Prognostic Factors Influencing Survival in Ovarian Cancer Patients: A 10-Year Retrospective Study.

OBJECTIVE: To analyze the factors associated with overall survival (OS) and progression-free survival (PFS) in patients with ovarian cancer in Cyprus. METHODS: We retrospectively analyzed data from patients with histologically confirmed epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC). RESULTS: A total of 106 women diagnosed with ovarian cancer were included, with a median age at diagnosis of 58 years. The Kaplan-Meier survival analysis showed a median OS of 41 months (95% C.I = 36.9, 45.1), and the FIGO stage (p < 0.001), type of surgery (p < 0.001) and performance status (p < 0.001) were identified as statistically significant prognostic factors for OS. PFS analysis revealed the FIGO stage (p = 0.006) and the performance status (p < 0.001) as significant prognostic factors. Additionally, a Cox regression analysis for median OS was performed for patients with high-grade serous carcinoma, identifying the performance status, FIGO stage, and type of surgery as prognostic factors in univariate analysis. However, in the subsequent multivariate analysis, the performance status and the FIGO stage were confirmed to be the only statistically significant prognostic factors for OS (p < 0.05). CONCLUSIONS: This study confirms that the FIGO stage, performance status, and surgery type were considered as prognostic factors for OS in ovarian cancer.

COVID-19 Emotional and Mental Impact on Cancer Patients Receiving Radiotherapy: An Interpretation of Potential Explaining Descriptors.

Background: Significant changes in the accessibility and viability of health services have been observed during the COVID-19 period, particularly in vulnerable groups such as cancer patients. In this study, we described the impact of radical practice and perceived changes on cancer patients' mental well-being and investigated potential outcome descriptors. Methods: Generalized anxiety disorder assessment (GAD-7), patient health (PHQ-9), and World Health Organization-five well-being index (WHO-5) questionnaires were used to assess anxiety, depression, and mental well-being. Information on participants, disease baseline information, and COVID-19-related questions were collected, and related explanatory variables were included for statistical analysis. Results: The mean score values for anxiety, depression, and mental well-being were 4.7 ± 5.53, 4.9 ± 6.42, and 72.2 ± 18.53, respectively. GAD-7 and PHQ-9 scores were statistically associated (p < 0.001), while high values of GAD-7 and PHQ-9 questionnaires were related to low values of WHO-5 (p < 0.001).Using the GAD-7 scale, 16.2% of participants were classified as having mild anxiety (GAD-7 score: 5−9).Mild to more severe anxiety was significantly associated with a history of mental health conditions (p = 0.01, OR = 3.74, 95% CI [1.372−10.21]), and stage category (stage III/IV vs. I/II, p = 0.01, OR = 3.83, 95% CI [1.38−10.64]. From the participants, 36.2% were considered to have depression (PHQ-9 score ≥ 5). Depression was related with older patients (p = 0.05, OR = 1.63, 95% CI [1.16−2.3]), those with previous mental health conditions (p = 0.03, OR = 14.24, 95% CI [2.47−81.84]), those concerned about the COVID-19 impact on their cancer treatment (p = 0.027, OR = 0.19, 95% CI [0.045−0.82]) or those who felt that COVID-19 pandemic has affected mental health (p = 0.013, OR = 3.56, 95% CI [1.30−9.72]). Additionally, most participants (86.7%) had a good well-being score (WHO-5 score ≥ 50). Mental well-being seemed more reduced among stage I−III patients than stage IV patients (p = 0.014, OR = 0.12, 95% CI [0.023−0.65]). Conclusion: There is a necessity for comprehensive cancer care improvement. These patients' main concern related to cancer therapy, yet the group of patients who were mentally affected by the pandemic should be identified and supported.

Outcomes of 556 consecutive patients with stage I-III colon cancer managed in a single center over 10 years.

