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VASSILIOS BARBOUNIS MD, PhD Pathologist - Oncologist | Piraeus


Generally about cancer

Generally about cancer

Cancer is not just a disease.

By the term cancer is described about 200 different malignant neoplasms, which can be manifested anywhere in the body and which originate from different tissues.

In the US, cancer is now the first cause of death in people under 85, overcoming heart disease. However, the incidence of cancer is also rising in Europe. The pleasure is that in the US mortality from cancer has a downward trend.


What is happening in our country

In the Greek area, the incidence of cancer, as well as at international level, shows an increase in cancer, with mortality decreasing. This is not paradoxical, as technological equipment has evolved so much that cancer prevention and early diagnosis is done at the early stages of the disease, potentially treating this disease.



Cancer is one of the diseases in which periodic preventive testing can make the difference between life and disease. The sooner a cancerous tumor is detected, the more likely it is to be treated effectively, allowing the patient to survive to the natural end.

One in two men and one in three women will be diagnosed with cancer at some point in their lives. 65% of these people will live with their cancer for five years and over, estimated at 70%. These patients are called survivors because they survive with cancer from diagnosis to the end of their life.

More than 25 million people with cancer history live in the world, accounting for 7% of the world's population. Of the survivors, nearly two in ten are women who beat breast cancer, about as many are men with prostate cancer, one out of ten have colon cancer or gynecological cancer.



5-year survival is a statistic - landmark for Oncology. Patients living without recurrence or metastasis of their disease for 5 years after initial diagnosis and treatment are likely to overcome cancer. And the more years they spend, the more likely they are not to come back. Five-year survival for cancer varies according to disease localization

There are no corresponding statistical data in Greece. We arbitrarily believe that Greece currently has about the same survival rates as the European Union and the US.



// 8% to 16% reduction from the decrease in smoking

// 8% of dietary measures, e.g. reducing dietary fat by 25% and doubling the intake of dietary fiber

// 3% with prevention and early diagnosis

// 10% to 26% with innovative treatments

The chances of healing are reduced depending on the stage (they are different at stage II and different in stage III or step IV). Similarly, the average survival in all stages decreases. Thus, for all stages of breast cancer, 5-year survival is 86%, while for all stages of colon cancer 62%.


Many chronic cancer sufferers live a normal life without the disadvantages of their illness. In several cases, the cancer is not completely curable. However, there are other chronic diseases, such as diabetes, for which there is no complete cure, but a permanent treatment is applied. Patients are being treated throughout their lives and lead to an otherwise normal life, even if there are any restrictions.


Breast Cancer


In recent years, significant advances have been made in all areas of diagnosis and treatment of breast cancer. This progress is due to many factors such as advances in technology, advances in molecular biology, the discovery of new molecular pathways associated with carcinogenesis, metastasis and avoidance of apoptosis. As a result of this effort many molecules have been discovered that potentially have the ability to effectively deal with the growth of the cancer cell. The contribution of translation research is decisive in consolidating progress. Progress has been made in other areas such as better knowledge of family and hereditary breast cancer. The recording of mutations, founding or not, the various hereditary syndromes associated with breast cancer. Progress has also been made with the help of molecular biology in terms of molecular classification that gives a fuller picture of the biological behavior of the tumor, as well as the gene signature with which the neoplasm behavior can be predicted and its response to the different forms of treatment.

During the five years that various therapeutic agents have been discovered, others have demonstrated their value while others have shown that they have other therapeutic properties beyond those already known. From the fraction of molecules tested few showed that they had clinical benefit. But all helped to better understand what's happening at the molecular and cellular levels. They also demonstrated the great value of an individualized therapeutic approach compared to a single therapeutic approach.

The overall treatment of breast cancer is multidisciplinary, but the important fact is that progress has been made in all medical specialties dealing with this disease, such as surgery. In recent years, the body's perceptions about the nature of breast cancer have changed, and the size and extent of surgery for local disease control. Technological development also has an impact on the improvement of radiotherapy techniques, resulting in more intensive and effective treatment as well as more effective protection around healthy tissues.
Over the past 10 years, annual mammography has been established as the most valuable method of prevention, as more than 8 randomized trials have shown that it reduces mortality from breast cancer. In the last 5 years, the method of digital mammography has begun to spread, but it has not demonstrated its superiority to analog mammography, possibly excluding women younger than 50 years of age or women with dense breasts. However, it excels in analogy to the possibility of long shelf life and preservation regardless of the existence of films, it can also be analyzed by means of a computer program. The combination of an experienced radiologist and an electronic evaluation system raises the diagnostic accuracy to 95%. The magnetic mammography examination, which has been widely spread over the past five years, has a high sensitivity but lacks a specificity, in addition mammography mammography was established as a necessary complementary test for mammography and clinical examination:
1. in female mutation carriers of the BRCA 1 or 2 or PTEN or P53 genes
2. mutant vectors which have not been genetically engineered
3. in women with a severe family history (> 20% risk of breast cancer)
4. in women with a history of lobular carcinoma in situ and
5. in women who received chest radiotherapy at 10-30 years of age

