Classification of early-stage colon cancer with Immunoscore®: clinical evidence and case studies.

Immunoscore® is a digital pathology diagnostic immunoassay used to complement tumor node metastasis staging for the prediction of recurrence risk in patients with early-stage colon cancer. In combination with standard clinicopathological features, Immunoscore informs adjuvant chemotherapy decision-making for patients with early-stage colon cancer. Immunoscore has been validated in patients with stage II/III colon cancer and demonstrated to be a stronger prognostic factor for survival than tumor node metastasis staging alone. Immunoscore improves the prognostic definition of patients with colon cancer, the identification of those patients at high risk of tumor recurrence, and the ability to predict which patients will derive most benefit from the use of adjuvant chemotherapy. Immunoscore has robust analytical performance characteristics which include good interlaboratory reproducibility and overall assay precision.

Plain language summary Immunoscore^® is a digital pathology diagnostic test that is used in addition to standard tools for assessing the severity and aggressiveness of tumors in patients with early-stage colon cancer. Immunoscore helps clinicians decide whether chemotherapy would be appropriate in these cases and, if so, for what duration. The test is currently used for patients with stage II or stage III colon cancer to guide treatment and is a good indicator of prognosis in colon cancers, helping to identify which patients are at a higher risk of tumor recurrence and which patients might benefit most from chemotherapy. Immunoscore is also a reliable and precise test, even when performed on different portions of a tumor sample.

Takotsubo Syndrome in the Perioperative Period: A Case Report and a Comprehensive Review of Pertinent Literature.

ABSTRACT: Stress-induced cardiomyopathy or takotsubo syndrome is a rare, nonischemic, heart condition resembling that of an acute coronary syndrome. Its distinctive feature is a transient wall motion abnormality occurring usually at the apical segment of the heart, with the degree of symptom manifestation and severity varying among patients. Although early data were supportive of a benign sequela and outcome, high degree of adverse events, such as acute heart failure and pulmonary edema, are anticipated, and the mortality rate approaches 5%. Hyperactivation of the sympathetic nervous system and adrenergic drugs have been pointed out as possible precipitators of the condition. Surgical procedures are a known cause of emotional and physical stress on patients, acting as an ideal substrate for the presentation of this syndrome. On occasion of a perioperative takotsubo syndrome case in a female patient during second-stage implant-based breast reconstruction, a review of the pertinent literature is presented. The acute onset and severity of the manifestations in this surgically uneventful procedure necessitated a multidisciplinary approach. Consequently, this report should raise awareness of the syndrome among plastic surgeons and anesthesiologists to promptly recognize and manage it effectively.

Alveolar bone histological necrosis observed prior to extractions in patients, who received bone-targeting agents.

OBJECTIVE: We reported the alveolar bone histology prior to dental extractions in cancer patients, who received bone-targeting agents (BTA). SUBJECTS AND METHODS: Fifty-four patients were included. Patients underwent extractions, and bone biopsies were taken. RESULTS: Extractions were performed due to pain, swelling, purulence, fistula, and numbness, not responding to treatment, in 40 patients (group A); extractions due to asymptomatic, non-restorable teeth, were performed in 14 patients (group B). Complete alveolar jaw bone histological necrosis was observed in 28 of 40 (70%) patients of group A and none of group B (p < .001). The development of clinical osteonecrosis (MRON) was assessed in 44 patients; 10 patients, who were also treated with Low Level Laser Treatments-LLLT, were excluded from this analysis, as the alternative therapies were a confounding factor. Twelve patients, with alveolar bone histological necrosis prior to extraction, developed medication-related osteonecrosis of the jaw (MRONJ) compared with two patients with vital or mixed vital/non-vital bone (p < .0007). BTAs >1 year and concurrent targeted therapy were also significantly associated with MRONJ (p = .016 and p = .050). CONCLUSION: Pain, swelling, purulence, fistula, and numbness were significantly associated with complete bone histological necrosis prior to extractions and increased MRONJ development. Research is justified to explore whether histological necrosis represents an early stage of osteonecrosis.

