James F Fleck, MD, PhD

Advice in Clinical Oncology applying Collective Intelligence

POR
ENG

How Doctors Think

Our methodology emphasizes the cognitive approach as an essential intervention for integrative patient care. Patient has the right to know the natural history of their disease to better qualify shared decision-making. Take some time to explore the suggested texts. You will feel included and actually participating in your care program.

To explain how doctors think, we will use a tutorial. The tutorial is a pedagogical resource used to inform the patient about all steps of cancer care. As you navigate through the tutorial, you and your family will understand how doctors guide your clinical case. Although it is easy to follow and self-explanatory, it is recommended that patients and families share the information with their assistant physicians.

TUTORIAL

History and Physical Exam

• Signs and Symptoms
• Diagnostic Hypothesis
• Complementary Tests
• Multidisciplinary Team
• Critical Evaluation

Pathology

• Materials
• Macroscopy
• Microscopy
• Immunohistochemistry
• Genetic Markers

Imaging and Endoscopy

• Assisting Clinical Examination
• Imaging Tests
• Endoscopy Tests
• Examination Report
• Image Review

Staging

• Extent of Disease
• Selection of Tests
• Histological Grading
• Tumor Markers
• Classifications

Treatment Plan

• Treatment Intention
• Surgery
• Radiotherapy
• Chemotherapy
• Targeted Therapy

Medicine and Evidence

• Standard vs Experimental
• Innovations
• Critical View
• Sources & Levels
• Universal Knowledge

Integrative Model

• Team
• Surgeon
• Pathologist
• Consultations
• Assistant Physician

Second Opinion

• Indication
• Benefit (Patient)
• Benefit (Physician)
• Medical Conference
• Urgency

Global View

• Rare Diseases
• International Consulting
• In-person Evaluation
• Co-responsibility
• Clinical Studies

Emotional Care

• Defense Mechanisms
• Information
• Behavior
• Psychology & Psychiatry
• Scope

Family Dynamics

• Family Role
• Pseudoprotection
• Medical Attitude
• Family Attitude
• Questions

Clinical Research

• Basic Research
• Phase I
• Phase II
• Phase III
• Consent

Guidelines for your clinical care

James F Fleck, MD, PhD

CREMERS 8873 | RQE 25613

Copyright 2024
All Rights Reserved

POR
ENG

James F Fleck, MD, PhD

CREMERS 8873 | RQE 25613

Copyright 2024
All Rights Reserved

POR
ENG

History and Physical Exam

Signs And Symptoms
• The branch of medicine that deals with the signs and symptoms of diseases is called semiology. Signs are objective manifestations observed by the doctor during clinical examination, described, and documented according to well-defined technical criteria. Symptoms are the subjective manifestations of the disease reported by the patient. Cancer manifests itself through a set of signs and symptoms, reflecting the biological behavior of the disease. Unfortunately, there are situations where cancer is asymptomatic, which is why periodic medical consultations are advisable for prevention and early diagnosis.

Diagnostic Hypothesis
• Doctors are trained to recognize symptoms and signs that may lead to a cancer suspicion through history and physical examination. For the most common tumors, there are clinical expression patterns that allow formulating diagnostic hypotheses. Understanding the clinical expression patterns of major tumors is essential for proposing hypotheses. Proposing hypotheses is an indispensable step in the medical consultation.

Complementary Exams
• Complementary exams are selected, indicated, and interpreted with a focus on the diagnostic hypothesis, enabling or ruling out its confirmation. These exams, including clinical laboratory tests, imaging diagnostic methods, endoscopies, and even pathological anatomy, are not absolute, and their validity depends on their adequacy to the clinical expression pattern of the disease. The physician actively and critically seeks to harmonize all these data to achieve diagnostic specificity.

Multidisciplinary Team
• Cancer requires diagnostic precision. This precision depends on the cumulative efforts of multiple professionals. The breadth and complexity of medical knowledge necessitated specialization. Doctors are trained to seek integration in a format called multidisciplinary. The diagnosis results from the combined efforts of doctors with complementary specialties, including clinicians, surgeons, radiologists, and pathologists, among others.