Additionally, with regard to prevention, the development of the past 5 years has been the increasing recognition of cases of inherited breast cancer (BRCA 1, 2, P53, PTEN mutations, etc.) and the creation of familial cancer units, although there is no recognized framework nor cover the gene control. Criteria for gene control are as follows:
1. Age of invasive breast cancer diagnosis <45 years
2. Bilateral breast cancer
3. Male breast cancer
4. Breast cancer at any age and> 2 relatives of 1st or 2nd degree with already existing breast cancer
5. Breast cancer <50 years old and> 1 relative with breast cancer <50 years old or related to ovarian cancer
The last five years have been characterized by the acceptance and spread of the use of lymph node technique instead of lymphatic cleansing of the armpit in patients with early breast cancer without clinically detectable swollen larynx lymph nodes. This practice was sealed by presenting the mature results of the NSABP-B32 study. This study involved 5611 women with early breast cancer without clinically detectable axillary lymph nodes and subjected to octectomy. Half of the lymph node(s) of the guard(s) were excised, while the rest of the lymph node was also cleared. The two groups did not differ in overall survival, disease free survival, or the number of relapses. The practice of lymph node removal is therefore safe and protects patients from the morbidity of lymph node axillary clearance in patients with early (operable) breast cancer without clinically pronounced infiltrate axillary lymph nodes.


Recently, the results of the ACOZOG Z0011 trial were reported in which 892 early-breast (T1-2) breast cancer patients (T1-2) clinically participated in NO and M0 subjected to ostenectomy and lymph node exclusion, which was found to be positive by hematoxylin-eosin staining. Half of them underwent lingual lymphadenectomy while the rest were not subjected to further surgery. They did not receive axillary radiotherapy while they received supplemental systemic therapy and breast radiotherapy. The two groups of patients did not differ in rates of relapse in the breast or armpit and did not differ in overall disease survival or survival after 6.2 years of follow-up. This study did not complete the predicted number of patients due to a low rate of patient involvement, but concluded that patients with early breast cancer (T1-2) and limited lymph node disease may not benefit from lymphatic cleansing of the armpit.
Thus, since the introduction of breast conservative surgery, the medical community seems to adopt the conservative armpit surgery in patients who meet the criteria of published randomized trials, which results in less morbidity and incomparably better quality of life.
Oncoplastics is a newer method that has been developed to restore the shape and shape of the breast of the patient who has undergone a conservative surgery, that is to say, an octectomy or a quadructomy for removing breast cancer. This is a relatively simple method that is implemented in very few centers worldwide, one of which is in our country. The process is relatively simplified but quite difficult and requires special equipment. In a few words liposuction is performed from a suitable point of the patient and from the 250 cubic centimeters of fat removed eventually a collection of progenitor cells of the adipocytes collected in a syringe and occupying a volume of 5 cubic centimeters is made. Then there is another liposuction from the patient and the volume of fat removed 250 cc which are finally processed and remain about 20 to 25 cubic centimeters of adipocytes. The whole of the cells from the two aspirations are made into a mixture and injected into the area that existed in the breast and which we want to cover. The success of the method is very important and the side effects are virtually nil.
Technological developments have also influenced radiotherapy over the last 5 years. New techniques such as 3D conformal, IMRT (Intensity Modulated Radiation Treatment) and advanced brachytherapy techniques have been developed. The aim of these newer techniques is the reduction of radiotherapy toxicity and more precise, personalized design. The technique of accelerated partial breast irradiation in patients undergoing conservative surgical treatment and having small tumors and up to 3 infiltrating axillary lymph nodes (NSABP-B39 / RTOG-0413) is also under study.
In addition, supplemental axillary radiotherapy was applied over the last 5 years and in patients with 1-3 infiltrated axillary lymph nodes, whereas prior armpit radiotherapy was applied only to patients with> 3 infiltrating lymph nodes. This change was made after studying the subgroups of an earlier study, which showed survival and local area control benefits.
Separate groups of breast cancers bearing particular gene signatures have been identified in recent years. Based on these, several types of breast cancer were clustered in luminal A, B (usually with positive hormone receptors), HER-2 positive (C-erb-B2 oncogene oncogene), basal (usually negative estrogen receptors, progesterone and normal C- erb-B2 - triple negative tumors.
With respect to HER-2 positive breast cancer, following the announcement of results from 3 large studies (BCIRG 006, HERA, NCCTG N9831 / NSABP-B31), trastuzumab (Herceptin ™) is systematically used in the complement therapy of this type of breast cancer preventing half the relapses and increasing the survival of patients with early disease. In addition, over the past 3 years, a younger agent targeting this type of breast cancer at the same receptor but at another site (intracellularly) lapatinib, (tyverb ™) was approved and used in patients who relapse or worsen after trastuzumab. It has recently received pan-European approval for the treatment of postmenopausal patients with hormone-susceptible breast cancer in combination with aromatase inhibitors. Earlier stages of clinical studies have found newer targeting agents that are expected to further improve the treatment of breast cancer bearing HER-2 enhanced or overexpressed.