Treatment of relapsed urothelial bladder cancer with vinflunine: real-world evidence by the Hellenic Genitourinary Cancer Group.

Relapsed urothelial cancer represents an unmet medical need. Vinflunine is a third-generation antimicrotubuline inhibitor and is currently the only approved drug for second-line treatment across the European Union. We conducted a retrospective analysis assessing the efficacy and safety of vinflunine in 71 Greek patients with relapsed urothelial cancer who were treated between 2005 and 2014. An overall 84% of our patients received vinflunine as second-line treatment, 77% had a performance status of Eastern Cooperative Oncology Group scale 0 or 1, and 30% had liver metastasis at the time of vinflunine administration. A median of four cycles of vinflunine were administered (range 1-16). The most common reported adverse events were constipation, fatigue, and anemia. Median progression-free survival was 6.2 months (95% confidence interval: 4.4-8.8) and overall survival was 11.9 months (95% confidence interval: 7.4-21). Two patients (3%) achieved a complete remission, seven a partial remission (10%), and 22 (31%) had stable disease according to an intention-to-treat analysis. Hemoglobin level less than 10 g/dl and Eastern Cooperative Oncology Group performance status greater than 1 were independent adverse prognostic factors. Stratification according to the Bellmunt risk model was also associated with progression-free survival and overall survival in our population. Vinflunine appears to be a safe and effective treatment modality for relapsed urothelial cancer. More effective therapies and more accurate prognostic algorithms should be sought.

A systematic literature review of the human papillomavirus prevalence in locally and regionally advanced and recurrent/metastatic head and neck cancers through the last decade: The "ALARM" study.

AIMS: The aim of this systematic literature review was to provide updated information on human papillomavirus (HPV) prevalence in locally and regionally advanced (LA) and recurrent/metastatic (RM) head and neck cancer (HNC) worldwide. METHODS: Electronic searches were conducted on clinicaltrials.gov, MEDLINE/PubMed, Embase, and ASCO/ESMO journals of congresses for interventional studies (IS; Phase I-III trials) as well as MEDLINE and Embase for non-interventional studies (NIS) of LA/RM HNC published between January 01, 2010 and December 31, 2020. Criteria for study selection included: availability of HPV prevalence data for LA/RM HNC patients, patient enrollment from January 01, 2010 onward, and oropharyngeal cancer (OPC) included among HNC types. HPV prevalence per study was calculated as proportion of HPV+ over total number of enrolled patients. For overall HPV prevalence across studies, mean of reported HPV prevalence rates across studies and pooled estimate (sum of all HPV+ patients over sum of all patients enrolled) were assessed. RESULTS: Eighty-one studies (62 IS; 19 NIS) were included, representing 9607 LA/RM HNC cases, with an overall mean (pooled) HPV prevalence of 32.6% (25.1%). HPV prevalence was 44.7% (44.0%) in LA and 24.3% (18.6%) in RM. Among 2714 LA/RM OPC patients from 52 studies with available data, mean (pooled) value was 55.8% (50.7%). The majority of data were derived from Northern America and Europe, with overall HPV prevalence of 46.0% (42.1%) and 24.7% (25.3%) across studies conducted exclusively in these geographic regions, respectively (Northern Europe: 31.9% [63.1%]). A "p16-based" assay was the most frequently reported HPV detection methodology (58.0%). CONCLUSION: Over the last decade, at least one quarter of LA/RM HNC and half of OPC cases studied in IS and NIS were HPV+. This alarming burden is consistent with a potential implication of HPV in the pathogenesis of at least a subgroup of HNC, underscoring the relevance of HPV testing and prophylaxis to HNC prevention and management.

The Impact of Expert Pathology Review and Molecular Diagnostics on the Management of Sarcoma Patients: A Prospective Study of the Hellenic Group of Sarcomas and Rare Cancers.