Critical Evaluation
• One of the most important characteristics of medical activity is critical evaluation. The accuracy of cancer diagnosis is greater the more critical the attending physician is. Medicine is not an exact science like mathematics or physics. It is a science of reasoning based on probabilities. The reliability in identifying and classifying cancer is based on the physician’s ability to integrate data from multiple converging diagnostic specialties.

Pathology

Materials
• The materials used for the anatomopathological exam (AP) may come from a biopsy, where only a small fragment of the tumor is sent to the laboratory, or they may correspond to a surgical specimen, where a significant part or the entire organ affected by the tumor is sent to the pathology laboratory. The AP exam generates a report that the pathologist forwards to the attending physician, describing the morphological diagnosis. When the material consists only of fluid aspirated from the tumor or a body cavity, such as pleural or peritoneal fluid, the exam is limited to identifying small cellular clusters and is called cytopathology.

Macroscopy
• This is the part of the anatomopathological exam where the pathologist describes the alterations in the shape of the examined material without the use of optical magnification resources. Macroscopy allows the pathologist to select the most representative areas of the disease, which are sampled and prepared for microscopic examination.

Microscopy
• This is the part of the anatomopathological (AP) exam where the samples selected during macroscopy are prepared for analysis under a microscope, generating the histopathological (HP) diagnosis. This preparation involves fixing the material in paraffin, cutting it with a special instrument called a microtome, staining the material, and placing it between glass slides to allow observation under an optical microscope. In almost all cases, the HP diagnosis is clarified by using a simple and universal staining technique called Hematoxylin-Eosin (HE). In special situations where the HE does not provide a definitive diagnosis, an additional technique called Immunohistochemistry may offer greater definition.

Immunohistochemistry
• This is an extension of the histopathological (HP) exam, where the expression of certain molecular markers can infer part of the biological behavior of the cells. For instance, breast cancer cells expressing estrogen receptors can be identified and quantified through immunohistochemistry. This technique uses monoclonal antibodies with specific binding to the molecular markers being evaluated. Immunohistochemistry increases the degree of precision in cancer diagnosis and can often determine its aggressiveness.

Genetic Markers
• Medicine has advanced significantly in this area. More recently, efforts are focused on identifying the tumor genomic profile, aiming to provide a better understanding of the biological behavior of each malignant disease. The increase in the number of copies of an oncogene, a phenomenon called amplification, as well as the mutation and consequent loss of function of tumor suppressor genes, have been described, leading to a better understanding of malignant transformation. One example is breast cancer, where clinical programs are currently used to assess genetic modifications (Oncotype 21 and MammaPrint). They allow inferences about the tumor’s aggressiveness, guiding better treatment options.

Imaging and Endoscopy

Aiding Physical Examination
• Although physical examination is an essential step in cancer evaluation, there are situations where the tumor can only be detected using devices. These involve endoscopic methods and imaging methods. Both are described in this tutorial section.

Imaging Exams
• Diagnostic imaging methods include X-ray, ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI). These methods allow the visualization of changes in organ shapes. The contrasts used in some of these methods are administered intravenously and enable the enhancement of these changes, further assisting in the diagnosis of the tumor. Additionally, nuclear medicine deals with the functional (metabolic) changes that occur in organs and tissues due to disease. Recently, a very useful method for diagnosing cancer has been introduced, called PET-CT. This method allows identifying the size, shape, and location of the tumor, as well as its metabolic activity. It uses fluorinated glucose as a contrast, which is taken up by metabolically active cells, enhancing the possibility of diagnosing a malignant tumor.