BACKGROUND: The Bank of Cyprus Oncology Center is the largest cancer center in Cyprus, providing standalone oncology services to a population of just under a million. METHODS: The aim of the study was to calculate disease-free survival (DFS) and overall survival (OS) for consecutive patients with stage I-III colon cancer over a 10-year period, by collecting retrospective data from patients' medical charts. RESULTS: We identified 556 patients with a median age at diagnosis of 67 (range 18-88). The majority of them were male (60%). Just over half of stage II patients received chemotherapy: capecitabine (44%) and FOLFOX/CapeOx (7%). Treatment administered in stage III was as follows: CapeOx (48%); FOLFOX (28%); capecitabine (12%); 5-fluorouracil (4%); and 8% received no treatment. DFS at 5 years was: stage I 90%; stage II 85%; and stage III 69%. Cancer-specific OS at 5 years was: stage I 94%; stage II 93%; and stage III 81%. Favorable outcomes were also maintained at 10 years (stage I 94%; stage II 84%; and stage III 70%). On multivariate analysis, only stage was statistically significant as a prognostic factor, whereas high-risk features (pT4±pN2), disease location (right vs. left), and age >70 years old did not reach statistical significance. CONCLUSIONS: Despite our country's fragmented healthcare system, with multiple referring surgeons from the private and public sectors, the outcomes achieved were highly consistent with those published in the international literature. This can be attributed to optimal multidisciplinary management and follow-up care.

Irreversible Electroporation (IRE) Combined With Chemotherapy Increases Survival in Locally Advanced Pancreatic Cancer (LAPC).

OBJECTIVES: Locally advanced pancreatic cancer (LAPC) is found in about 40% of patients with pancreatic cancer. Irreversible electroporation (IRE) is a nonthermal ablative technique that provides an alternative in patients with LAPC and can be safely combined with chemotherapy. MATERIALS AND METHODS: From 2015 until October of 2019, we performed laparotomic IRE in a total of 40 patients with stage III LAPC. The median age of these patients was 65.2 years (range: 46 to 81 y), and the median tumor size was 3.8 cm (range: 2 to 5.2 cm). 33 of 40 patients were treated preoperatively with FOLFIRINOX or nab-paclitaxel plus gemcitabine and in case of disease control, IRE was performed, whereas in 7 patients, IRE was performed without previous chemotherapy. RESULTS: All patients were treated successfully with IRE as the tumor evaluation showed no disease progression after the completion of induction chemotherapy. No IRE-related deaths occurred. Two major grade III complications were reported: pancreatic fistula grade A in 8 patients and 3 patients diagnosed with delayed gastric emptying. Up to October 31, 2019, the median overall survival (OS) of all patients was 24.2 months (range: 6 to 36 mo), and the median progression-free survival was 10.3 months (range: 3 to 24 mo). After the completion of IRE, 30 patients (75%) continued with adjuvant chemotherapy. Fifteen patients (37%) have >24 months OS and 3 patients (8%) have reached 36 months OS and are still alive. CONCLUSION: The combination of chemotherapy with IRE, which is a safe and effective procedure, may result in a survival benefit for patients with LAPC.

A phase I trial of adoptive transfer of allogeneic natural killer cells in patients with advanced non-small cell lung cancer.

HLA-mismatched natural killer (NK) cells have shown efficacy in acute myeloid leukemia, and their adoptive transfer in patients with other malignancies has been proven safe. This phase I clinical trial was designed to evaluate safety (primary endpoint) and possible clinical efficacy (secondary endpoint) of repetitive administrations of allogeneic, in vitro activated and expanded NK cells along with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Patients with unresectable, locally advanced/metastatic NSCLC receiving 1st/2nd line chemotherapy were eligible to receive 2-4 doses of activated NK cells from two relative donors. Donor's CD56(+) cells were cultured for 20-23 days with interleukin-15 (IL-15) and hydrocortisone (HC) and administered intravenously between chemotherapy cycles. Premedication with corticosteroids and/or H1 inhibitors was allowed. Sixteen patients (performance status 0-1) with adenocarcinoma (n = 13) or squamous cell carcinoma (n = 3) at stage IIIb (n = 5) or IV (n = 11) receiving 1st (n = 13) or 2nd (n = 3) line treatment were enrolled. Fifteen patients received 2-4 doses of allogeneic activated NK cells (0.2-29 × 10(6)/kg/dose, median 4.15 × 10(6)/kg/dose). No side effects (local or systemic) were observed. At a median 22-month follow-up (range, 16.5-26 months) 2 patients with partial response and 6 patients with disease stabilization were recorded. Median progression free survival and overall survival were 5.5 and 15 months, respectively. A 56% 1-year survival and a 19% 2-year survival were recorded. In conclusion, repetitive infusions of allogeneic, in vitro activated and expanded with IL-15/HC NK cells, in combination with chemotherapy are safe and potentially clinically effective.

