absence of CR at 6m (HR 3.36, p=0.007, 95%IC 1.39-8.09) were associated with inferior OS. The 5-year OS rate was 62.5% in HIV+ group compared to 78% among HIV- pts, although this difference was not statistically significant (p=0.4). PIK3CA, MET and TP53 mutations, HPV, Ki-67 expression, and PD-L1 expression, were not associated with PFS and OS. Conclusions: Clinical stage III and HIV+ were associated with worse response to CRT at 6m. The absence of CR was the main factor associated with poor 5-year OS., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

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., Competing Interests: Victor Hugo Fonseca de Jesus received honoraria from United Medical and had travel expenses paid by United Medical in the past 12 months. United Medical is the company responsible for the distribution and sale of nab-paclitaxel in Brazil. Rachel Pimenta Riechelmann received consultancy fees from Astra Zeneca in the past 12 months., (© the authors; licensee ecancermedicalscience.)

Purpose: The utility of administering fluorouracil (5-FU) in bolus in regimens of infusional 5-FU has been questioned. We aimed to quantify the use of 5-FU bolus in infusional regimens for gastrointestinal malignancies among Brazilian oncologists., Methods: This was a cross-sectional electronic survey composed of eight multiple-choice questions sent to Brazilian oncologists during 14 days in February 2021. The survey instrument collected demographic data of participants and assessed practices in terms of 5-FU bolus use. We evaluated the association of demographic variables and 5-FU prescribing patterns with Fisher's exact test (odds ratio [OR])., Results: The survey was completed by 332 medical oncologists. Overall, 37% were experienced oncologists and 32% were gastrointestinal specialists. In the first-line metastatic and in the adjuvant settings, 40% and 67% of oncologists always prescribe 5-FU bolus in infusional regimens, respectively. Experienced oncologists more frequently omit 5-FU bolus when compared with early-career oncologists, both in the metastatic (41% v 26%; OR, 1.98; P = .005) and adjuvant settings (28% v 14%; OR, 2.32; P = .003). In addition, more GI specialists remove 5-FU bolus when compared with generalists, but only in the metastatic setting (44% v 25%; OR, 2.33; P = .001). GI specialists are more likely to consider that treatment efficacy is not affected by 5-FU bolus withdrawal than are generalists (89% v 75%; OR, 2.65; P = .003). Most respondents (67%) keep leucovorin at the same doses when omitting 5-FU bolus, and only 16% always recommend dihydropyrimidine dehydrogenase testing., Conclusion: Our survey indicates that experience in oncology practice and percentage of time dedicated to treat GI cancers influence the prescription of 5-FU bolus in Brazil, with more frequent omission of it among experienced gastrointestinal specialists, particularly in the metastatic setting., Competing Interests: Anelisa K. CoutinhoConsulting or Advisory Role: Amgen, Bayer, Roche/Genentech, Merck Serono, MSD Oncology, Sanofi/Aventis, Servier, United MedicalSpeakers' Bureau: Amgen, Bayer, Lilly, Roche/Genentech, Merck Serono, MSD Oncology, Roche Molecular Diagnostics, Sanofi/Aventis, Novartis, Servier, United Medical, Johnson & Johnson/Janssen, AstraZenecaResearch Funding: Bristol Myers Squibb, Servier Rui Fernando WeschenfelderHonoraria: Bayer, Lilly, MSD, Ipsen, NovartisConsulting or Advisory Role: Bayer, Lilly, MSD, Novartis, Ipsen Duilio RochaConsulting or Advisory Role: NovartisSpeakers' Bureau: Novartis, Ipsen, Bayer, Merck Serono, United Medical, Servier Aline Chaves AndradeSpeakers' Bureau: Bayer Gustavo dos Santos FernandesHonoraria: Roche, MSD Oncology, BayerResearch Funding: Roche, Memorial Sloan-Kettering Cancer Center, BMS BrazilTravel, Accommodations, Expenses: Roche Paulo Marcelo HoffLeadership: Oncologia D'OrStock and Other Ownership Interests: OncoStar Oncology ClinicsHonoraria: Bayer Health, United MedicalConsulting or Advisory Role: United Health Group, Bayer, Lilly, ExelixisResearch Funding: Bayer, MSD Oncology, Novartis, Exelixis, Roche/Genentech, AstraZeneca/MedImmune, Lilly Rodrigo DienstmannEmployment: OncoclínicasConsulting or Advisory Role: Roche, Boehringer IngelheimSpeakers' Bureau: Roche, Ipsen, Sanofi, MSD Oncology, Servier, Amgen, LibbsResearch Funding: Merck Matheus Costa e SilvaEmployment: Grupo Oncoclínicas, Rede D'Or São Luiz Rachel P. RiechelmannHonoraria: Novartis, Amgen, MSD Oncology, Servier, Roche/GenentechConsulting or Advisory Role: Bayer, Roche/Genentech, Ipsen, Astellas PharmaResearch Funding: Bayer, Roche/Foundation Medicine, AmgenNo other potential conflicts of interest were reported.

