Lung Cancer Overview - 2023/24 PDF

Charlotte Eikaas 2023/24 LUNG CANCER EPIDEMIOLOGY DIAGNOSIS MOST DEADLY CANCER: cause of 1/3rd of cancer deaths- Peripheral tumor: transthoracic fine needle biopsy → more than breast + pro...

Charlotte Eikaas 2023/24 LUNG CANCER EPIDEMIOLOGY DIAGNOSIS MOST DEADLY CANCER: cause of 1/3rd of cancer deaths- Peripheral tumor: transthoracic fine needle biopsy → more than breast + prostate + colon cancer combined fiberoscopy +/- transbronchial biopsy → thoracotomy In women: increasing incidence AND mortality Central tumor: fiberoscopy (bronchoscopy) +/- transbronchial biopsy → transthoracic biopsy → thoracotomy Step 2- determine if limited or extensive: CT abdomen + chest, RISK FACTORS & ETIOLOGY mediastinoscopy, bone scintigraphy, EBUS/EUS biopsy, esophageal - -endobronchial pleural/pericardial biopsy (in effusion), PET/CT during curative therapy, SMOKING- causes 90% of cases; passive smoking also brain MRI (SCLC or if symptomatic) counts (15% increased risk of death). 1 pack/day →25x risk; after quitting risk is normalized after 15 years Staging of SCLC: limited to one hemithorax = limited; spread beyond Occupational carcinogens, Radon, air pollution one hemithorax = extensive disease SUBTYPES TREATMENT NSCLC- 85% of cases: slower and more contained growth; low- NSCLC: surgery is usually go-to, unless cancer is disseminated, which it moderate sensitivity to chemo- better to operate is at point of discovery in 60% func. 113 INS Mo-mtenia for thoracic Surgery + Adequate Lung ↑ , , Adenocarcinoma (40%): via atypical adenomatous Surgery: stage I-IIIA; more effective in lower stages hyperplasia to CIS; usually peripherally located. Lowest RT: stage I-IIIB; more effective in higher stages; best in T3!! correlation with smoking (10%) Chemo: stage II-IV; more effective in higher stages SCC (30%): via squamous metaplasia to dysplasia to CIS; Combined modality: in stage I-II, pre-op + post-op chemo/RT usually centrally located Inoperable stage III N+ NSCLC: radical concurrent chemo- Large cell carcinoma (10%) radiotherapy + consolidation with Durvalumab (PD-1-I) Targeted therapy: for AC- EGFR-I, ALK-I SCLC- 15% of cases: usually centrally located; rapid growth and Hemoptysis → radiotherapy dissemination, high sensitivity to chemo SCLC: chemo (Cisplatin + Etoposide) + thoracic RT + prophylactic cranial irradiation; RT prolongs local control and survival in limited disease PRESENTATION PROGRESSION & PROGNOSIS Associated with local growth: chronic cough (MC!), hemoptysis, dyspnea, recurrent pneumonia/bronchitis, hoarseness, wheezing, 90% of patients will eventually die from the cancer dysphagia, swelling of face/neck, pain in chest, shoulder or back NSCLC: total 5YS 10-15% (better if operable) SCLC: total 5YS 5-8% (20% if limited) Associated with distant metastases: bone pain (ribs, spine), pathologic fractures, compression symptoms (SVC syndrome, Metastasis: brain, liver, adrenals and bones Pancoast tumor), lymphadenopathy, upper abdominal pain, OTHERWISE NOTEWORTHY headaches, dizziness Frequent complications of LC seen on imaging: cavities, bronchial General: weight loss, fever, fatigue, weakness, anorexia obturations, atelectasis, bronchiectasis, pleural effusions, tumor Paraneoplastic syndromes: SCLC is MC cause; Cushing’s, necrosis with abscess, empyema, mediastinal involvement hypercalcemia (SCC!), SIADH, carcinoid syndrome, neuropathies, Pancoast tumor: LC located in apical lobe of the lung, compressing encephalopathies, Lambert-Eaton, polymyositis, hypertrophic