Synchronous presentation of GISTs and other primary neoplasms: a single center experience.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are common mesenchymal neoplasms of the digestive tract and may occasionally arise within the abdomen without gastrointestinal tract connection. GISTs have recently attracted widespread interest because of the development of effective targeted molecular agents against it. While synchronous occurrence of a GIST with a tumor of different histogenesis was thought to be very rare, it is now apparent that they are more common than previously believed. PATIENTS AND METHODS: We report our experience with GISTs and also six cases of GIST coexisting with other primary neoplasms. Using immunohistochemistry and mutational analysis, a possible correlation was investigated. A review of the literature was also conducted. RESULTS: There were no significant differences in the immumohistochemical and molecular profile between single GISTs and GISTs coexisting with other tumors, nor was there any mutational correlation between GISTs and the coexistent tumors of different histogenesis regarding KIT and PDGFRA genes. CONCLUSION: Further molecular biology studies are required in order to investigate thoroughly the simultaneous development of tumors with different histotypes.

Consensus statement of the Hellenic and Cypriot Gastric Cancer Study Group on the diagnosis, staging and management of gastric cancer.

Gastric Cancer epidemics have changed over recent decades, declining in incidence, shifting from distal to proximal location, transforming from intestinal to diffuse histology. Novel chemotherapeutic agents combined with modern surgical operations hardly changed overall disease related survival. This may be attributed to a substantial inherent geographical variation of disease genetics, but also to a failure to standardize and implement treatment protocols in clinical practice. To overcome these drawbacks in Greece and Cyprus, a Gastric Cancer Study Group under the auspices of the Hellenic Society of Medical Oncology (HeSMO) and Gastrointestinal Cancer Study Group (GIC-SG) merged their efforts to produce a consensus considering ethnic parameters of healthcare system and the international proposals as well. Utilizing structured meetings of experts, a consensus was reached. To achieve further consensus, statements were subjected to the Delphi methodology by invited multidisciplinary national and international experts. Sentences were considered of high or low consensus if they were voted by ≥ 80%, or < 80%, respectively; those obtaining a low consensus level after both voting rounds were rejected. Forty-five statements were developed and voted by 71 experts. The median rate of abstention per statement was 9.9% (range: 0-53.5%). At the end of the process, one statement was rejected, another revised, and all the remaining achieved a high consensus. Forty-four recommendations covering all aspects of the management of gastric cancer and concise treatment algorithms are proposed by the Hellenic and Cypriot Gastric Cancer Study Group. The importance of centralization, care by a multidisciplinary team, adherence to guidelines, and individualization are emphasized.

Expression and prognostic significance of kallikrein-related peptidase 8 protein levels in advanced ovarian cancer by using automated quantitative analysis.

Kallikrein-related peptidases, a subgroup of the serine protease enzyme family, are considered to be important prognostic biomarkers in cancer. In this study we sought to determine the prognostic value of kallikrein-related peptidase 8 (KLK8, hK8, KLK-8) in ovarian cancer using a novel method of compartmentalised in situ protein analysis. A tissue array composed of 150 advanced stage ovarian cancers, uniformly treated with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For the evaluation of kallikrein-related peptidase 8 protein expression, we used an immunofluorescence-based method of automated in situ quantitative protein analysis (AQUA). Mean follow-up time of the cohort was 34.35 months. One hundred twenty-six of 150 cases had sufficient tissue for AQUA analysis. There were significant correlations between tumour mask KLK8 protein expression levels and clinicopathological variables, including grade (p = 0.0011), residual disease (p = 0.0063) and clinical response to chemotherapy(p = 0.0346). In univariate survival analysis there was a significant correlation between KLK8 tumour mask expression and five years progression-free survival, meanwhile it was not associated with five-year overall survival (p = 0.0694). Specifically, low KLK8 expression correlated with better outcome (top vs. bottom quartile, p = 0.0319). In multivariate survival analysis, adjusting for well-characterised prognostic variables, tumour KLK8 expression level retained its prognostic significance for progression-free survival (95%CI: 0.341-1.027, p = 0.045). The possibility that KLK8 may be a suitable candidate as a diagnostic and prognostic marker warrants further investigation.