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.

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., (© 2020 S. Karger AG, Basel.)

Background: The standard treatment for localized squamous-cell carcinoma of the anal canal is definitive chemoradiotherapy. A meta-analysis of published studies conducted by our group showed significantly lower rates of disease-free survival (DFS) and overall survival at 3 years among HIV-positive patients. We aimed to compare detailed treatment outcomes between the groups of HIV-positive and -negative patients., Patients and Methods: We performed a retrospective multicenter study of a comparative cohort of consecutive patients with histologic diagnosis of localized squamous-cell carcinoma of the anal canal who received definitive chemoradiotherapy. Patients' characteristics and outcomes were compared according to HIV status. The primary end points were time to complete response (CR) and DFS time., Results: From June 2001 to September 2018, a total of 185 patients were included; 43 (30.2%) were HIV positive and 142 (69.8%) were HIV negative. The overall CR rates were 67.4% and 91.5% for HIV-positive and -negative patients, respectively (P < .001). The median follow-up was 47.8 months and the median time to experience CR was 7.8 months (95% confidence interval [CI], 5.7-10.5) for HIV-positive versus 4.89 months (95% CI, 4.54-5.25) for HIV-negative (P < .001) patients. The median DFS times were 79.7 months (95% CI, 56.8-102.6) and 127.9 months (95% CI, 112.6-143.2) for HIV-positive and -negative patients, respectively (P = .02). There was a trend toward greater grade 3/4 toxicity in the HIV-positive group., Conclusion: HIV-positive patients take longer to experience CR and present worse DFS. These findings have clinical implications because waiting longer to define CR among these patients may prevent unnecessary anorectal amputations., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

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.

Purpose: As of 2020, the world is facing the great challenge of the COVID-19 (Coronavirus disease 2019) pandemic, caused by the SARS-CoV-2 virus. While the overall mortality is low, the virus is highly virulent and may infect millions of people worldwide. This will consequently burden health systems, particularly by those individuals considered to be at high risk of severe complications from COVID-19. Such risk factors include advanced age, cardiovascular and pulmonary diseases, diabetes and cancer. However, few data on the outcomes of cancer patients infected by SARS CoV-2 exist. Therefore, there is a lack of guidance on how to manage cancer patients during the pandemic. We sought to propose specific recommendations about the management of patients with gastrointestinal malignancies., Methods: The Brazilian Gastrointestinal Tumours Group board of directors and members sought up-to-date scientific literature on each tumour type and discussed all recommendations by virtual meetings to provide evidence-based-and sometimes, expert opinion-recommendation statements. Our objectives were to recommend evidence-based approaches to both treat and minimise the risk of COVID-19 for cancer patients, and simultaneously propose how to decrease the use of hospital resources at a time these resources need to be available to treat COVID-19 patients., Results: Overall and tumour-specific recommendations were made by stage (including surgical, locoregional, radiotherapy, systemic treatments and follow-up strategies) for the most common gastrointestinal malignancies: esophagus, gastric, pancreas, bile duct, hepatocellular, colorectal, anal cancer and neuroendocrine tumours., Conclusions: Our recommendations emphasise the importance of treating cancer patients, using the best evidence available, while simultaneously taking into consideration the world-wide health resource hyperutilisation to treat non-cancer COVID-19 patients., Competing Interests: Rachel Riechelmann: honoraria and consultancy for Bayer, Astra Zeneca, Roche, Novartis, Ipsen, Servier. Research grants: Bayer, Amgen, Roche, Libbs. Renata D’Alpino Peixoto: honoraria and consultancy for Bayer, Roche, Lilly, Novartis, Ipsen, Amgen, Merck, EMS. Gustavo Fernandes: honoraria and consultancy for Bayer, Roche, Novartis, MSD. Research : BMS, Roche, MSD. Aline Chaves Andrade : honoraria and consultancy for Bayer, Novartis, Astra Zeneca, Ipsen, Amgen. Rui F Weschenfelder: honoraria and consultancy for Amgen, Bayer, Ipsen, Lilly, Merck, MSD, Sanofi, Roche. Juliana Florinda M Rêgo: honoraria and consultancy for Bayer, Novartis, Ipsen. Gabriel Prolla: none. Duilio Rocha Filho: honoraria and consultancy for Bayer, Merck Serono, Novartis, Ipsen, Servier Marcela Crosara: honoraria and consultancy for Lilly, MSD and Roche. Rene C Gansl: honoraria for Novartis and Ipsen Felipe Coimbra: none. Samuel Aguiar Jr: none. Elisangela Carvalho: none. Paulo M Hoff: none. Anelisa K Coutinho: honoraria and consultancy for Amgen, Bayer, Ipsen, Lilly, Merck, MSD, Roche, Sanofi, Servier., (© the authors; licensee ecancermedicalscience.)