In terms of hormone-susceptible breast cancer, several complementary hormone therapy studies have been completed in postmenopausal women (ATAC, MA-17, IES, ABCSG / ARNO, TEAM, etc.) which have enhanced the role of aromatase inhibitors in adjuvant treatment of women and their superiority to tamoxifen is now accepted. In addition, a newer antiestrogen, fulvestrant (faslodex ™), was shown in postmenopausal women with metastatic breast cancer as a second-line treatment.
"Triple Negative" breast cancer (negative estrogen and progesterone receptors and normal HER-2) has been identified as a separate class of breast cancer, which often has poor prognosis and is devoid of targeted treatment. The research interest focuses on the development of personalized treatment, and it appears that some of these patients (those carrying the mutation of the opsonoprotective gene BRCA-1), in addition to standard chemotherapy, may benefit from PARP-1 inhibitors (poly-ADP ribose polymerase -1), an enzyme that normally repairs a fragment in a DNA strand.


Angiogenesis is an interesting cancer control tactic. Its goal is to suppress angiogenesis and consequently to the development of breast cancer. In recent years many factors and methods of inhibiting neovascularization have been developed. So far, the most effective agent is the monoclonal antibody bevacizumab (avastin ™). This antibody effectively binds VEGF (vascular endothelial growth factor) by actively inhibiting neovascularization and tumor growth. This drug is combined with all other active drugs and in published studies so far, it effectively increases survival without aggravation of the disease as well as the number of overall objective responses. In breast cancer, excluding bevacizumab, the targeting of tumor neovascularization by other factors has not yielded the expected results.
Positive development was also the improvement in supportive treatment of cancer patients, and aprepitant (Emend ™), a newer neurokinin-1 receptor antagonist, was approved and released, which significantly improved patient tolerance to strong and moderately emetic chemotherapeutic agents.


It also became apparent from studies that Zolentronic acid bisphosphonate administered as a prophylaxis for osteoporosis in early breast cancer patients receiving adjunctive therapy with aromatase inhibitors significantly improved the survival without recurrence of patients who received combination therapy demonstrating that they also had antineoplastic action.
Another development in breast cancer is recognition of the fact that there is a possibility that the phenotype of primary cancer and relapse may differ. Thus, early studies show a change in the phenotype in about 10-20% of cases, either due to tumor dynamics or more accurate diagnosis. Therefore, in cases of relapse and when relapse does not occur soon after initial diagnosis, it is advisable to attempt a second biopsy to give a more accurate therapeutic approach, when feasible.


The greatest development of the past 5 years was the understanding that breast cancer treatment should be personalized. So the design of newer clinical studies includes research into finding biomarkers that predict the expected benefit of a cure. So we hope patients in the years to come receive more targeted, effective and less toxic treatment.


It has been shown that the risk for women to develop breast cancer increases with the early onset of the period. This risk is almost double in women with men less than 12 years of age when compared to those who were younger than 13 years of age. The early age of menstruation is an important risk factor for developing breast cancer for both premenopausal and postmenopausal years. Young women who had an early menstrual cycle have quicker ovarian cycles that during their second decade have higher levels of oestradiol circulating in the blood and lower levels of globulin that binds sex hormones.

Hazard also increases with delayed menopause as it has been established that there is a doubling of the risk for women who still have menstruation and after the age of 55 compared to those whose normal menopause was before the age of 45 years. Artificial menopause appears to protect women from breast cancer. In studies that have been done, women who underwent surgical treatment with hysterectomy and ovariectomy, compared with other women whose ovaries were preserved, found that among those with the ovariectomy before the age of forty years there was a fourfold decrease in cancer growth of the breast. Those who underwent similar surgery and had stopped the period due to this event had significantly better results (ie less breast cancer) for the age of 40 -44 years and similar results for the age of 45 to 55 years. As a result, the earlier menopause occurs, the greater the protection of the individual. These results underline the important role that ovaries have for the development of breast cancer, as their prolonged function increases the risk of developing breast cancer.


In every family, there are some common traits that are inherited from one generation to the next. Less obvious features of eye color, hair or other similarities between parents and their children are some genetic properties that determine the trend of disease development, such as certain types of cancer.
Unfortunately, it is not known to the general public that about 10% of cases of breast and ovarian cancers are inherited - that is, due to a mutant gene transferred from the parent to the child. In fact, cancer is not inherited, but the possibility of its development.
Research evidence suggests that early diagnosis and preventive medicine reduce the risk of developing cancer and saving lives.
The probability of inherited cancer risk is important if the individual: Has been diagnosed with breast cancer before the age of 50 years and / or ovarian cancer regardless of age. If she has close relatives (either mother or father) who were diagnosed with breast cancer before age 50, or who had ovarian cancer regardless of age, or were men with breast cancer, of all ages.
Two specific genes, BRCA1 and BRCA2, play an important role in the prevention of breast and ovarian cancer. Normally, these genes, acting as brakes, stop abnormal cell growth. Sometimes, however, modifications or mutations of these genes occur and lose their normal function. Then cell growth is controlled. Some cellular groups can grow at an uncontrolled rate and can develop cancer.
Each one brings us a copy of each gene - one from the mother and one from the father. In case a parent carries a mutation of BRCA1 or BRCA2, one of his children is likely to carry the mutant gene.
It is important to know that while mutations in the BRCA genes are associated with most breast and ovarian cancers, there are other genetic causes, some well-known, some still to be discovered.