Endoscopy Exams
• These are performed using flexible fiber optic devices that allow visualization and filming of alterations in cavities. The patient is sedated to ensure minimal discomfort during the procedure. In upper gastrointestinal endoscopy, the device is introduced through the mouth, allowing real-time visualization of the esophagus, stomach, and duodenum. In colonoscopy, the device is introduced into the rectum and progresses through the entire large intestine, being a fundamental exam for the prevention and diagnosis of colon and rectal cancer. Bronchoscopy examines the respiratory tree and is one of the main methods used for diagnosing lung cancer. Cystoscopy allows diagnosing bladder cancer. The lesions are photographed, biopsied, and sent to the pathology laboratory.

Exam Report
• Endoscopic and imaging exams always come with a descriptive report, called a laudo, prepared by the physician who performed and interpreted the exam. These reports are accompanied by exam illustrations. In the case of computed tomography, the report is accompanied by the most representative images. For endoscopies, the report is accompanied by films or photographs documenting the described alterations. The reports are prepared by qualified and experienced professionals in their specific technique.

Image Review
• The definitive judgment in cancer diagnosis is made by the attending physician. In addition to the patient’s history and physical examination, the attending physician requires all the information obtained from the imaging, endoscopy, and pathology reports. These reports reveal the technical impression of the professional who interpreted them. For example, in the pathology exam, the report is prepared by a specialized doctor called a pathologist; in the computed tomography exam, the report is prepared by a specialized doctor called a radiologist. These professionals are highly qualified and experienced in making diagnoses. However, even though these exams have already been interpreted by specialized professionals, it is important for the patient to make the materials and images available for review by the attending physician. The reports are technical impressions. The materials and images are facts, belong to the patient, and should always be available for critical review.

Staging

Disease Extent
• This is a concept specially used in malignant diseases. Cancer is usually diagnosed in the primary tumor. However, spreading of cancer cells is the main characteristic of malignant tumors, which occurs predominantly through blood or lymphatic routes. Cancer could be diagnosed at any time during its natural history. The evaluation of the disease extent is called staging. The stage is based on the primary tumor location and size, which is described by the letter T. The stage also includes lymphatic spreading, designated by the letter N and blood metastatic disease, which is represented by the letter M. The combination of the three descriptors creates a classification called TNM. Based on TNM, each cancer type is further categorized from stage I up to stage IV, indicating progressive disease involvement. For each stage there is a specific treatment recommendation and a higher or lower cure rate.

Staging Exams
• Based on the diagnosis, the attending physician decides which tests are necessary to assess the extent of the disease. The exams used for staging include imaging methods such as X-ray, computed tomography (CT) and magnetic resonance imaging (MRI). More recently, PET-CT was included, which assesses both anatomy and metabolic function changes. Eventually, even more invasive methods, such as bone marrow biopsy, are necessary, especially in leukemia and lymphomas. In clinical oncology practice, doctors are very concerned with the precise staging of cancer, selecting the most accurate tests for each specific tumor, based on its biological behavior.

Histologic Grade
• This is also an important concept in cancer staging. During tumorigenesis, normal cells are transformed into cancer cells. Tumor cells can be at different stages of differentiation. Undifferentiated cells tend to be more aggressive, expressing a high proliferative index. The differentiated cells resemble the original form. In microscopy, the chance of identifying the original tissue varies according to the degree of cellular differentiation. The tumor must be classified according to its histological grade. Lower grades are associated with a better prognosis. The best example is the Gleason tumor classification used in prostate cancer. A Gleason 4 tumor is less aggressive than a Gleason 8 tumor. In some tumors, the histological grade has already been incorporated into the TNM classification by adding the G descriptor. You can better understand the prognostic importance of the G descriptor by evaluating staging for soft tissue sarcomas at American Joint Committee on Cancer (AJCC).