Precise classification of sarcomas is crucial to optimal clinical management. In this prospective, multicenter, observational study within the Hellenic Group of Sarcoma and Rare Cancers (HGSRC), we assessed the effect of expert pathology review, coupled with the application of molecular diagnostics, on the diagnosis and management of sarcoma patients. Newly diagnosed sarcoma patients were addressed by their physicians to one of the two sarcoma pathologists of HGSRC for histopathological diagnostic assessment. RNA next-generation sequencing was performed on all samples using a platform targeting 86 sarcoma gene fusions. Additional molecular methods were performed in the opinion of the expert pathologist. Therefore, the expert pathologist provided a final diagnosis based on the histopathological findings and, when necessary, molecular tests. In total, 128 specimens from 122 patients were assessed. Among the 119 cases in which there was a preliminary diagnosis by a non-sarcoma pathologist, there were 37 modifications in diagnosis (31.1%) by the sarcoma pathologist, resulting in 17 (14.2%) modifications in management. Among the 110 cases in which molecular tests were performed, there were 29 modifications in diagnosis (26.4%) through the genomic results, resulting in 12 (10.9%) modifications in management. Our study confirms that expert pathology review is of utmost importance for optimal sarcoma diagnosis and management and should be assisted by molecular methods in selected cases.

Exploring the Use of a Digital Platform for Cancer Patients to Report Their Demographics, Disease and Therapy Characteristics, Age, and Educational Disparities: An Early-Stage Feasibility Study.

INTRODUCTION: The increasing burden of cancer, the development of novel therapies, and the COVID-19 pandemic have made cancer care more complex. Digital innovation was then pushed toward developing platforms to facilitate access to cancer care. Age, education, and other disparities were, however, shown to limit the use of the digital health innovation. The aim of this early-stage feasibility study was to assess whether Greek cancer patients would register at CureCancer and self-report their demographics, disease and therapy characteristics, and socioeconomic issues. The study was organized by the Hellenic Society of Medical Oncology. METHODS: Patients from nine cancer centers were invited to register on the CureCancer platform and complete an anonymous questionnaire on demographics, disease and therapy characteristics, and socioeconomic issues. Patients were also encouraged to upload, in a secure area for them, their medical files and share them with their physicians. They were then asked to comment on their experience of registration and how easy it was to upload their medical files. RESULTS: Of the 159 patients enrolled, 144 (90.56%) registered, and 114 of those (79.16%) completed the questionnaire, suggesting that the study is feasible. Users' median age was 54.5 years, and 86.8% of them were university and high school graduates. Most patients (79.8%) reported their specific type of cancer diagnosis, and all reported their therapy characteristics. Breast and lung cancers were the most common. A total of 87 patients (76.3%) reported being on active cancer therapy, 46 (40.4%) had metastatic disease, and 51 (44.7%) received supportive care medications. Eighty-one (71.05%) patients received prior cancer therapies, and twenty-seven recalled prior supportive care medications. All patients reported visiting non-oncology Health Care Professionals during the study. Nineteen of 72 (26.39%) patients who worked prior to cancer diagnosis changed work status; 49 (42.98) patients had children under 24 years; and 16 (14%) patients lived alone. Nine (7.9%) patients were members of patient associations. Registration was "much/very much" easy for 98 (86.0%) patients, while 67 (58.8%) had difficulties uploading their files. Patients commented on the well-organized data access, improved communication, feeling safe, medication adherence, interventions from a distance, and saving time and money. Over 80% of patients "preferred the digital way". DISCUSSION: A total of 114 patients succeeded in registering on the digital platform and reporting their demographics, disease and therapy characteristics, and socioeconomic issues. Age and educational disparities were disclosed and highlighted the need for educational programs to help older people and people of lower education use digital innovation. Health care policy measures would support patients' financial burden associated with work changes, living alone, and children under 24 years old at school or college. Policy actions would motivate patients to increase their participation in patient associations. According to the evidence DEFINED framework, the number of patients, and the focus on enrollment, engagement, and user experience, the study fulfills actionability level criterion 1.

Molecular Epidemiology and Treatment Patterns of Patients With EGFR Exon 20-Mutant NSCLC in the Precision Oncology Era: The European EXOTIC Registry.