Women with BRCA mutations have:

  • 33-50% chance of developing breast cancer by the age of 50 and 56-87% up to 70 years.
  • 27-44% chance of developing ovarian cancer by 70

Half of the women with inherited risk of developing breast and ovarian cancer inherited the mutant gene from the father and not from their mother. BRCA mutations also increase the risk of developing other types of cancer in both men and women, including the 6% chance of breast cancer in men.
Also, in patients with breast or ovarian cancer, a mutation means a higher risk of developing second cancer.
If there are cases of breast or ovarian cancer in the family, it is important to realize that there are choices. The doctor can help find ways to reduce individual risk by doing the following:

// Monthly self-examination from 18-21
// Annual or 6-month breast examination starting at age 25-35
// Annual mammography and / or magnetic mammography from the age of 25-35

Annual / 6-month transvaginal ultrasound and CA-125 assay starting at age 25-35.
Medicines such as tamoxifen may reduce the risk of breast cancer in some high-risk women.
Contraceptive tablets can significantly reduce the risk of ovarian cancer.
PREVENTIVE SURGERYProphylactic mastectomy can significantly reduce the risk of breast cancer
Preoperative ovariectomy significantly reduces the risk of ovarian cancer as well as breast cancer.



The existence of targeted treatment with the humanized trastuzumab (Herceptin) monoclonal antibody for overexpression of the Her-2 gene has literally changed the natural history of breast cancer, but also the way it has been treated so far in both early and metastatic disease.
The benefit occurs immediately after treatment, in the early years and concerns both non-recurrent and overall patient survival. Patients receiving trastuzumab had 50% fewer relapses than those who did not take the medicine in all studies involving thousands of patients.


The duration of administration of trastuzumab every one or three weeks is one year and can be given either concurrently with chemotherapy or radiotherapy or after the end of adjuvant chemotherapy.
The most significant toxicity of trastuzumab is cardiotoxicity ranging from 1-4%. Cardiotoxicity is transient and very rarely leads to clinical heart failure. For this reason, all patients taking Herceptin should be monitored cardiologically before and during treatment every three months. This treatment has significant financial costs but the clinical benefit is important.
Lapatinib, a small intelligent molecule, has proven to be effective in combination with chemotherapy in metastatic disease.


Based on these significant results, an international study has been launched that aspires to change the prognosis of breast cancer patients expressing HER-2 / NEU receptor cells. In this study called ALTTO, after adjuvant chemotherapy, patients are randomized to receive either Herceptin or Herceptin and Lapatinib. The results of this international multicenter study are awaited with tremendous interest.
The use of anthracycline and taxane based chemotherapy in conjunction with biological agents has significantly increased the survival of breast cancer patients and has significantly reduced deaths from this disease in combination with mammography. Another area where progress has been made is hormone therapy in surgical breast cancer. Newer drugs such as aromatase inhibitors (anastrozole, letrozole, expestane) are safer than tamoxifen and much more effective for postmenopausal patients, while tamoxifen and gonadotrophin analogues (GN-RH) are still used for premenopausal women ).
In conclusion, thanks to the ongoing research and the discovery of new therapeutic factors, the future for breast cancer patients is extremely promising and promising.



Metastatic breast cancer is a difficult disease to fight, and chemotherapy is the right choice for most patients. Various drugs are combined and administered in programs of 2 or 3 drugs. Their responses range from 35 to 50% when given as monotherapy in patients who have not been previously exposed to chemotherapy. The duration of their efficacy is approximately 8 to 12 months.

Taxanes are a group of active chemotherapeutic agents against breast cancer and have proven their value compared to both paclitaxel and docetaxel with all classic chemotherapy programs. They have been administered in combination therapy but also as monotherapy. In all comparative studies, they produced similar or better results than previous drugs. Paclitaxel combinations with anthracyclines give responses in the range of 60-65%, while the time to worsening of disease ranges from 7.5 to 8 months. Total survival is from 20 to 24 months. In addition to the aforementioned factors, there are other younger ones, such as capecitabine, which has good safety features and satisfactory responses, particularly in combination with taxanes where the responses amount to 42% and time to worsening to 6.1 months. Taxanes can also be combined with trastuzumab (Herceptin) with very good results. Other drugs with significant efficacy are gemcitabine and navelbin. Finally, older agents such as doxorubicin are administered in a new liposomal formulation. Doxorubicin molecules are incorporated into lipids resulting in the same efficacy but clearly less toxicity.

Recently, the arsenal of metastatic breast cancer has been provided with biological therapies such as monoclonal antibodies against the HER-2 receptor and against the vascular endothelial growth factor VEGF. These factors provide a benefit to the survival of these patients with acceptable toxicity. Administration of trastuzumab (Herceptin) together with chemotherapy has improved overall survival of patients while co-administration of chemotherapy and bevacizumab (Avastin) has provided patients with a doubling of response time. Tyverb has been shown to be safe and very effective at the clinical level as a treatment for metastatic breast cancer.
Its action is different from herceptin, as it is a small molecule, acts intracellularly and has the significant advantage of oral administration. Very important was the observation that fewer new brain metastases occurred in the group receiving lapatinib (Tyverb) as the drug, as a small molecule, passes the blood-brain barrier. Although metastatic breast cancer remains essentially a dysentery disease, however, advances in chemotherapy and breast cancer therapies have succeeded in improving prognosis and doubling the survival of these patients.