Salvage therapy of pretreated advanced breast cancer with bevacizumab and paclitaxel every two weeks: a retrospective case review study.

BACKGROUND: Targeting angiogenesis is nowadays one of the most promising approaches for breast cancer. Bevacizumab (BEV), a VEGF-trap monoclonal antibody, was recently approved in combination with paclitaxel (PAC) for the first line treatment of advanced breast cancer (ABC). The activity of this combination in pretreated patients is not known. METHODS: Patients with pretreated ABC and progressive disease received BEV 10 mg/kg with PAC 135 mg/m(2) every two weeks for six months and then maintenance with BEV 15 mg/kg every three weeks until progression. This regimen was chosen for better patient convenience, while maintaining the same dose intensity for both drugs. RESULTS: 42 patients were reviewed retrospectively (41 f, 1 m, mean age 57 years). Overall response rate was 35.7%. Stable disease was observed in 45.2% of patients, whereas 14.3% of patients progressed. The median overall survival was greater than 20 months, with a one year rate of 83.4%. The median progression free survival was 12.1 months, with a one year rate of 51.8%. Toxicity was in general acceptable. CONCLUSION: This biweekly BEV/PAC combination seems to be active with acceptable toxicity in pretreated ABC with an advantage over the weekly regimen regarding quality of life and preservation of resources.

Paraneoplastic cerebellar degeneration in a patient with pseudomyxoma peritonei and breast cancer: case report and literature review.

The case of a 31-year-old woman with progressive cerebellar degeneration preceding by several months the diagnosis and treatment of breast cancer initially and pseudomyxoma peritonei (PMP) with evidence of causative association with the latter is presented. Despite various chemotherapeutic and surgical manipulations, the patient did not substantially improve and succumbed 20 months following initial diagnosis of the neurological disorder. Interestingly, neurological symptoms partially regressed transiently only after surgical debulking of the PMP and not after the remission of breast cancer after various chemotherapeutic regimens suggesting an etiological relationship of the former and the cerebellar degeneration. Early recognition and appropriate therapy of this rare complication of PMP is imperative as it may be crucial for the outcome.

Defining molecular phenotypes of human papillomavirus-associated oropharyngeal squamous cell carcinoma: validation of three-class hypothesis.

OBJECTIVE: The purpose of this study was to determine if oropharyngeal squamous cell carcinoma (OSCC) classified into three groups based on human papillomavirus (HPV) 16 DNA presence and p16 expression display different protein expression patterns. STUDY DESIGN: Cross-sectional study. SETTING: A laboratory-based study of patients with OSCC treated at a tertiary care academic medical center. SUBJECTS AND METHODS: Paraffin-embedded OSCC specimens from 77 patients classified into the three-class model (HPV negative, HPV inactive [HPV16+/p16-], and HPV active [HPV16+/p16+]) were queried for the expression of 14 tumor progression proteins using AQUA (HistoRx, New Haven CT). Protein expression between groups was assessed by analysis of variance. Global expression patterns were determined by unsupervised hierarchical clustering. RESULTS: There were significant differences in expression of beta-catenin (P = 0.009), epidermal growth factor receptor (P = 0.009), and vascular endothelial growth factor (P = 0.028) between groups. HPV-active tumors had overexpression of beta-catenin. Hierarchical clustering showed HPV-negative and HPV-inactive tumors displayed association patterns distinct from HPV-active tumors. CONCLUSIONS: Tumors classified by HPV DNA presence and p16 expression have different molecular phenotypes. This is the first demonstration of overexpression of beta-catenin (also found in HPV-caused cervical cancer) in HPV-active OSCC. HPV-active OSCC may share a similar ontogeny to HPV-caused cervical cancer.