Introduction: Real-world evidence regarding molecular epidemiology and management patterns of patients with EGFR exon-20 mutated, advanced NSCLC outside the context of clinical trials is lacking. Methods: We created a European registry for patients with advanced EGFR exon 20-mutant NSCLC diagnosed from January 2019 to December 2021. Patients enrolled in clinical trials were excluded. Clinicopathologic and molecular epidemiology data were collected, and treatment patterns were recorded. Clinical end points according to treatment assignment were assessed using Kaplan-Meier curves and Cox regression models. Results: Data on 175 patients from 33 centers across nine countries were included in the final analysis. Median age was 64.0 (range: 29.7-87.8) years. Main features included female sex (56.3%), never or past smokers (76.0%), adenocarcinoma (95.4%), and tropism for bone (47.4%) and brain (32.0%) metastases. Mean programmed death-ligand 1 tumor proportional score was 15.8% (range: 0%-95%) and mean tumor mutational burden was 7.06 (range: 0-18.8) mutations per megabase. Exon 20 was detected in the tissue (90.7%), plasma (8.7%), or both (0.6%), using mostly targeted next-generation sequencing (64.0%) or polymerase chain reaction (26.0%). Mutations were mainly insertions (59.3%), followed by duplications (28.1%), deletions-insertions (7.7%), and the T790M (4.5%). Insertions and duplications were located mainly in the near loop (codons 767-771, 83.1%) and the far loop (codons 771-775, 13%) and only in 3.9% within the C helix (codons 761-766). Main co-alterations included mutations in TP53 (61.8%) and MET amplifications (9.4%). Treatment on mutation identification included chemotherapy (CT) (33.8%), CT-immunotherapy (IO) (18.2%), osimertinib (22.1%), poziotinib (9.1%), mobocertinib (6.5%), mono-IO (3.9%), and amivantamab (1.3%). Disease control rates were 66.2% with CT plus or minus IO, 55.8% with osimertinib, 64.8% with poziotinib, and 76.9% with mobocertinib. Corresponding median overall survival was 19.7, 15.9, 9.2, and 22.4 months, respectively. In multivariate analysis, type of treatment (new targeted agents versus CT ± IO) affected progression-free survival (p = 0.051) and overall survival (p = 0.03). Conclusions: EXOTIC represents the largest academic real-world evidence data set on EGFR exon 20-mutant NSCLC in Europe. Indirectly compared, treatment with new exon 20-targeting agents is likely to confer survival benefit than CT plus or minus IO.

A Real-world Multicenter Prospective Study of Everolimus in Pancreatic Neuroendocrine Tumors: The 'PROTOR' Study.

BACKGROUND/AIM: Pancreatic neuroendocrine tumors (panNETs) are rare neoplasms with challenging disease management. We aimed to evaluate the progression-free survival (PFS) and overall response rate (ORR) in chemotherapy-naïve patients with unresectable or metastatic Grade (G) 1-2 panNETs treated with everolimus in the routine care in Greece. PATIENTS AND METHODS: This was a multicenter, prospective, observational study. Eligible patients were recently (≤4 weeks) initiated on treatment with everolimus and were followed for up to 48 months. RESULTS: Nineteen eligible patients (mean age 55.1 years) were enrolled. All patients had metastatic disease and 84.2% had G2 panNET. Everolimus was initiated in combination with somatostatin analogues in 84.2% of the patients. The mean everolimus treatment duration was 21.5 months. The median Kaplan-Meier-estimated PFS was 20.4 months (95% confidence interval=14.1-41.5). The ORR was 27.8%. The rate of everolimus-related adverse events was 84.2% (Grade ≥3: 31.6%). CONCLUSION: Everolimus displayed clinical benefit and a predictable safety profile in pancreatic neuroendocrine tumors.

Portal-mesenteric vein resection for pancreatic cancer: Results in par with the defined benchmark outcomes.