Circulating Tumor Markers
• Some solid tumors produce circulating markers, which might give an idea of the extent of the disease. These markers are measured in blood tests. They have little diagnostic value, but have defined implications for prognosis and treatment. An example is the carcinoembryonic antigen (CEA). The CEA is a circulating tumor marker, very useful in the follow-up of colorectal cancer. When it remains high after tumor’s surgical removal, might indicate persistent disease. The CA-125 is widely used for monitoring treatment of ovarian cancer. The CA-125 should normalize after a well-succeeded ovarian cancer treatment. Beta-HCG and alpha-fetoprotein markers are used for monitoring patients with testicular cancer and cure is obtained only after normalizing these markers. The LDH is very important in monitoring lymphomas. The PSA is used in prostate cancer. However, caution is required in its interpretation. A high PSA does not diagnose prostate cancer. PSA is not specific to cancer and might be abnormally elevated in benign prostatic hyperplasia, which consists in a large prostate, but without malignant tumor. However, when cancer is already diagnosed, a rising PSA is directly related to the tumor extension. After surgical treatment of prostate cancer, the PSA should go down to undetected values, indicating that the surgery was radical, which means that the entire prostate tissue was removed. Although tumor markers do not participate directly in the AJCC, often very high values indicate more advanced disease.

Classification
• Staging follows international classification systems, which describe progressive tumor local invasion and systemic spread. The most used are the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC). Staging consists on universal communication criteria with precise implication on cancer prognosis and treatment. Both AJCC and UICC are based on TNM criteria. The descriptor T shows the tumor size and invasion of surrounding tissues or organs. The descriptor N is associated with detection of cancer cells in lymphatic nodes. The descriptor M characterizes the spread through the bloodstream, affecting organs located away from the primary tumor, which is called metastases. For each tumor there are specific criteria that can be found in the international system AJCC, which might be accessed through www.cancerstaging.org. The correct treatment recommendation and its curative or palliative intention are based on cancer stage.

Treatment Plan

Treatment Intention
• This is the first decision that the physician has to face. Unfortunately, not all diseases are curable. Therefore, the intention of treatment should be defined as curative or palliative. Curative treatments have been very well documented in peer review journals and their indications are clear and precise. The physician should describe the treatment plan, discuss results and risks, making sure the understanding and agreement of the patient. Palliative treatments usually require a more complex shared decision-making process. Palliative treatments should combine increasing survival with better quality of life.

Surgery
• When accurately indicated, surgery is still a curative intervention for many benign diseases. For malignant diseases, their role has changed throughout history. Originally, surgery was the only method available to treat cancer. Historically, large resections have been recommended, based on Halsted’s principle of radical tumor removal. Local and regional invasion has been the most important tumor characteristic, limiting its resectability. Today, surgery continues to be an important resource in cancer treatment. Anatomical knowledge continues to be emphasized by doctors, in search of adequate surgical margins. However, the increasing use of combined treatments, including adjuvant chemotherapy and radiotherapy, has allowed more conservative and less traumatic resections.

Radiation
• In malignant diseases, high-energy machines called linear accelerators are used to provide external radiation therapy. The high-energy beams will cause direct damage to the tumor cells DNA and promote the formation of free radicals. The main objective of post-operative radiation therapy is to reduce tumor local relapse. New techniques are progressively evolving in a more precise definition of treated fields and dose fractionation, reducing toxicity without loss in effectiveness. They include three-dimensional conformal radiation therapy (3DRT) and intensity-modulated radiation therapy (IMRT), allowing for a more precise and secure treatment field. Currently, surgeons work in combination with radiation oncologists to produce better results with the least damage.