Its action is different from herceptin, as it is a small molecule, acts intracellularly and has the significant advantage of oral administration. Very important was the observation that fewer new brain metastases occurred in the group receiving lapatinib (Tyverb) as the drug, as a small molecule, passes the blood-brain barrier. Although metastatic breast cancer remains essentially a dysentery disease, however, advances in chemotherapy and breast cancer therapies have succeeded in improving prognosis and doubling the survival of these patients.
In conclusion, thanks to the ongoing research and the discovery of new therapeutic factors, the future for breast cancer patients is extremely promising and promising.


Colon Cancer

Colorectal cancer is one of the most common cancers in the world (the fourth most commonly diagnosed malignancy in the US and the second cause of malignant death).
Early diagnosis and treatment at the earliest possible stage, as well as for all forms of malignancy, are critical to curing and avoiding further problems in the future. This is accomplished by early attendance at the clinician with the onset of symptoms and preventative examinations in the context of asymptomatic control. a basic examination in this procedure is colonoscopy performed by a gastroenterologist.


Asymptomatic prophylaxis for colorectal cancer in cases of moderate risk (without a family history of polyposis or inherited non-polydipstic colon cancer - such cases are closely monitored from an early age) begins with a basic colonoscopy from the age of 50, repeated at 10 years and supplemented with annual microscopic examination of faeces, flexible sigmoidoscopy at 5 years with or without faecal examination at 3 years. In cases where polyps are found, the precancerous lesions are examined, removed and monitored at the discretion of the specific gastroenterologist.

The common symptoms of colorectal cancer are:
bleeding from the rectum, usually during stools, stomach upset (constipation, diarrhea or constipation and diarrhea), abdominal pain, pre-existing underlying microbial anemia (loss of hematocrit), anorexia - weight loss, tenderness and loss of mucus with stool. In initiating and continuing any of the above symptoms, the patient should refer to a gastroenterologist and perform blood tests and colonoscopy. The loss of blood should not be attributed unclearly to "hemorrhoids" either by the doctor or by the patient, without a colonoscopy, because in this case the delay in diagnosis may be fatal to the patient.
Therefore, preventative asymptomatic control and early recognition of symptoms and attendance to the specialist are vital and can save lives as there is the medical potential in our country to diagnose and treat this common and difficult condition.


Colorectal cancer is one of the most common cancers in the world (the fourth most commonly diagnosed malignancy in the US and the second cause of malignant death).Early diagnosis and treatment at the earliest possible stage, as well as for all forms of malignancy, are critical to curing and avoiding further problems in the future. This is accomplished by early attendance at the clinician with the onset of symptoms and preventative examinations in the context of asymptomatic control. A basic examination in this procedure is colonoscopy performed by a gastroenterologist.

Asymptomatic prophylaxis for colorectal cancer in cases of moderate risk (without a family history of polyposis or inherited non-polydipstic colon cancer - these cases being closely monitored from an early age) begins with a basic colonoscopy from the age of 50, repeated in 10 year and supplemented with annual faecal microscopic examination or flexible sigmoidoscopy at 5 years with or without faecal examination at 3 years. In cases where polyps or precancerous lesions are found, these are examined, removed and monitored at the discretion of the specific gastroenterologist.
Therefore, preventative asymptomatic control and early recognition of symptoms and attendance to the specialist are vital and can save lives as there is the medical potential in our country to diagnose and treat this common and difficult condition.


Lung Cancer

Chemoprevention for lung cancer

More than two-thirds of lung cancer patients appear at the time of diagnosis at advanced stages IIIb and IV. The main risk factor is smoking, which is responsible for 90% of cases in men and 75-80% for women. Apart from tobacco, other environmental, family and dietary factors seem to be involved in the pathogenesis of the disease.
Studies that have been made in airway lung cancer patients have shown that lesions such as dysplasia and hyperplasia with aneuploidy are observed extensively throughout the epithelium and are not related to solid tumor but apparently develop independently. Together with other studies in head and neck tumors, the findings support the view that the entire respiratory system undergoes genetic disorders after long-term exposure to carcinogens.

The histological classification of squamous cell carcinoma in the bronchial epithelium is:
1 = normal,
2 = hyperplasia,
3 = metaplasia,
4 = low grade dysplasia,
5 = high grade dysplasia,
6 = atypical adenomatous hyperplasia,
7 = CIS
8 = invasive cancer.
Stages 2, 3, 4 are considered reversible lesions of the epithelium and not precancerous.

Epithelial carcinogenesis is divided into three phases.The initial-initiation, the promotion-promotion phase and the progress-progression phase. At the first stage the genetic lesions occur in the DNA, in the second stage the phenotypic abnormalities appear from the disturbed genetic cell and in the third stage genetic and phenotypic abnormalities occur complicated and at a fast pace. Thus, cancer is a complex phenomenon with multiple processes at cellular and molecular level and is characterized by a prolonged period between the initial phase of carcinogenesis and the occurrence of cancer.

The most important measure of prevention is smoking cessation, although former smokers have an increased risk of lung cancer compared to non-smokers. Several studies have shown that eating vegetables and fruits has been associated with a reduced risk of developing lung cancer. This has led to the assumption that some elements can be used as chemopreventive agents for lung cancer. The 5-year survival rate after diagnosis of the disease is less than 15%. The high mortality rate has imposed a different approach to controlling this disease, such as chemoprophylaxis and early diagnosis.

