Cancer in Children PDF

Charlotte Eikaas 2023/24 CANCER IN CHILDREN EPIDEMIOLOGY DIAGNOSTIC STEPS 2nd leading cause of death in children (#1 = accidents) History: special emphasis on family history Bimodal peak: 15 y/old...

Charlotte Eikaas 2023/24 CANCER IN CHILDREN EPIDEMIOLOGY DIAGNOSTIC STEPS 2nd leading cause of death in children (#1 = accidents) History: special emphasis on family history Bimodal peak: 15 y/old Physical exam In general, ALL is the most common, except in those Lab test: biochemical, hormones, immunologic, genetic 50% are infratentorial, 40% supratentorial, 5% spinal cord Rhabdomyosarcoma: MC (70%): good prognosis in stage I/II; Low grade astrocytomas orbital type has worst prognosis 50% of brain tumors in children- MC subtype Locations: H&N > parameningeal > extremities MC location: cerebellum > hemispheric > midbrain Best prognosis: botryoid, spindle cell RMS Young children → pilocytic astrocytoma Intermediate prognosis: embryonal Older children → fibrillary astrocytoma- bening-ish Poor prognosis: alveolar, undiff, anaplastic 10 year overall survival – 80% Other STS Medulloblastoma Neurogenic sarcoma: 10% 85% seen in patients pelvis Familial Wilms tumor: FWT1/2 mutation Labs: ↑catecholamines in urine (90%) Denys-Drash syndrome: WT1 mutation; Wilm’s tumor 60-70% have distant metastasis at diagnosis- liver, BM, subcutaneous Beckwith-Wiedemann syndrome: multiple genes; Wilms tumor, Stage I + II → surgery + adjuvant chemo hepatoblastoma, neuroblastoma, pancreatoblastoma Stage III → induction chemo + surgery and RT Tuberous sclerosis: TSC1/2 mutation; subependymal giant cell Metastasis to skin → blueberry muffin sign astrocytoma OTHERWISE NOTEWORTHY Children have higher likelihood of measurable side affects after cancer treatment; stunted growth is normal and there’s high risk of RT-related skeletal injury. Cranial RT before 5 y/old may lower IQ 35  ONCOLOGY SYMPTOMATOLOGY AND CLASSIFICATION CANCER DIAGNOSIS: Noplasms can mimic benign inflammatory conditions and vice versa. anamnesis Histologic proof of malignancy is the clinical examination cornerstone of diagnosis and treatment laboratory analyses (!!) imaging histopathological examination IMPORTANT 1) histopathology BEFORE 2) staging Exception when treatment can be initiated w.o. TREATMENT 3) biomarkers histopathological confirmation = palliative care Cancer symptoms according to frequency: Cancer symptoms FOR TEST: know which biomarkers are predictive vs. ✗ General → unexplained weight loss, fevers, prognostic (!!) fatigue, pain and loss of apetite ★ HER2 positive = neg prognostic factor but positive ✗ Related to the tumor site predictive factor ✗ Related to the treatment ★ Oropharyngeal tumors which are p16 positive → positive predictive factor (for radiotherapy) 1 SYSTEMIC EFFECTS OF TUMORS CACHEXIA - Very common in advanced disease - sarcopenia, malaise and progressive weakness (!) CACHEXIA ANEMIA Progressive weakness, malaise, Additional causes of anemia: anorexia and muscle wasting Rapid tumor proliferation which uses up existing associated with the presence of a stores of folate (macrocytic anemia) malignancy Autoimmune hemolytic anemia frequently May pre-date diagnosis of associated with chronic lymphocytic leukemia malignancy Myelosuppression of bone marrow after TNF-a released by tumor cells and treatment (use of iron) macrophages have been implicated No universally effective therapeutic modalities appear to be able to reverse cachexia COAGULATION ABNORMALITIES Common in pancreatic cancer Thrombocytosis Thrombocytopenia LEUKOERYTHROBLASTIC PERIPHERAL DIC BLOOD Hypercoagulable state Immature myeloid cells and nucleated RBCs due to bone marrow invasion by tumor - usually in - Increased fibrinogen, factors V and VIII breast cancer. with subsequent venous thrombosis - Potential for pulmonary embolization INFECTIONS ★ Trousseau’s sign Due to impared humoral or cell-mediated immunity - Migratory superficial thrombophlebitis Opportunistic infections; common in - Often accompanies pancreatic cancer malignancy Fever unassociated