Background: Patients with pancreatic cancer (PC), which may involve major peripancreatic vessels, have been generally excluded from surgery, as resection was deemed futile. The purpose of this study was to analyze the results of portomesenteric vein resection in borderline resectable or locally advanced PC. This study comprises the largest series of such patients in Greece. Materials and Methods: Investigator-initiated, retrospective, noncomparative study of patients with borderline resectable or locally advanced adenocarcinoma undergoing pancreatectomy en-block with portal and/or superior mesenteric vein resection in a tertiary referral center in Greece between January 2014 and October 2021. Follow-up was complete up to December 2021. Operative and outcome measures were determined. Results: Forty patients were included. Neoadjuvant therapy was administered to only 58% and was associated with smaller tumor size (median: 2.9 cm vs. 4.2 cm, p = 0.004), but not with increased survival. Though venous wall infiltration was present in 55%, it was not associated with tumor size, or Eastern Cooperative Oncology Group (ECOG) status. Resection was extensive: a median of 27 LNs were retrieved, R0 resection rate (≥1 mm) was 87%, and median length of resected vein segments was 3 cm, requiring interposition grafts in 40% (polytetrafluoroethylene). Median ICU stay was 0 days and length of hospitalization 9 days. Postoperative mortality was 2.5%. Median follow-up was 46 months and median overall survival (OS) was 24 months. Two-, 3- and 5-year OS rates were 49%, 33%, and 22% respectively. All outcomes exceeded benchmark cutoffs. Lower ECOG status was positively correlated with longer survival (ECOG-0: 32 months, ECOG-1: 24 months, ECOG-2: 12 months, p = 0.02). Conclusion: This series of portomesenteric resection in borderline resectable or locally advanced PC demonstrated a median survival of 2 years, extending to 32 months in patients with good performance status, which meet or exceed current outcome benchmarks.

A Multicenter, Prospective, Observational Study to Assess the Clinical Activity and Impact on Symptom Burden and Patients' Quality of Life in Patients with Advanced Soft Tissue Sarcomas Treated with Trabectedin in a Real-World Setting in Greece.

This non-interventional, multicenter, prospective study aimed to evaluate the real-world activity of trabectedin, and its impact on symptom burden and quality of life in patients with advanced soft tissue sarcoma (aSTS) treated in routine clinical settings in Greece. Patients with histologically confirmed aSTS newly initiated on trabectedin were enrolled. The primary endpoint was progression-free survival (PFS) rate at 6 months. Secondary endpoints included PFS rate at 3 months, median PFS, objective response rate (ORR), disease control rate (DCR), overall survival (OS), and an assessment of the impact of treatment on health-related quality of life (HRQoL), cancer-related symptom burden and symptom interference with function, as well as all-cause treatment discontinuation rate. A total of 64 eligible patients from 13 Greek centers were evaluated. Patients received a median of three trabectedin cycles per patient (interquartile range [IQR]: 2.0-6.0). Median PFS was 6.6 months with 67.9% and 51.2% of patients free from progression at 3 and 6 months, respectively. ORR was 7.8% and DCR 21.9%. Median OS was 13.1 months. No significant changes from enrolment were noted in HRQoL scores. In total, 30 patients (46.9%) had at least one trabectedin-related adverse drug reaction (ADR) and 9 (14.1%) at least one serious ADR. The treatment discontinuation rate due to toxicity was 9.4%. These results suggest that trabectedin is an active treatment with clinically meaningful benefits in patients with aSTS with no new safety signals.

Front-Line Bevacizumab plus Chemotherapy with or without Maintenance Therapy for Metastatic Breast Cancer: An Observational Study by the Hellenic Oncology Research Group.