Systemic Treatment
• It includes chemotherapy and hormone therapy. It is used to treat malignant diseases. Chemotherapy is a combination of cytotoxic drugs acting on rapidly dividing cells. Historically, it was first used with curative intention in the treatment of lymphomas and leukemia. Later, chemotherapy began to be used in the treatment of other solid tumors, looking for systemic disease control. Cancer is often not restricted to the primarily affected organ. Early in tumorigenesis, cancer cells invade lymphatic and blood vessels, leading to distant microscopic deposits called micro-metastases. Unfortunately, micro-metastases are not detectable by imaging methods at cancer diagnosis. In breast cancer, high-risk patients, adequately treated with surgery and radiation therapy, might later have a systemic relapse if not treated with adjuvant chemotherapy. Ironically, the formation of tumor’s lymphatic and blood vessels is an early event in cancer development, often preceding even its clinical detection. The adjuvant chemotherapy concept was developed in order to eradicate all traces of putative residual tumor cells, decreasing the systemic relapse and mortality rate. Based on the same principle, adjuvant hormone therapy acts on micro-metastases, but in more selective hormone-responsive tumors. For instance, it could be used post-operatively to destroy residual breast cancer cells, which express hormone receptors. Chemotherapy and hormone therapy could also be used with neoadjuvant intention. They are used upfront in the treatment of large primary unresectable tumors trying to reduce tumor volume and increase the chance of a complete resection. Both, chemotherapy and hormone therapy might also be used in palliative care. When the disease turns incurable, these methods are judiciously used for relieving symptoms, increasing survival and improving quality of life. Palliative treatments involve difficult technical, ethical, and emotional decisions.

Clever Drugs
• Much of personalized medicine is based on clever drugs’ discovery. It is already possible to identify which patients are most likely to respond, conferring higher treatment specificity. For instance, monoclonal antibodies act on their specific receptors expressed by tumor cells. Some types of breast cancer expressing a receptor known as Her2 could be treated with a monoclonal antibody called trastuzumab. Binding trastuzumab to the Her2 receptor will block the downstream signaling pathway, reducing tumor cell proliferation. Rituximab is another monoclonal antibody that binds to the CD20 receptor of B lymphomas, decreasing cell proliferation. Recently, a great number of monoclonal antibodies have been developed, both for curative and palliative cancer treatment. Additionally, a new class of drugs has been developed acting on the immune checkpoints PD1/PDL1, allowing better recognition of cancer cells by the patient’s immune system.

Medicine and Evidences

Standard Versus Experimental
• Oncology is a medical specialty with systematized knowledge. Primarily, knowledge can be divided into standard and experimental. Standard knowledge is internationally recognized as the best available option at the moment. Experimental knowledge represents a technically and ethically well-founded option but is still under testing and may or may not be useful.

Innovation
• This distinction is crucial because it highlights that experimental is not always better. When talking about innovation, many people interpret it as something fully tested and safe. Unfortunately, in the media, there is no clear criterion for the meaning of new or innovative. Frequently, what is called new, innovative, or a discovery is something still in the testing phase and, therefore, not fully evaluated for its effectiveness or risk. To better guide society medically, new, innovative, or discovery should describe knowledge already fully tested and proven to be better than standard options, replacing older, provenly inferior knowledge methodologically.

Critical Vision
• The specialized physician is the only professional qualified to judge and guide society regarding the standard or experimental classification of a proposed intervention. This is a broad and complex skill, the subject of various international scientific meetings, requiring continuous updating and playing a definitive role in achieving success. Scientific knowledge is always widely disseminated and available. It is up to the physician to critically evaluate it in decision-making.

Sources And Evidence Levels
• Physicians can and should provide the patient and family with the sources where the knowledge is published and allow them to evaluate critically, especially when seeking a second opinion. Doctors know how to categorize levels of evidence for cancer knowledge, which is crucial for safe recommendations. These evidence levels exist in diagnosis, staging, treatment, and prevention scenarios. International classifications categorize evidence levels for scientific knowledge. These are based on the statistical power of the method used to test new knowledge and the degree of recommendation.

Universal Knowledge
• Despite knowledge being sought by patients in interaction with the attending physician, it is universally available in specialized publications. When a researcher describes a new diagnostic or treatment method, they do not own the idea. Instead, they widely publicize it in specialized scientific literature. Researchers are recognized for their authorship and always cited when their data are mentioned. This knowledge may serve as the basis for new ideas, generating a chain reaction of scientific production. Physicians must remain permanently updated. This is possible through continuous reading of specialized journals and participation in international scientific meetings. Whenever there is doubt about the evidence level of a recommendation, the physician should provide references from the scientific literature that methodologically support the guidance given to the patient.