with infections - Hodgkin’s disease - Renal adenocarcinoma - Osteogenic sarcomas FEVER Often seen in advanced disease Almost all patients will have fever at some time, particularly if the cancer affects the PAIN ⚡ immune system Usually is a symptom of advanced disease Less often fever may be an early sign of May be an early sign (e.g. bone, testicular) cancer 2 PARANEOPLASTIC SYNDROMES Production of hormones or hormone-like substances by a tumor, causing The only way to cure remote symtoms not directly connected to tumor invasion. paraneoplastic syndromes is to treat Occurs in 10% of patients with malignant neoplasms. the cause = treat the May be the first indication of the presence of an underlying cancer. malignancy (!) HYPERCALCEMIA ENDOCRINOPATHIES MOST COMMON paraneoplastic syndrome Cushing Syndrome Overtly symptomatic hypercalcemia is more likely due to Hyperadrenal corticism malignancy than hyperparathyroidism Most common paraneoplastic ★ Pulmonary squamous cell carcinoma, breast, renal, endocrinopathy ovarian carcinoma, adult T- cell leukemia/lymphoma Excessive production of ACTH, ACTH-like Mechanisms peptides – 50% of patients have pulmonary - Secretion of PTH-like substances (PTHrP)- normally small cell cancer produced in low quantities by several tissues ★ Pulmonary small cell cancer, pancreatic (keratinocytes, breast, bone, muscle, ovary) carcinoma, neural tumors - IL-1, TGF-a, TNF-a, dihydroxy vitamin D - Non paraneoplastic- bone metastasis or primary bone LAMBERT-EATON SYNDROME tumors with lysis of bone- osteosarcoma, multiple Myasthenia gravis-like features (muscle myeloma, prostate, breast cancer weakness) ★ Most commonly associated with small cell DERMATOLOGIC SYNDROMES carcinoma of the lung (SCLL) Acanthosis nigricans Differs from myasthenia: Skin; grey- black itching patches of - Muscle strength increases hyperkeratosis usually in skin folds with exercise Fingerprint enhancement - There is poor response to Tensilon (edrophonium) ★ Gastric, lung, uterine carcinoma HYPERTROPHIC OSTEOARTHROPATHY Dermatomyositis Periosteal new bone formation, fingers and Asthenia, pain and hypertrophy of toes proximal muscles Distal ends of long bones, metatarsals, Purple lesions on the face and metacarpals, proximal phalanges palms Arthritis adjacent joints Gottron nodules- over small joints Clubbing of digits Patients need cancer screening for ★ Bronchogenic carcinoma 3 years after diagnosis ★ Ovarian cancer, lymphomas, lung, gastric cancer 3 HIPPOCRATIC FINGERS = DRUMSTICK FINGERS = WTACH-GLASS NAILS CANCER-SPECIFIC SYNDROMES / SYMPTOMS ★ ”GOOD FOR TEST” ★ LUNG CANCER Symptoms related to tumor site: cough General symptoms: hemoptysis weight loss pain in the chest loss of apetite dyspnea anemia dysphagia fever recurrent pneumonia paraneoplastic syndromes (hypertrophic osteoarthropathy, Cushing’s syndrome, pleural effusion hyperpigmentation, gynecomastia, Lambert-Eaton hoarseness (paralysis of the recurrent syndrome, encephalopathy etc.) laryngeal nerve) paralysis of the phrenic nerve (one-sided elevation of the diaphragm in chest X-ray) SMALL CELL LUNG CANCER (symptoms) Primary tumor: cough, dyspnea, wheezing, hemoptysis, chest pain and post-obstructive pneumonitis Metastases: regional → SVCS, hoarseness, dysphagia & distant → bone pain, CNS symptoms (headache, diplopia) SYNDROMES related to lung cancer 1) Superiro vena cava syndrome 2) Pancoast’s syndrome 3) Horner’s syndrome 80% due to lung cancer Symptoms associated with superior = Ipsilateral ptosis, miosis, pulmonary sulcus tumor anhidrosis, enophthalmos Indication for immediate oncological treatment Shoulder and arm pain Infiltration of cervical sympathetic nerves Symptoms: Dyspnea, headache, Horner’s syndrome swelling of the face, arms and the Weakness and atrophy of hand upper chest, skin reddness, venous muscles distention in the neck, upper chest and arms, cough, symptoms of ★ Causes: Non- small cell lung cerebral edema cancer & other neoplasms (thoracic, hematologic) – Infectious diseases 4  BREAST CANCER Related to the primary tumor