Front-line bevacizumab (BEV) in combination with taxanes offers benefit in progression-free survival (PFS) in metastatic breast cancer (mBC). The medical records of mBC patients, treated with front-line BEV-based chemotherapy, were retrospectively reviewed in order to generate real life safety and efficacy data. Patients with human epidermal growth factor receptor 2 (HER2)-negative mBC treated with front-line BEV in combination with chemotherapy were eligible. Maintenance therapy with BEV and/or hormonal agents was at the physicians' discretion. Among the 387 included patients, the most common adverse events were anemia (61.9%, mainly grade 1), grade 3/4 neutropenia (16.5%), grade 1/2 fatigue (22.3%), and grade 1/2 neuropathy (19.6%). Dose reductions were required in 164 cycles (7.1%) and toxicity led to treatment discontinuation in 21 patients (5.4%). The median PFS and the median overall survival (OS) were 13.3 (95% CI: 11.7-14.8) and 32.3 months (95% CI: 27.7-36.9), respectively. Maintenance therapy, with hormonal agents (ET) and/or BEV, was associated with longer OS versus no maintenance therapy (47.2 versus 23.6 months; p < 0.001) in patients with hormone receptor (HR)-positive disease and BEV maintenance offered longer OS versus no maintenance in patients with HR-negative disease (52.8 versus 23.3; p = 0.023). These real-life data show that front-line BEV-based chemotherapy in HER2-negative mBC patients is an effective treatment with an acceptable toxicity profile. The potential benefit of maintenance treatment, especially ET, is important and warrants further research.

Validation of Patras Immunotherapy Score model for prediction and prognosis of patients with advanced NSCLC treated with nivolumab or pembrolizumab: results from a European multicentre study.

Background: Recently, the Patras Immunotherapy Score (PIOS) has been developed to estimate the survival benefit of patients with advanced non-small-cell lung cancer (aNSCLC) treated with nivolumab or pembrolizumab. The aim of this study was to validate the clinical value of PIOS in an external cohort of aNSCLC patients. Methods: PIOS is a baseline formula produced by the combination of performance status, body mass index, age and line of treatment. In this multicentre study, 626 patients with confirmed NSCLC pathology, who had been treated with nivolumab or pembrolizumab, as well as 444 patients with aNSCLC, who had been managed with chemotherapy alone, were retrospectively enrolled. Predictive and prognostic values of PIOS were finally evaluated. Results: Patients treated with immunotherapy and higher PIOS score had an improved progression-free survival not only in univariate [hazard ratio (HR) = 0.621, p = 0.001], but also in multivariable analysis (HR = 0.651, p = 0.003). In addition, improved overall survival with increasing PIOS score was also observed (HR = 0.608, p < 0.001) with this association remaining statistically significant after adjusting for programmed-cell death ligand 1 (PD-L1) expression (HR = 0.620, p < 0.001). In addition, patients with disease progression (PD) had lower scores compared to those with stable disease (SD), partial response (PR) or complete response (CR) in a two-tier model (p < 0.001) as well as in a four-tier model (PD, SD, PR and CR; p < 0.001). Prognostic significance of PIOS score also persisted using a binary logistic regression analysis, adjusted for disease stage and PD-L1 status (p = 0.002, odds ratio: 0.578). Contrarily, PIOS had no prognostic significance in the chemotherapy group; however, upon combined analysis of the two cohorts, PIOS was found to have a significant interaction with the type of treatment (HR = 0.066 with p < 0.001), confirming its predictive value for immunotherapy. Conclusions: This study provides further validation of PIOS in aNSCLC patients treated with anti-PD-1 monotherapy.

Palatine tonsil metastasis of cecal mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN): A unique case.

This case demonstrates the importance of understanding that patients with malignant neoplasms may exhibit metastases in unexpected sites and illustrates the necessity of a thorough clinical examination and pathologic correlation.

The Impact of Thromboprophylaxis on the Survival of Patients with Advanced Pancreatic Cancer. The Pancreatic Cancer and Tinzaparin (PaCT) Study.