Consensus statement of the Hellenic and Cypriot Oesophageal Cancer Study Group on the diagnosis, staging and management of oesophageal cancer.

In spite of recent advances in the diagnosis and management of oesophageal cancer, the overall survival of the disease worldwide remains disappointingly low. In Greece and Cyprus, this may be partly due to a failure of health care providers to implement standardised treatment protocols in clinical practice. Development of clinical practice guidelines was undertaken as a joint project between the Hellenic Society of Medical Oncology (HeSMO) and Gastro-Intestinal Cancer Study Group (GIC-SG) in an effort to provide guidance for Greek and Cypriot clinicians in all aspects of the management of oesophageal cancer. A study group was formed comprising clinicians from different disciplines with a special interest in the management of oesophageal cancer. Following extensive review of the literature, the members of the group met in person and consensus statements were developed, which were later subjected to the Delphi survey process by invited national and international experts. Statements that achieved a rate of voting consensus > 80% were adopted. Those that reached a voting consensus of < 80% were revised or rejected. In total, 46 sentences were developed and subjected to the voting process. Of those, 45 sentences achieved a rate of consensus > 80% during the first voting round. One sentence that did not reach a satisfactory rate of consensus was revised by the members of the study group and subsequently incorporated to the final statement. Forty-six recommendations covering all aspects of the management of oesophageal cancer and concise treatment algorithms are proposed by the Hellenic and Cypriot Oesophageal Cancer Study Group. In particular, centralisation of services, care by multidisciplinary teams and adherence to clinical guidelines are strongly recommended.

Prognostic value of kallikrein-related peptidase 6 protein expression levels in advanced ovarian cancer evaluated by automated quantitative analysis (AQUA).

Kallikrein-related peptidases, a subgroup of the serine protease enzyme family, are considered important prognostic biomarkers in cancer. In the present study, we sought to determine the prognostic value of kallikrein-related peptidase 6 (KLK6) in ovarian cancer using a novel method of compartmentalized in situ protein analysis. A tissue array composed of 150 advanced stage ovarian cancers, uniformly treated with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For evaluation of KLK6 protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis (AQUA). Mean follow-up time of the cohort was 34.35 months. One hundred and thirty-five of 150 cases had sufficient tissue for AQUA analysis. In univariate survival analysis, low tumor KLK6 expression was associated with better outcome for overall survival over 3 years (P = 0.019). There was no association between tumor KLK6 expression and progression-free survival (P = 0.128). In multivariate survival analysis, adjusting for well-characterized prognostic variables, low tumor KLK6 expression level was one of the most significant predictor variable for overall survival (95% confidence interval, 1.19-3.50; P = 0.009). High tumor KLK6 protein expression is associated with inferior patient outcome in ovarian cancer. KLK6 may represent a promising disease biomarker and therapeutic target in ovarian cancer.

Bevacizumab added to the irinotecan and capecitabine combination for advanced colorectal cancer: a well-tolerated, active and convenient regimen.

OBJECTIVES: The literature data regarding bevacizumab (BEV) administered together with capecitabine (CAP) and irinotecan (IRI) in patients with advanced colorectal cancer (CRC) are limited. The safety and efficacy of the addition of BEV to the IRI and CAP (XELIRI) regimen were retrospectively analyzed and reported. PATIENTS AND METHODS: Adult patients 18 years or older with advanced CRC, Eastern Cooperative Oncology Group performance status (ECOG PS) < or =2, exposed to < or =1 chemotherapy (CT) regimen not including IRI or CAP, received BEV 7.5 mg/kg and IRI 220 mg/m2 both on day 1; CAP 1.8 g/m2/d, dl-14. The treatment was repeated every 21 days up to a total of 8 cycles. Responding or stabilized patients were treated with BEV 7.5 mg/m2, administered as maintenance every 21 days until disease progression. RESULTS: Thirty-four patients were treated, the majority (29, 85.3%) in first-line: eighteen (53%) male, 16 (47%) female, and aged 37-83 years (median 69.5). The treatment was moderately tolerated with mainly gastrointestinal complications: hematological, cardiovascular and other toxicities were also recorded, but they were manageable. No treatment-related death was noted. The overall response rate (RR) was 47.1%, while 41.2% of the patients achieved stable disease. Median progression-free survival and overall survival were 8 and 14 months, respectively, with 16% progression-free and 62% alive at 12 months. CONCLUSION: BEV-XELIRI is effective and well tolerated, leading to disease control in a vast majority of patients with advanced CRC.