Related to the enlarged axillary lymph nodes Related to distant metastasis Related tor treatment Symptoms related to the primary tumor: - tumor - deformation of the nipple - skin deformation, erythema, edema = peau d’orange - inflmmatory cancer - Paget’s disease - automastectomy Symptoms related to metastatic lymph nodes: tumor arm edema ulceration HEAD & NECK CANCER LYMPHOMAS pain General symptoms = ”B-symptoms” tumor, ulceration ✴ weight loss (>10%/6 mo.) disturbed breathing and food intake ✴ night sweats dysarthria ✴ fever (> 38 degrees) hoarseness Skin pruritus is not included in the B-symptoms (!) limited mobility/immobilisation of tongue face deformation, stiff nose Symptoms related to tumor location sore ears lymphadenopathy (axilla, neck, groins) epistaxis dyspnea - mediastinal lymphadenopathy 5 CERVICAL CANCER GASTRIC CANCER Early symptoms: Symptoms: postcoital bleeding Similar to those seen in non- malignant diseases: discharge - Pain in the upper abdomen Late symptoms: - Loss of apetite bleeding KRUKENBERG TUMOR = - Nausea, vomiting metastatic lump on the ovary pain - Melena (anemia!) swelling of limbs - Weight loss dysuric symptoms, hydronephrosis - Chainges in digestion (feeling full after small meal, infiltration of the lower part of the digestive tract indigestion) Advanced disease: - Tumor, ascites, hepatomegaly, jaundice COLORECTAL CANCER General symptoms: Symptoms related to localisation abdominal pain Rectum, left side of Right side of colon blood in stool colon bleeding abdominal pain change in frequency: chronic constipation, diarrhea change in bowel habits: fatigue constipation/diarrhea anemia change in size of the stool abdominal pain tumor in abdomen weight loss ileus change in bowel habits intestinal occlusion → ileus ileus perforation of the colon/rectum VIRCHOW’S NODE BLUMER’S SHELF SISTER MARY JOSEPH SIGN = metastatic left supraclavicular = metastatic tumor of the puch of = palpable nodule bulging into lymph node, indicating cancer in the Douglas, felt in rectal examination umbilicus (toward skin surface), abdomen caused by metastasis of abdominal/pelivc cancer 6 BRAIN TUMORS metastatic/primary FOCAL SYMPTOMS: SYMPTOMS OF RAISED ICP: paresis headache aphasia vomiting vision disturbances blurred vision seizures quantitative impairment of consciousness cranial nerve palsy seizures Personality disorders, mood disorders and psychosis (!) TNM STAGING SYSTEM Staging decides the intention of treatment (!) ★ Modifiers c: clinical stage, meaning the stage has been determined by clinical examination and imaging p: pathologic stage, meaning the stage has been confirmed via histology or cytology y: indicates the TNM stage has been determined after completion of neoadjuvant therpay For example: ypT3N1M0 rectal cancer is one that has been resected after neoadjuvant therapy, with histology showing invasion through the full thickness of the rectal wall and involvement of 1-3 regional lymph nodes. ★ Stage Each tumor type has a stage grouping, which is the categorisation of malignancies into stages from I to IV. A single stage grouping may have multiple TNM stages assigned within it, generally those with a similar prognosis. For example: In lung cancer for example, T4N0M0, T3-4N1M0 and T1-3N2M0 all lie within Stage IIIA.7 Female reproductive system cancer (cervix, uterus, ovarry, vagina) The FIGO (International Federation of Gynaecology and Obstetrics) system is used. The stage is determined by features such as degree of invasion, ureteric obstruction, lymphadenopathy and peritoneal seeding. It ranges from Stage I to IV. Lymphoma The Ann Arbor classification is used to describe how many lymph node regions are involved and whether the nodes are on one or both sides of the diaphragm. The presence or absence of “B symptoms” (night sweats, fevers, weight loss of >10%) is an important prognostic factor and this has been incorporated into the staging system as a suffix after the stage descriptor. For example, Stage IIIB Hodgkin’s lymphoma indicates the presence of B symptoms and involvement of