Integrative Model

Care Team
• Oncology is a medical specialty that integrates knowledge and technical skills from multiple professionals. No medical professional can master all the conditions necessary to diagnose and treat cancer. Multidisciplinary behavior improves critical thinking and enhances outcomes. The coordination of multidisciplinary work should be done by the attending physician, who guides the patient through each step of the diagnostic and therapeutic process.

Surgeon
• The interdisciplinary activity of the attending physician begins with a good working relationship with the surgeon. The surgeon’s activity is supported by deep anatomical knowledge and clinical experience in their specific area of expertise. Examples of surgical specialties include neurosurgery, thoracic surgery, urology, gynecology, and gastrointestinal surgery, among many others of equal importance. The surgeon provides essential information for accurately assessing the local and regional extent of the tumor, contributing to staging. The surgeon determines the possibility of completely removing the tumor, a criterion called resectability. Adequate dialogue between the clinician and surgeon aims to obtain the best conditions for the patient to undergo surgical intervention with the least possible risk. This concept is called operability. In evaluating operability, other medical specialties may be consulted, depending on the patient’s clinical needs.

Pathologist
• After the surgical act, another medical professional comes into play. This is the pathologist. They carefully examine and describe the piece removed during surgery. This examination is called anatomopathological. Initially, they perform macroscopic examination, selecting samples from the segments most representative of the disease, embedding them in paraffin, staining them with hematoxylin-eosin, and making microscopic cuts using a device called a microtome. These microscopic cuts are placed on a glass slide and examined under a microscope, allowing visualization of cells and tissues, revealing the diagnosis and classification of the tumor. This phase is called microscopy. The microscopic diagnosis is based on the form of cellular groupings, with defined patterns for each type of tumor.

Consultations
• Comorbidities refer to the set of other diseases occurring in the patient besides cancer. Multiple medical specialties may be consulted depending on the clinical case’s requirements. Severely ill patients may require several professionals. Involving multiple consultations is a responsible medical act and should never be omitted. No professional, regardless of experience or recognition, holds all medical knowledge. For example, if the patient has diabetes, a hormonal disease related to glucose metabolism, consulting a specialized endocrinologist is advisable. A patient with coronary disease requires the involvement of a cardiologist. The number of consultations depends on the number of comorbidities.

Attending Physician
• Working interdisciplinarily is not easy. Harmonizing relationships between professionals is essential for successful outcomes. The attending physician shares decisions while constantly exercising a critical position. The attending physician is responsible for this integrative role. They represent the interface of communication between the patient and family and all other professionals involved in the case. The attending physician is a conductor of an orchestra that must play in tune.

Second Opinion

Indication
• Although oncology knowledge is universal, its application to specific clinical cases depends on individualized critical evaluation. It may happen that the technical impression of a medical professional does not fully meet the patient’s expectations. In such cases, seeking a second opinion is desirable for both the patient and the doctor. While not always the norm, it is a reasonable approach when necessary.

Benefit For The Patient
• Upon receiving a cancer diagnosis, patients often experience significant emotional impact. However, this is also a time that demands a stable and rational approach to decision-making. Such stability depends on accepting the disease and establishing a good doctor-patient relationship. If either of these conditions proves challenging, a second opinion can be beneficial. It provides patients with an opportunity to evaluate recommendations through exposure to another professional’s critical view. It is healthy for the involved medical professionals to exchange opinions about the case. This mature approach seeks consensus and offers security to the patient, allowing them to exercise their right to choose freely. Seeking a second opinion is neither ethically questionable nor a violation of trust but a constructive step towards ensuring proper care.

Benefit For The Physician
• Even when medical recommendations are supported by international evidence levels and published in specialized journals, decisions about specific clinical interventions must always be individualized. Doctors critically evaluate available knowledge and provide recommendations. Patients may express the desire to hear other opinions. A second opinion should not be seen as competition between professionals. Instead, it should combine efforts to achieve the best course of action. A confident physician facilitates and encourages a second opinion, recognizing its potential to strengthen good patient guidance.

