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.

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.

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.

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.

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.

Clinical practice guidelines for the management of metastatic colorectal cancer: a consensus statement of the Hellenic Society of Medical Oncologists (HeSMO).

There is discrepancy and failure to adhere to current international guidelines for the management of metastatic colorectal cancer (CRC) in hospitals in Greece and Cyprus. The aim of the present document is to provide a consensus on the multidisciplinary management of metastastic CRC, considering both special characteristics of our Healthcare System and international guidelines. Following discussion and online communication among the members of an executive team chosen by the Hellenic Society of Medical Oncology (HeSMO), a consensus for metastastic CRC disease was developed. Statements were subjected to the Delphi methodology on two voting rounds by invited multidisciplinary international experts on CRC. Statements reaching level of agreement by ≥80% were considered as having achieved large consensus, whereas statements reaching 60-80% moderate consensus. One hundred and nine statements were developed. Ninety experts voted for those statements. The median rate of abstain per statement was 18.5% (range: 0-54%). In the end of the process, all statements achieved a large consensus. The importance of centralization, care by a multidisciplinary team, adherence to guidelines, and personalization is emphasized. R0 resection is the only intervention that may offer substantial improvement in the oncological outcomes.

Follicle-Stimulating Hormone Receptor (FSHR): A Promising Tool in Oncology?

The cellular pathway of follicle-stimulating hormone (FSH) and its receptor (FSHR) is typically involved in reproduction in mammals. In humans, the FSHR is normally found in cells of the testis and the ovary, while it is scarcely expressed in other normal tissues. The expression of FSH/FSHR is studied in prostate, thyroid, and ovarian cancer tissues. Recently, the expression of FSHR was uniformly documented in malignant vascular endothelial cells from different tumor types, while in normal or inflammatory tissues its expression was scarce, suggesting a potential role of a pan-receptor in cancer. Subsequent studies have attempted to verify this unique specificity of this molecule and further define its features in malignant microenvironments but have had conflicting results, mostly because of differing techniques and immaturity of antibodies. Still, the lack of FSHR expression in most non-cancerous cells, in contrast to its specific correlation with the malignant tissue microenvironment, implies a potential role as both a diagnostic and a therapeutic tool. FSHR might also have a very specific role in malignancies, such as angiogenic and/or growth factor malignancies, but this is yet to be validated. Moreover, the expression of FSHR in endothelial malignant cells could have a predictive impact on disease progression, especially in relation to therapies targeting the tumor vasculature. In this review we look deep into the physiology of the FSH/FSHR pathway and evaluate the potential of FSHR as a predictive and prognostic tool in oncology.

Validity of Adjuvant! Online in older patients with stage III colon cancer based on 2967 patients from the ACCENT database.

BACKGROUND: Adjuvant! Online is a tool used for clinical decision making in patients with early stage colon cancer. As details of the tool's construction are not published, the ability of Adjuvant! Online to accurately predict outcomes for older patients (age 70+) with node positive colon cancer receiving adjuvant chemotherapy is unclear. METHODS: Individual data from older patients with stage III colon cancer who enrolled into multiple trials within the ACCENT database were entered into the Adjuvant! Online program to obtain predicted probabilities of 5-year overall survival (OS) and recurrence-free survival (RFS). Median predictions were compared with known rates. As co-morbidities were not known for ACCENT patients, but required for calculator entry, patients were assumed to have either "minor" or "average for age" co-morbidities. RESULTS: 2967 older patients from 10 randomized studies were included. When "minor" co-morbidities were assumed, the median predicted 5-year OS rate of 64% nearly matched the actual rate of 65%; when "average for age" co-morbidities were assumed, the median prediction dropped to 58%, outside the CI for the actual rate. On the other hand, assuming "minor" co-morbidities gave a median 5-year RFS prediction of 62%, outside the 95% CI for the actual rate of 58%, while assuming "average for age" co-morbidities yielded a better median prediction of 57%. CONCLUSION: Adjuvant! Online is reasonably accurate overall for predicting outcomes in older trial patients with stage III colon cancer, though accuracy may differ between 5-year RFS and 5-year OS predictions when a fixed degree of co-morbidities is assumed.

Clinical practice guidelines for the surgical treatment of rectal cancer: a consensus statement of the Hellenic Society of Medical Oncologists (HeSMO).

In rectal cancer management, accurate staging by magnetic resonance imaging, neo-adjuvant treatment with the use of radiotherapy, and total mesorectal excision have resulted in remarkable improvement in the oncological outcomes. However, there is substantial discrepancy in the therapeutic approach and failure to adhere to international guidelines among different Greek-Cypriot hospitals. The present guidelines aim to aid the multidisciplinary management of rectal cancer, considering both the local special characteristics of our healthcare system and the international relevant agreements (ESMO, EURECCA). Following background discussion and online communication sessions for feedback among the members of an executive team, a consensus rectal cancer management was obtained. Statements were subjected to the Delphi methodology voting system on two rounds to achieve further consensus by invited multidisciplinary international experts on colorectal cancer. Statements were considered of high, moderate or low consensus if they were voted by ≥80%, 60-80%, or <60%, respectively; those obtaining a low consensus level after both voting rounds were rejected. One hundred and two statements were developed and voted by 100 experts. The mean rate of abstention per statement was 12.5% (range: 2-45%). In the end of the process, all statements achieved a high consensus. Guidelines and algorithms of diagnosis and treatment were proposed. The importance of centralization, care by a multidisciplinary team, adherence to guidelines, and personalization is emphasized.