nodal stations on both sides of the diaphragm. Small cell lung cancer This does utilise TNM staging, however more commonly it is simply divided into limited and extensive disease, based on whether it is intrathoracic and can be encompassed within a radiation portal. Other (non-staging) parameters Disease parameters which play a very important role in determining treatment and prognosis. The important variables differ depending on the tumour site but include: tumor grade hormone receptor status specific serum markers (eg. PSA, LDH, hCG, AFP) chromosomal abnormalities (eg. 1p19q co-del in oligodendroglioma) Clarl Level (melanoma !!) Performance status and weight loss are independent prognostic factors, and a patient with apparent early stage disease but a poor performance status or significant, unexplained weight loss is unlikely to tolerate, or be cured by aggressive treatment (!!) 8 ECOG / WHO / ZUBROD SCORE 0 - Asymptomatic (Fully active, able to carry on all predisease activities without restriction) 1 - Symptomatic but completely ambulatory (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature. For example, light housework, office work) 2 - Symptomatic, 50% in bed, but not bedbound (Capable of only limited self-care, confined to bed or chair 50% or more of waking hours) 4 - Bedbound (Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair) 5 - Death KARNOFSKY SCORING 100 - Normal; no complaints; no evidence of disease. 90 - Able to carry on normal activity; minor signs or symptoms of disease. 80 - Normal activity with effort; some signs or symptoms of disease. 70 - Cares for self; unable to carry on normal activity or to do active work. 60 - Requires occasional assistance, but is able to care for most of their personal needs. 50 - Requires considerable assistance and frequent medical care. 40 - Disabled;requires special care and assistance. 30 - Severelydisabled; hospital admission is indicated although death not imminent. 20 - Very sick; hospital admission necessary; active supportive treatment necessary. 10 - Moribund; fatal processes progressing rapidly. 0 - Dead 9 CANCER EPIDEMIOLOGY, PREVENTION AND EARLY DETECTION Incidence = number of new cases arising in a given period in specified population (100 000 persons) Prevalence = number of persons in a defined population who have been diagnosed with that type of cancer, and who are still alive at a given point in time (100 000 persons) Mortality = number of deaths occuring in a given period in a specified population (100 000 persons) Lethality = mortality/incidence ratio Sources of epidemiologic data in oncology: (1) cancer registries, and (2) death certificates GLOBOCAN is the source used for cancer data (at least in the power point) Higher incidence rate of cancer in developed countries due to high age, but lower mortality compared to developing countries. Explained by higher age in these countries and better medical care. Estimated cancer incidence/mortality in the world in 2012: MEN WOMEN Causes of increased cancer mortality: ๏ Aging population ๏ Better diagnosis ๏ More reliable statistics ๏ Changes in life style and environmental factors 11 Cancer incidence/mortality/5-year prevalence in Europe Cancer incidence/mortality/5-year prevalence in SWEDEN 12 CANCER PREVENTION Primary = reduction of exposure to carcinogenic factors Secondary = early detection and treatment of precancerous lesions CANCER DETECTION Clinically apparent disease - noticed by patient Asymptomatic disease - detected at routine physical exmination or detected by mass screening programs SCREENING PROGRAMS Include populations without symptoms of particular disease Main aim of screening Aim at decreasing mortality caused by a particular disease, by means = decrease mortality of its earlier detection Including large populations: mass screening Effective screening methods: ★ CERVIX - cervical cytology ★ BREAST - mammography ★ COLORECTAL - fecal occult blood CERVICAL CANCER: One of the most common cancers in developing countries (about 25% of all female cancers) WOMEN