Chemoprevention, which was first used by Spom in 1976, is to prevent the development of epithelial neoplasms by administering natural forms of vitamin A and its synthetic analogues, called retinoids. Chemoprevention is useful in reducing the incidence of carcinoma in well-defined groups of at-risk individuals but also in the general population. With chemoprevention, substances that inhibit or prevent carcinogenicity are used and aim at therapeutic intervention in early stages of carcinogenicity before the onset of invasive cancer. Retinoids have been studied in the past in the past and are potential prophylaxis agents, and molecular pharmacological targets such as EGFR and COX2 receptor blockers are currently being tested. Retinoids are natural or synthetic derivatives of vitamin A. Carotenoids are a family of polyene complexes rich in fruits and vegetables, and some of these are precursors to retinoids. Retinoids are potential regulators of gene and cellular expression through the core receptors. Two classes of retinoid receptors (RAR receptors and RXR receptors) have been identified with at least three subtypes for each class (α, β, γ respectively). These receptors, after being attached to the retinoid molecule via a binding molecule, activate the target genes and thereby regulate proliferation, apoptosis and cell death.

Carotenoids (BC) have been studied extensively as chemopreventive agents, as epidemiological data have shown that their use is associated with a reduction in the incidence of lung cancer. Experimental models and clinical studies have shown that carotenoids can be agents for treating or preventing cancer. One of these studies is the successful treatment of paraneoplastic lesions such as oral leukoplakia, dysplasia of the cervix and xeroderma pigmentosum.

Early diagnosis of lung cancer, as many studies have shown, contributes to better outcome of lung cancer. The discovery of intermediate carcinogenicity markers, the use of fluorobronchoscopy by laser, sputum cytology and the use of low-dose helical CT scan have increased diagnostic sensitivity. These indicators to be useful should be considered as potentially reversible. Possible such markers are microscopic changes in the bronchial epithelium or even more specific, cytogenetic and molecular changes of the epithelium. The research focuses on intraepithelial neoplasia, a precancerous condition already known in colon adenomas and cervical epithelium. On a pathological basis, in order to consider the observations in the bronchial epithelium, the metaphase index method, a quantitative method that detects the degree of metaplasia in a number of intrabronchial biopsies, was introduced. The degree of metaplasia / dysplasia in the bronchial mucosa appears to be more dependent on the test population than on the pathologist's judgment. Transformation as a histologic marker of bronchial epithelium is not a satisfactory option because it has been shown to exhibit automatic reversibility, as does dysplasia. Bronchial epithelium dysplasia is the best index of reversibility at this time and the morphological criteria characterizing it have been thoroughly analyzed in the renewed WHO edition. However, further studies are needed to prove the predictive value of changes in bronchial epithelium in lung cancer. Even today very little is known about the reasons for these changes. Other biological markers tested by immunohistochemistry include Ki67, MCM2, p53, EGFR, CD31, HER2, pMAP and pAKT. These markers express the reproductive capacity, apoptosis and cell angiogenesis. And here we need continuous research to document them as intermediate markers in clinical evaluation. Research on the detection and clinical application of new markers continues based on the potential of modern technology, such as the application of the microchip gen array molecular method. The exact identification of the groups high risk is crucial for the application of chemopreventive clinical trials and for the implementation of a screening test for lung cancer.

High risk groups are defined based on age, degree of tobacco use, exposure to asbestos, pulmonary function, exposure to radioactivity, coexistence of COPD, degree of atypia in sputum cytology and family history. The risk of developing lung carcinoma in relation to the degree of pulmonary emphysema in helical CT was last determined.

Many studies have shown that there is a clear correlation between the amount of exposure to tobacco expressed in the Pack Years Index (PY = number of cigarettes per day x number of years consumed) and the development of lung cancer. However, today there are strong indications that cancer growth is more related to smoking time than to the amount of cigarettes. In terms of the risk of developing lung cancer among smokers with 20 PY, it is 11.59 when they smoke 20-29 cigarettes a day for 20-29 years, but it increases to 29.66 when smoking is 10-19 cigarettes a day but for 40 years. Thus, the use of PR is redefined and it is suggested that patients be included in the high risk group when the average tobacco consumption is 30 PY with at least 20 cigarettes per day.

Van Klaeveren et al suggest that the high-risk group include patients with the reported age of smoking regardless of age as well as those who underwent surgical resection for stage I non-small cell lung cancer.

The definition of intermediate indicators, as mentioned earlier, is also very important for the selection of high-risk groups. As shown by a large study that collected non-smoker bronchial biopsies, histological and molecular lesions in the non-smoker bronchial epithelium were far more rare than those smokers whose degree of lesion increased with tobacco consumption. Genetic factors have a significant impact and the finding of gene predisposing indicators is at the forefront of laboratory research.

In a study by the University of Colorado, bronchial dysplasia was considered as a risk indicator in high risk groups (> 30PY, COPD), and it was found that this group of 55% experienced spleen in a high degree of dysplasia. Using moderate or severe dysplasia as a risk indicator, the degree of risk for developing lung cancer increased to 3,242 and by adding hypermethylation of DNA to 7 genes in dysplasia, the degree of risk increased to 10.2 (Hirsch ASCO 2003, personal communication). This study continues in a larger population of individuals.