Medical Conference
• A medical conference occurs when two or more physicians with complementary specialties discuss a patient’s case. The conference may be requested by the patient or suggested by the physician. The patient must authorize the participation of all professionals involved in the medical conference, as this involves sharing clinical data that belong exclusively to the patient. When the patient cannot provide authorization due to unconsciousness or cognitive impairment, this responsibility passes to the family. During the conference, doctors share information about the patient’s clinical data, review diagnoses, and discuss treatment options. Whenever possible, a consensus is sought. Patients are encouraged to be examined by all physicians participating in the conference. All information exchanged should be documented in a report signed by all participants.

Urgency
• In medicine, there are situations where the urgency of decision-making does not allow for sequential evaluations. A medical conference convenes multiple professionals with complementary skills, streamlining the decision-making process and sharing critical perspectives. In such cases, both patients and physicians benefit from the medical conference.

Global Perspective

Rare Diseases
• Most cancer cases follow standard and universal management. However, there are very specific situations where the attending physician needs to share opinions on an international level. This occurs in rare clinical cases or situations where complexity reaches the limits of knowledge. Physicians dealing with cancer are aware of national and international developments in their specialty. Some medical professionals worldwide focus their practice on a highly specific area. These doctors often work for years with a specific and rare type of cancer, developing concentrated expertise in both clinical and experimental contexts.

International Consultancy
• Very rare cases or those at the frontier of scientific knowledge may require international consultation. This usually involves professionals with concentrated experience in the issue prompting the inquiry. Such experience concentration enables safer judgments, particularly in extreme and severe clinical situations where choosing between standard or experimental treatment is necessary. International consultancy is a current practice and should preferably be conducted in writing to make it official, avoiding confusion with mere opinion exchanges.

In-Person Evaluation
• International cooperation involves shared responsibilities. Patients must understand that exchanging ideas and tests alone may not suffice. Occasionally, travel is necessary. The foreign physician must have the opportunity to examine the patient and request tests within their institution. Opinions given without clinical examination often lack the same level of commitment. This is an extreme pursuit and requires careful evaluation of risks and benefits.

Co-Responsibility
• When international cooperation involves a doctor linked to a hospital, responsibility is additionally shared between the professional and their institution. Specific situations should be considered before the international consultation: medical reports must be translated, materials should be available for evaluation, authorization for transporting biological material may be required, costs and potential health insurance coverage with international reach should be assessed, as well as financial support from the State or assistance from NGOs.

Clinical Trials
• Experimental treatments are available in many research centers worldwide. When the patient is eligible for an experimental treatment, the attending physician should consider the nearest center. If travel is required, the patient’s eligibility for the clinical trial should be evaluated, whenever possible, before the trip.

Emotional Care

Defense Mechanisms
• There is no standard behavior in response to a cancer diagnosis. Defense mechanisms such as denial, aggression, and regression, among others, often emerge. These should not be opposed but respected. In a crisis situation, patients interact with their unconscious and, as a result, choose a defense mechanism to achieve emotional balance.

Information
• All patients know their condition. If they did not, they would not develop defense mechanisms. Medical professionals should strive for open dialogue with the patient, respecting the pace dictated by their emotional state. Physicians must avoid projecting their own anxiety onto the patient. Building trust is a preliminary step. Trust depends not only on technical knowledge about cancer but also on human values. Demonstrating serenity, emotional balance, and a genuine commitment to helping creates the ideal environment for patients to feel supported and free to express their doubts and insecurities.

Behavior
• Cancer can occur at any age. Children respond naturally; they lack preconceived notions of severity and strive to live normally, integrating treatment into their daily activities. Elderly patients develop acceptance over time. Having faced other health issues in the past, they often transfer this coping ability to cancer management, focusing on practical concerns such as autonomy, financial dependency, and family stability. Adults in their prime face unique challenges; cancer disrupts family dynamics and professional responsibilities. These patients seek technical and emotional support from medical professionals, not only for cancer treatment but also for reestablishing life balance. Adolescents often question the diagnosis but are receptive to rational explanations. They require clear communication and respond to factual information but may act impulsively, underestimate the seriousness of treatment, or resist guidance. Adolescents require consistent discipline, attentive care, and emotional modulation.