from 25 yrs of age should participate Less common in industrialised populations due to mass screening in cervical screening (!) programmes Efficacy of screening using a cervical smear (Pap) test performed every 3 years HPV test more sensitive (!) Most common to start screening at age 21 (in Poland 25, in Sweden 23) - The best age to start pap-smear is 5 years after the first sexual intercorse Pap-smear every 3 yrs (!!) HPV test every 5 yrs Pap-smear every 3 years. Co-testing (HPV testing + PAP smear) 30-65 yrs of age. HPV testing is not recommended before 30 yrs of age because at a younger age it can give many false positives - young women can have HPV infection but the immune system can handle the infection and does not have to progress to cancer (would not be present later). 13 Screening guidelines for cervical cancer - Americal Cancer Society (2012) Among the changes: the American Cancer Society no longer recommends that women get a Pap test every year There are 2 types of tests used for cervical cancer screening. - The Pap test can find early cell changes and treat them before they become cancer. The Pap test can also find cervical cancer early, when it’s easier to treat. - The HPV (human papilloma virus) test finds certain infections that can lead to cell changes and cancer. HPV infections are very common, and most go away by themselves and don’t cause these problems. The HPV test may be used along with a Pap test, or to help doctors decide how to treat women who have an abnormal Pap test. Women who have had their uterus and cervix removed in a hysterectomy and have no history of cervical cancer or pre-cancer should not be screened. Women who have had the HPV vaccine should still follow the screening recommendations for their age group. Women who are at high risk for cervical cancer may need to be screened more often. Women at high risk might include those with HIV infection, organ transplant, or exposure to the drug DES. In short, the American Cancer Society no longer recommends that women get a Pap test every year, because it generally takes much longer than that, 10 to 20 years, for cervical cancer to develop and overly frequent screening could lead to procedures that are not needed. BREAST CANCER: Mammography screening Mammography can detect breast tumors at clinically undetectable stage Women > 50 yrs of age Mammography screening reduces breast cancer mortality by 25% in women should paricipate in over 50 yrs of age mammography The value of screening women aged under 50 yrs of age is uncertain screening Mammography - reduces mortality by 1/3. COLORECTAL CANCER: Colorectal cancer is one of the most common malignancies in developed Men and women > 50 countries yrs of age should participate in Annual or biennial screening with faecal occult blood testing reduces colorectal cancer mortality by 16-27% colorectal cancer screening Colonoscopy is more effective and can be performed every 10 years Lung cnacer screening: low dose CT performed annualy in heavy smokers aged 55-74 yrs, reduces mortality, BUT cannot be an alternative for smoking cessation. 14  Screening methods of unknown value Screening methods that are ineffective ! prostate - PSA lung cancer - chest X-ray stomach - H.pylori testing and/or radiographic breast - self-examination examination testis - self-examination ovary - Ca125 and/or USG neuroblastoma - urinary homovalinic acid breast - mammography < 50 yrs skin - examination of moles oral - examination of mouth LENGTH-TIME BIAS Length-time bias = is a form of selection bias, a statistical distortion of results that can lead to incorrect conclusions about the data. LEAD-TIME BIAS Lead-time bias = is the length of time between the detection of a disease (usually based on new, experimental criteria) and its usual clinical presentation and diagnosis (based on traditional criteria). It is the time between early diagnosis with screening and the time in which diagnosis would have been made without screening. It is an important factor when evaluating the effectiveness of a specific test. 15