Finally, with the use of helical CT, new possibilities appear to identify subduced damage in the respiratory system. The biological substrate of these lesions is not elucidated, possibly related to epithelial damage characterized as atypical adenomatous hyperplasia (AAD). A major study is currently being conducted in M.D. Anderson in which high-risk individuals undergo a screening test using low-dose spiral CT in order to study the use of helical CT as a method of controlling high-risk groups.

Studies on gene mutations as predictors of lung adenocarcinoma development and their follow-up during chemopreventive treatment are underway.

Chemoprevention types
1. Primary chemoprophylaxis for the prevention of lung carcinoma in healthy high-risk individuals, such as current and former smokers, especially when they have pathological spirometry.
2. Secondary chemoprevention aiming at restoring or disrupting the progression of precancerous lesions (intraepithelial neoplasia, leukoplakia, bronchial mucosa dysplasia and atypical adenomatous hyperplasia). Genomic, proteomic and molecular markers are considered essential.
3. Tertiary chemoprevention, to prevent the occurrence of subcutaneous or second primary tumors in patients, with concurrent control of carcinogenicity markers, such as Ki-67.
Primary studies are Phase III studies. None of these studies showed any positive effect on cancer prophylaxis. In contrast, evidence suggests that current and former smokers who received β-carotenoids had a higher risk for lung cancer (cancer risk and mortality for the ATBC and CARET study: 18% and 8%, 28% and 17%, respectively).

In the secondary category, the studies are Phase IIb and smokers treated with metaplasia or sputum atypia. The evidence did not show the prophylactic effect of retinoids. Quitting smoking is the only factor of reversibility of neoplastic lesions, while the combination of discontinuation and use of retinoids further reduced sputum metallisation.

Finally, in the tertiary category, there are three Phase III studies available. Pastorino's study confirmed the positive results of clinical studies done in head and neck tumors using retinoids. The other two studies did not show the same positive result.

Regarding the adverse effects from the use of these retinoids, a statistically significant appearance of yellowing of the skin was observed with β-carotenoids and dryness of the skin and mucous membranes from their use. Other statistically significant adverse reactions from the use of retinoids were the onset of arthralgia, vomiting, indigestion and hypertriglyceridemia.


Estimated Treatment Cost


In the US, the cost of cancer as a percentage of total health costs is 5-7%. Its variation was Health cost as a percentage of gross national product
// 1970: 7%
// 1990:12%
// 1997:14%
// 2030:26% (calculated)

Health spending in the US will increase this decade by 2010 faster than the overall economy and by 2019 nearly 20 cents for every dollar spent in the US will go to health. Health trends in Europe are upward, averaging 9% of GDP, 10% in Greece, and 15% in the US. Public expenditure on oncology is comparatively low. They rank third in 2009 after cardiovascular diseases and central nervous system diseases. The increase in health expenditure, especially in the last decade in developed countries, is mainly due to:

  • the aging of the population and the resulting increase in demand,
  • in the prevalence of chronic diseases requiring long-term treatments,
  • the new medical and pharmaceutical technology that is more expensive and the increased demands and expectations of citizens for more and better medical care. the increase in health expenditure will continue as these trends continue to prevail. How much they will grow is not something given, despite the OECD's doubling of their doubling by 2050.

Investigating the cost of treating cancer
An integral part of modern clinical studies is the assessment of the economic parameters of new therapies. In the US, the NCC has formulated relevant procedures and guidelines. In daily medical practice, unnecessary variability in treatment options results in great economic wastage. A solution to the problem can be given by standardization of practice in medical care, ie the formulation and implementation of clinical guidelines based on scientific evidence bis (evidence based) .The clinical guidelines are product specific meetings (experts meetings), to formulate consensus statements (consensus statements). On Oncology, the following therapeutic recommendations and guidelines are particularly important.
// National Comprehensive Cancer Network (NCCN)
// American Society of Clinical Oncology (ASCO)
// National Cancer Institute (NCI)
// European Society of Medical Oncology (ESMO)


Neoplasia records
Today, they exist in all European Union countries based on the population covering all or part of the national populations except Greece.


Prevention & Diagnosis


Lung cancer is the leading cause of cancer death for both men and women. The number of people dying from lung cancer each year has increased over the past 25 years and is greater than the number of people dying from breast, prostate and colorectal cancer cumulatively. Several factors increase the risk of lung cancer, but the most important risk factor is smoking.

PREVENTION ----Smoking is responsible for almost 90% of cases of lung cancer. Exposure to certain substances, such as asbestos, exposure to passive smoking and various environmental factors such as radon, have also been linked to the development of lung cancer. The best way to avoid lung cancer is to not smoke. Some smokers believe that once they have smoked for a long time, they do little to stop smoking. However, studies have shown that smokers who stop significantly reduce the risk of lung cancer compared to those who continue to smoke. Smokers who have interrupted for more than 15 years have a 80-90% reduction in lung cancer risk compared to people who continue to smoke.

PLURAL CONTROL (screening) ---- ΤScreening is a way of checking to identify a disease in its early stages before the patient experiences symptoms. To be recommended for a particular disease, it should be clear that it can identify patients suffering from the disease in the early stages and that this discovery can reduce the number of patients dying from this disease.
Some screening tests have improved patient survival by detecting early-stage cancer and reducing the risk of death by giving early treatment. Some examples are the Pap smear test for the detection of cervical cancer in women and colonoscopy for the detection of colorectal cancer in over 50s. These tests are now routine tests in developed countries.
Lung cancer screening with low-dose CT has been shown to reduce the risk of death for people over the age of 55 who have a long history of smoking. However, screening is not as important as stopping smoking, as interruption will reduce the risk of other cancers and cardiovascular diseases.