Concomitant gastric adenocarcinoma and stromal tumor in a woman with polymyalgia rheumatica.

Gastrointestinal stromal tumors (GISTs) are rare neoplasms (1%) of the gastrointestinal tract and to our knowledge only rare cases of synchronous presentation of gastric carcinomas and GISTs are reported in the literature. A 72-year-old female with a simultaneous presentation of gastric adenocarcinoma and GIST is presented. Moreover, due to polymyalgia rheumatica the patient received corticosteroids as treatment for the last 3 years. The concomitant occurrence of these neoplasms may involve common carcinogenic factors and there could be an association with polymyalgia rheumatica either as a paraneoplastic presentation or due to its treatment with corticosteroids.

Advances in molecular, genetic and immune signatures of gastric cancer: Are we ready to apply them in our patients' decision making?

In the last few years we have witnessed a vast expansion of our knowledge regarding the molecular and genetic profile of gastric cancer. The molecular subtypes described have shed light on the pathogenesis of the disease, thus prompting the development of new therapeutic strategies and favoring a more individualized approach for treatment. Most of the clinical trials for so called targeted therapies could be considered, at best, partially successful. In addition, checkpoint inhibitors have recently been added to our armamentarium in later stages of the disease, and combinations with chemotherapy and targeted agents are currently under development. In view of the rapid advances of molecular oncology, a new challenge for the clinical oncologist arises: The appropriate patient selection for each new therapy, which can be made possible only through the implementation of predictive biomarkers in our therapy decision making.

Leptomeningeal metastases originated from esophagogastric junction/gastric cancer: A brief report of two cases.

Leptomeningeal carcinomatosis is a very rare manifestation in patients diagnosed with esophagogastric junction and gastric cancer. Its prognosis is ominous and therapy outcomes are disappointing. Herein, we present two patients; one initially diagnosed with gastric cancer and leptomeningeal carcinomatosis but no other evidence of metastatic disease and the other one initially diagnosed with esophagogastric junction cancer, who recurred solitary with leptomeningeal seedings several years after the initial diagnosis and treatment. Furthermore, a thorough and short review of the literature is carried out.

Her-2 protein expression, cellular localization, and gene amplification in colorectal carcinoma.

This study was sought to evaluate the relationship between Her-2 protein expression, cellular localization, gene amplification, and other clinicopathologic parameters in colorectal carcinomas. Her-2 protein expression and gene amplification were assessed in paraffin sections from 106 primary colorectal adenocarcinoma cases using immunohistochemistry and fluorescence in situ hybridization. Both membranous and cytoplasmic immunostaining was evaluated. The results were correlated with each other and with tumor grade, stage, and overall survival. Membranous and cytoplasmic protein expression was identified in 6 (5.6%) and 13 (12.26%) cases, respectively. Gene amplification was detected in 4 (3.7%) cases. There was a high concordance between membranous protein expression and gene amplification (kappa=0.791). No apparent association with any of the clinicopathologic parameters was identified. Membranous Her-2 protein expression and gene amplification are encountered in a small subset of colorectal carcinomas and are highly concordant events. Cytoplasmic protein expression might be either artifactual or it might represent a cross-reacting protein or a precursor form of the mature protein.

Chromogranin A as a valid marker in oncology: Clinical application or false hopes?

Chromogranin A, due to its primary expression throughout the neuroendocrine system, is a widely accepted biomarker for the assessment of neuro-endocrine tumors. It has been traditionally used in the management of patients with tumors of gastro-enteropancreatic origin. Lately, it has also been implicated in various conditions and diseases, both benign and malignant. However, the paucity of data of adequate strength, as well as its relation with common physiologic conditions and its interaction with commonly prescribed medications, limit its clinical use in only a narrow spectrum. Herein, we present a thorough review to the most frequent conditions where its levels are affected, focusing specifically on its potential use as a prognostic and predictive biomarker in oncology.