Pancreatic cancer (PaC) induces a prothrombotic and hypercoagulable state. The aim of this study was to investigate the effect of tinzaparin in combination with chemotherapy. The PaCT (pancreatic cancer and tinzaparin) study was a retrospective observational study that collected data regarding progression free survival (PFS) in advanced or metastatic PaC patients who received thromboprophylaxis with tinzaparin during chemotherapy with nab-paclitaxel (N) and gemcitabine (G). The primary end point was to compare, from already published data, the PFS of patients receiving thromboprophylaxis with tinzaparin with the PFS of patients receiving chemotherapy with N-G but no thromboprophylaxis. Secondary end points were efficacy and safety of anticoagulation. In total, 110 PaC patients, 93% with advanced or metastatic disease, treated with N-G and tinzaparin (10,291 ± 1176 Anti-Xa IU, OD, median duration 8.7, IQR: 5.6-11.9 months) were enrolled. Of these, 52% were males and; the median age was 68 (40-86 years). The tumor was located to in the pancreatic head at in 45% of the patients. The median PFS was 7.9 months (IQR: 5.0-11.8 months). Out of 14 similar studies (involving 2994 patients) identified via systematic search, it was determined that the weighted PFS of patients receiving N-G but no anticoagulation was 5.6 months. Therefore, patients receiving tinzaparin had 39.54% higher PFS than patients without thromboprophylaxis (p < 0.05). During the follow-up period of 18.3 ± 11.7 months, three (2.7%) thrombotic events were recorded while two clinically relevant non-major bleeding events occurred (1.9%). In conclusion, PFS in advanced PaC patients undergoing chemotherapy is positively impacted by anticoagulation. Thromboprophylaxis with tinzaparin in treatment dose is efficient and safe.

Distal pancreatectomy with celiac axis resection (DP-CAR): Optimal perioperative outcome in a patient with locally advanced pancreas adenocarcinoma.

INTRODUCTION: Distal pancreatectomy with en bloc celiac axis resection (DP-CAR) is an operation technically demanding, uncommonly performed, even in high-volume pancreatic centers, which may offer a curative resection in patients with locally advanced cancer of the body of the pancreas, otherwise considered unresectable. PRESENTATION OF CASE: We present, in clinical and technical detail, a patient with DP-CAR with a very good intraoperative and postoperative course, no complications, short hospital stay, and histology consistent with a curative resection. DISCUSSION: Because of the scarcity of DP-CAR, even high-volume individual centers have been able to gather relatively limited experience, and only in a time frame of more than a decade each. CONCLUSION: DP-CAR can be curative for a minority of patients with pancreatic adenocarcinoma and is performed only in centers with a long, dedicated interest in advanced pancreatic surgery with a well-known track record in resection of borderline and locally advanced pancreatic cancer involving major peripancreatic veins.

Tumor Mutational Patterns and Infiltrating Lymphocyte Density in Young and Elderly Patients With Breast Cancer.

BACKGROUND/AIM: Age may pertain to different tumor genotype characteristics which may interfere with treatment efficacy and prognosis. We investigated the distribution and prognostic effect of mutations and tumor infiltrating lymphocyte (stromal TIL density) in young (≤35 years) and elderly (>65 years) early breast cancer patients. MATERIALS AND METHODS: Paraffin tumor genotypes of all clinical subtypes from 345 patients were examined. RESULTS: A total of 638 mutations were detected in 221 patients (64.1%). Compared to young, elderly patients presented with lower TIL density (p<0.001) but more TILs in TP53 mutated tumors (p=0.042). Mutation in one, rather than in 2 or more genes, conferred better outcome (DFS: HR=0.51, p=0.016; OS: HR=0.47, p=0.015) but the effect was age-independent. CONCLUSION: There are fewer TILs and different mutations patterns in tumors from elderly patients compared to young. Age and TIL-independent gene agnostic co-mutations affect patient outcome.

A Patient Affected with Serous Ovarian/Peritoneal Carcinoma Carrying the FANCM Mutation.

We report a case of a 58-year-old female with ovarian cancer. The patient presented with ascites, and the biopsies revealed a low-grade adenocarcinoma, either a serous papillary ovarian cancer with peritoneal implants or a primary peritoneal carcinoma. She received neoadjuvant chemotherapy and after 5 cycles achieved partial response, and then, she underwent a total hysterectomy/bilateral salpingo-oophorectomy. The patient underwent germline gene-panel testing for the detection of mutations in cancer predisposing genes. A truncating mutation in the Fanconi anemia complementation group M (FANCM) gene was detected in heterozygosity, namely, p.Arg658Ter (c.1972C>T, rs368728266). The patient's family history is unremarkable, with no reported cases of breast or ovarian cancer, a fact that can be attributed to the significant lower penetrance of FANCM mutations.