LUNG CANCER SCREENING  ---- There have been studies to determine if lung cancer screening makes sense. In these studies, smokers (who are most at risk) are divided into groups. Some groups are screened, while others are not. These groups are then monitored for many years and data are collected on how many patients from each group are diagnosed with lung cancer, how cancer was treated, how much patients survived the treatment and how many patients died from the disease (mortality).

Low-dose CT scan ---- A large randomized study (the National Lung Screening Trial or NLST) in the United States compared the benefits of low-dose CT scanning compared to simple chest X-ray in smokers (who have smoked at least 30 packet years and continue to smoke or have stopped smoking for the last 15 years). Compared to simple chest X-ray, low-dose CT scan reduced the risk of death from lung cancer by 20% and the overall risk of death by about 7%. However, nearly a quarter of patients who had been screened for three years had pathological effects and more than 95% of these results were "false positives," meaning they did not represent cancer.
"False positive" results require re-screening tests, such as x-rays or, sometimes, biopsies. Therefore, the re-screening tests pose risks, such as radiation exposure, as well as possible biopsy complications. So, screening obviously has drawbacks.

Annual screening with low-dose CT is now recommended by many scientific organizations for smokers or former smokers (who have interrupted within the last 15 years) with a long history of smoking. More specifically, annual screening is proposed for patients with good health who are 55 to 80 years of age, have a smoking history of at least 30 packet years, and if they are ex-smokers who have stopped smoking in the past 15 years.

Chest X-ray ---- Although many health care providers are an annual chest X-ray for smokers, the studies have not shown any benefit, so this practice is not recommended. In a large randomized study (the National Lung Screening Trial or NLST) mentioned above, comparing simple chest X-ray to CT scan for lung cancer screening, only axial showed a reduced risk of death. Thus, the current guidelines do not recommend screening with chest X-ray.

Sputum cytology examinations ---- Some studies have examined the value of patient sputum analysis for finding cancer cells and early detection of lung cancer. So far, no benefit has been found with this approach. Additional studies using new technologies for sputum examination are in progress.

ΡΕΤ scan ---- researchers are looking at a range of other tools in an effort to help early localization of lung cancer patients. PET scan (positron emission tomography, which uses a small amount of radioactivity to provide a detailed view of an organ function) has been used in conjunction with CT / CT. However, it includes a higher dose of radiation compared to only axial and no benefit for screening purposes has been demonstrated.

Other studies ---- bronchoscopy, bronchoscopy, respiration analysis, or blood tests for cancer markers are currently not used in screening, but can be tested in future studies.


Psychological Support


Undoubtedly, the word cancer causes fear, since it has been identified with death and for most people it is considered identical to it. And only this finding, in itself, can impose and justify the existence of the psychologist in any oncology clinic. Now, and in this context, we are not dealing with any psychological problems that anyone can bring in from the past, but with the psychological burden it accepts, even the healthiest, psychopathologically, patient, because of its presence disease and the possible battle it will take against it.

More specifically, the science of psychology offers the necessary tools for a fuller understanding of human existence and the problems it faces. The two predominant theoretical trends of psychoanalysis and behavioral analysis if viewed, not based on their differences and the distances separating them, but in addition, can provide useful information and valuable practices both for understanding and for offering further psychological support to patients with neoplasia.

Thus, for example, Kubler Ross's exemplary work on patients facing death, and in particular her theory of the five stages of sadness, helps us to understand phenomena like denial, the fact that the sufferer or the close his family environment denies the existence of illness, the anger that either remains indeterminate and diffused or is specified and usually accompanies the all-natural question "why me?", the negotiation of desire to put our lives under new conditions under our apparent control, and depression to the lack of everyday activities and communication and consequent isolation and loneliness. Recognizing that all of these reactions are only a normal consequence that precedes time from cancer acceptance helps us address the breadth of the spectrum of different patient behaviors in the light of scientific acceptance and empathy.

On the other hand, the science of behavioral analysis has long overcome the behavioral stimulus / reaction pattern and recognizing that most of our behavior, in addition to being non-reflexive, depends on its direct interaction with environment, provides the necessary knowledge so that the changes that occur in the immediate environment can be managed in a more painless way. For example, knowing that our behavior, for the most part, is shaped by the long-term amplification and eradication functions, that is, we tend to repeat, in similar contexts, behaviors that have previously been enhanced (an amplifier may be any stimulus such as bravo, hugs and signs of friendship, money, gifts, food, etc.), and that we tend to avoid repeating behaviors that in the past, in similar contexts, were not reinforced we can, in a direct way, reinforce or not enhance behavioral patterns depending on whether they respond to tendency, torque and desire for life.

Knowing that you suffer from a disease that, for the most part, can cause death, is a new condition, an unpleasant change, and both adaptation and acceptance are processes in which the presence of the psychologist is consistently important the recognition of the comforting finding that we are not alone on this difficult road. In addition to the oncologist's medical presence, as well as the patient's family and friendly environment, professional assistance based on the principles of psychology science can effectively help to improve the conditions and quality of life of the patient and his / her family.