Anal canal cancer is one of the human papilloma virus (HPV)-associated diseases with increasing incidence. High-risk sexual behaviour and the resurgence of human immunodeficiency virus (HIV) infection, associated with low HPV vaccine coverage, are risk factors for the increased incidence of this cancer. In this paper, the authors point out pertinent questions regarding the greater exposure of the population to some risk factors and discuss the latest epidemiological data of these factors, particularly those of concern to emerging countries like Brazil. The authors also discuss policies adopted that have not been successful to combat the HIV and HPV rise and that have direct consequences on the incidence of anal canal cancer., Competing Interests: The authors declare that they have no conflicts of interest., (© the authors; licensee ecancermedicalscience.)

Background: There are no randomized data to guide treatment decisions for patients with advanced pancreatic adenocarcinoma following first-line FOLFIRINOX. We performed a systematic review and meta-analysis of studies using gemcitabine-based chemotherapy after FOLFIRINOX to assess treatment efficacy and toxicity., Methods: We included studies published between 2011 and 2018 that evaluated the efficacy and toxicity of gemcitabine-based chemotherapy after FOLFIRINOX in patients with advanced pancreatic adenocarcinoma. We searched PubMed, Embase, Scopus, and Web of Science. Primary outcomes were objective response rate (ORR), disease control rate (DCR), any grade 3/4 toxicity rate, and progression-free survival (PFS). We used the random-effects model to generate pooled estimates for proportions., Results: Sixteen studies met the eligibility criteria. Overall, ORR was 10.8%, DCR was 41.1%, and any grade 3/4 toxicity rate was 28.6%. In subgroup analyses, gemcitabine plus nab-paclitaxel was associated with superior ORR (14.4 versus 8.4%; p  = 0.038) and DCR (53.5 versus 30.5%; p  < 0.001) compared with single-agent gemcitabine. Median PFS ranged from 1.9 to 6.4 months and numerically favored gemcitabine plus nab-paclitaxel., Conclusions: Our study suggests gemcitabine-based chemotherapy likely outperforms best supportive care after FOLFIRINOX in advanced pancreatic cancer. Also, gemcitabine plus nab-paclitaxel seems to be more active than single-agent gemcitabine (CRD42018100421)., Competing Interests: Conflict of interest statement: V.H.F.d.J. received honoraria from United Medical and had travel expenses payed by United Medical in the past 12 months. United Medical is the company responsible for the distribution and sale of nab-paclitaxel in Brazil. R.P.R. received consultancy fees from Astra Zeneca in the past 12 months., (© The Author(s), 2020.)

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., Competing Interests: None., (© the authors; licensee ecancermedicalscience.)

Background: Postoperative complications after gastric cancer resection vary in different series and they might have a significant impact in long-term outcomes. Our aim was to build a prediction rule on gastric cancer patients' overall and major morbidity risks., Methods: This retrospective study included 1223 patients from a single center who were resected between 1992 and 2016. Overall and major morbidity predictors were identified through multiple logistic regression. Models' performances were assessed through discrimination, calibration, and cross-validation, and nomograms were constructed., Results: The mean age was 61.3-year old and the male gender was more frequent (60%). The most common comorbidities were hypertension (HTN), diabetes, and chronic obstructive pulmonary disease (COPD). A D2-distal gastrectomy was the most frequent procedure and 87% of all lesions were located in the middle or distal third. Age, COPD, coronary heart disease, chronic liver disease, pancreatic resection, and operative time were independent predictors of overall and major morbidity. The extent of resection and splenectomy was associated with overall events and HTN with major ones. Both models were very effective in predicting events among patients at higher risk., Conclusions: The overall and major morbidity models and nomograms included clinical- and surgical-related data that were very effective in predicting events, especially for high-risk patients., (© 2019 Wiley Periodicals, Inc.)