Psychology And Psychiatry
• Psychological and psychiatric support is only necessary when pre-existing emotional conditions are present or if significant behavioral deviations occur. Anxiety and depression are normal reactions with temporary durations, rarely exceeding three months after diagnosis. Patients often alternate between mild anxiety and depression, seldom requiring medication. Regular follow-ups with the attending physician, maintaining open dialogue, and reinforcing treatment possibilities and recovery prospects are usually sufficient.

Comprehensive Approach
• The core of emotional management lies in the attending physician’s technical competence, perception, sensitivity, and genuine commitment to meeting the patient’s expectations. Illness is part of life, and this circumstance, while undesirable, should be faced with natural resolve. A strong doctor-patient relationship guides appropriate care and decision-making.

Family Dynamics

Role of the Family
• A cancer diagnosis and treatment mobilize the entire family. Anxiety is the most common initial reaction. The family feels vulnerable, faced with a serious illness of uncertain behavior that demands immediate decisions. Patients often rely on their family and share the responsibility of decision-making. This creates a high-risk context, as families lack the technical expertise and emotional neutrality required for such responsibility. A cycle of mutual insecurities may develop. The attending physician must quickly assume an integrative and coordinating role in this crisis.

Pseudoprotection
• Families should not prioritize their anxiety over the patient’s. They should not act as a barrier, preventing open dialogue between the patient and their attending physician. Avoiding such dialogue represents ambivalence and pseudoprotection, delaying emotional balance and complicating the decision-making process.

Medical Approach
• The attending physician, with competence, neutrality, sensitivity, and clear intentions, must organize family dynamics. Physicians make recommendations, provide all necessary elements to support their guidance, and remain available for patient and family inquiries. Families perceive every cancer diagnosis as an urgent matter, and anxiety can arise at any time. The physician must not become unavailable. Whenever the family seeks contact, the physician should be receptive, demonstrate security, and reaffirm their recommendations.

Family Behavior
• Families should encourage patient-physician dialogue. They may actively seek contact with the attending physician, who should inspire confidence in managing the disease and the patient. Physicians and families must achieve effective communication. Families should remain available to assist with all necessary arrangements, taking a proactive role in problem resolution.

Doubts
• Families may seek a second opinion. They can question the physician’s guidance and request to present the case to another professional. However, this requires patient approval. If all parties agree, the second opinion benefits everyone, avoiding insecurity or discomfort.

Clinical Research

Clinical Versus Basic Research
• Clinical research refers to studies involving human participants, aiming to evaluate new treatments, drugs, or medical interventions. Basic research, in contrast, occurs in laboratories and involves cell cultures or animal models (xenotransplants). Basic research focuses on understanding cellular biology, metabolic pathways, gene expression, mechanisms of action, and pharmacokinetics of new drugs. It is an essential precursor to clinical advancements.

Phase I
• Clinical research begins when knowledge gained from basic research supports a well-structured clinical trial project, ethically and technically justified. Phase I studies are the initial step, aiming to evaluate the safety, dosage, bioavailability, metabolism, and excretion of a new drug in humans.

Phase II
• Phase II trials explore the spectrum of cancers for which the new drug may be effective, assessing its side effects and therapeutic potential. A high response rate for a specific type of cancer in Phase II suggests the need for a Phase III trial.

Phase III
• Phase III trials involve comparing the new treatment against the current standard of care. Participants are randomized into two groups: one receives the experimental treatment, and the other undergoes standard treatment. Phase III studies are conducted when Phase II demonstrates superior responses or reduced side effects compared to conventional treatments.

Informed Consent
• Patient eligibility for research programs depends on specific inclusion criteria and requires informed consent. Clinical research projects are conducted exclusively in institutions authorized for experimentation. Ethical committees in these institutions ensure that patient safety and rights are prioritized in every study.