Clinical practice guidelines for the surgical management of colon cancer: a consensus statement of the Hellenic and Cypriot Colorectal Cancer Study Group by the HeSMO.

Despite considerable improvement in the management of colon cancer, there is a great deal of variation in the outcomes among European countries, and in particular among different hospital centers in Greece and Cyprus. Discrepancy in the approach strategies and lack of adherence to guidelines for the management of colon cancer may explain the situation. The aim was to elaborate a consensus on the multidisciplinary management of colon cancer, based on European guidelines (ESMO and EURECCA), and also taking into account local special characteristics of our healthcare system. Following discussion and online communication among members of an executive team, a consensus was developed. Statements entered the Delphi voting system on two rounds to achieve consensus by multidisciplinary international experts. Statements with an agreement rate of ≥80% achieved a large consensus, while those with an agreement rate of 60-80% a moderate consensus. Statements achieving an agreement of <60% after both rounds were rejected and not presented. Sixty statements on the management of colon cancer were subjected to the Delphi methodology. Voting experts were 109. The median rate of abstain per statement was 10% (range: 0-41%). In the end of the voting process, all statements achieved a consensus by more than 80% of the experts. A consensus on the management of colon cancer was developed by applying the Delphi methodology. Guidelines are proposed along with algorithms of diagnosis and treatment. The importance of centralization, care by a multidisciplinary team, and adherence to guidelines is emphasized.

Adjuvant chemotherapy for colon cancer: a consensus statement of the Hellenic and Cypriot Colorectal Cancer Study Group by the HeSMO.

Colorectal cancer remains a major cause of cancer mortality in the Western world both in men and women. In this manuscript a concise overview and recommendations on adjuvant chemotherapy in colon cancer are presented. An executive team from the Hellenic Society of Medical Oncology was assigned to develop a consensus statement and guidelines on the adjuvant treatment of colon cancer. Fourteen statements on adjuvant treatment were subjected to the Delphi methodology. Voting experts were 68. All statements achieved a rate of consensus above than 80% (>87%) and none revised and entered to a second round of voting. Three and 8 of them achieved a 100 and an over than 90% consensus, respectively. These statements describe evaluations of therapies in clinical practice. They could be considered as general guidelines based on best available evidence for assistance in treatment decision-making. Furthermore, they serve to identify questions and targets for further research and the settings in which investigational therapy could be considered.

Adjuvant Chemoradiation Therapy in Gastric Cancer: Critically Reviewing the Past and Visualizing the Next Step Forward.

Gastric cancer remains one of the most common malignancies worldwide. Despite the significant advances in surgical treatment and multimodality strategies, prognosis has modestly improved over the last two decades. Locoregional relapse remains one of the main issues and the combined chemoradiation treatment seems to be one of the preferred approaches. However, more than ten years after the hallmark INT-0116 trial, minimal progress has been made both in terms of effectiveness and toxicity. Moreover, new regimens added to combined therapy failed to prove favourable results. Herein, we attempt a thorough literature review comparing pros and cons of all relative studies and potential bias, targeting well-designed future approaches.

The mutational spectrum of Lynch syndrome in cyprus.

Lynch syndrome is the most common form of hereditary colorectal cancer and is caused by germline mutations in the mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2. Mutation carriers have an increased lifetime risk of developing colorectal cancer as well as other extracolonic tumours. The aim of the current study was to evaluate the frequency and distribution of mutations in the MLH1, MSH2 and MSH6 genes within a cohort of Cypriot families that fulfilled the revised Bethesda guidelines. The study cohort included 77 patients who fulfilled at least one of the revised Bethesda guidelines. Mutational analysis revealed the presence of 4 pathogenic mutations, 3 in the MLH1 gene and 1 in the MSH2 gene, in 5 unrelated individuals. It is noted that out of the 4 pathogenic mutations detected, one is novel (c.1610delG in exon 14 of the MLH1) and has been detected for the first time in the Cypriot population. Overall, the pathogenic mutation detection rate in our patient cohort was 7%. This percentage is relatively low but could be explained by the fact that the sole criterion for genetic screening was compliance to the revised Bethesda guidelines. Larger numbers of Lynch syndrome families and screening of the two additional predisposition genes, PMS2 and EPCAM, are needed in order to decipher the full spectrum of mutations associated with Lynch syndrome predisposition in Cyprus.

Targeting the HER2 receptor in metastatic breast cancer.

The advent of targeted therapies has revolutionized the treatment of certain types of cancer. Identification of molecular targets on cancer cells has led to the design of novel drugs, which either used as single agents or in combination with chemotherapy, has prolonged survival in metastatic disease, or contributed to curative treatment in the adjuvant setting. A literature review was conducted to identify and present current knowledge on the molecular function of the HER2 receptor, its role in the pathogenesis of breast cancer and anti-HER2 targeted drugs in use or under development. Many molecular targets have been identified in breast cancer, with the HER family of receptors being the ones most extensively studied. Trastuzumab and lapatinib target the HER2 receptor and are approved drugs for the treatment of metastatic breast cancer. Several other targeted agents, including T-DM1, pertuzumab, neratinib, afatinib and ertumaxomab, are currently being tested in vivo as well as in clinical studies. The use of targeted therapies in metastatic breast cancer has improved prognosis, increased survival and dramatically changed the way we treat breast cancer patients today.