surroundings- risk of Horner syndrome, pain in arm and shoulder, osteoarthropathy (AC!), thromboembolism, DIC, anemia, weakness and atrophy of hand muscles leukocytosis, thrombocytosis, hypertrichosis, dermatomyositis 8  Charlotte Eikaas 2023/24 PLEURAL CANCER- MALIGNANT PLEURAL MESOTHELIOMA EPIDEMIOLOGY DIAGNOSIS Rare, but increasing incidence History- exposure to asbestos MC PRIMARY pleural malignancy (metastasis is more X-ray: initial imaging, shows thickening of pleura and fluid common overall) CT: gives detailed image Average age 60 y/old PET: to look for metastasis M>>>F (70-80% men) In case of presenting with pleural effusion → thoracocentesis- fluid can show cancer cells RISK FACTORS & ETIOLOGY Biopsy- definite diagnosis Asbestos exposure- causes diffuse pleural fibrosis; TREATMENT note that exposure is more likely to cause lung cancer, Early disease: surgery +/- RT but is essentially the only cause of pleural Disseminated: palliative chemo (poor results) mesothelioma Symptomatic treatment Risk also increases in family members of those exposed to asbestos PROGRESSION & PROGNOSIS PRESENTATION Long latency-period (20-40y) Chest pain- 70% Usually diagnosed too late- low curability Dyspnea- 60% Fever, sweating, fatigue- 33% each Loss of appetite- 24% Pleural effusion- often recurrent 9  Charlotte Eikaas 2023/24 HEMATOLOGIC CANCER- NON-HODGKIN’S LYMPHOMA EPIDEMIOLOGY DIAGNOSIS 7th most common cancer; 4-3% Excisional biopsy (whole node) More common than HL (60% VS 40%) Clinical staging Mainly affects older adults History + PE RISK FACTORS & ETIOLOGY Chest RTG, CT abdomen + chest (+ pelvis if positive abdominal/ inguinal nodes) Depends on subtype ↓ BM biopsy and CSF examination Other: laparotomy + PET scintigraphy SUBTYPES Ann Arbor: I = single nodal region; II = 2 or more regions on same side of diaphragm; III = 2 ore more on different sides of DLBCL: MC NHL, aggressive. AA 60, but occur in all diaphragm; IV= disseminated ages. Overexpression of BCL6. Either sporadic, or arising from other lymphoma; can occur in any tissue A= no B-symptoms; B = with B-symptoms Follicular lymphoma: MC indolent one, AA 60, F>M. Overexpression of BCL2. Only lymphoma which is TREATMENT graded Aggressive: 30% standard chemo + Rituximab Burkitt lymphoma: very aggressive, but curable. Advanced low-intermediate grade: incurable, but Usually extranodal; may be endemic, sporadic or HIV- chemo, radiation and/or immunotherapy may prolong associated. MC NHL in children. C-MYC translocation. life Sometimes EBV-associated. Mantle-cell lymphoma PROGRESSION & PROGNOSIS Cutaneous T-cell lymphoma- mycosis fungoides. mostly Prognosis depends on subtype; aggressive lymphomas # 75010s CNS lymphoma: usually in deep structures of frontal/ occipital can be cured, indolent ones cannot, but one can live lobe; ependymal infiltration in 75%; NO calcification or with them bleeding May progress to leukemic phase - > MC in stomach MALT- -> related ↳ to treat with he pyloring. Ab Bad prognostic factors: age >60, poor performance status, elevated LDH, >2 nodal regions involved PRESENTATION - can be either side of diaphragm Lymphadenopathy: mediastinal > neck > axilla > lung OTHERWISE NOTEWORTHY hilum; painless and without inflammatory signs Usually extranodal B-symptoms: fever, weight loss, night sweats Grading is not so important ( > 10 %months) in 6 Pruritis Superior vena cava syndrome 30  Charlotte Eikaas 2023/24 HEMATOLOGIC CANCER- HODGKIN’S LYMPHOMA EPIDEMIOLOGY DIAGNOSIS Less common than NHL (40% VS 60%) Excisional biopsy- whole node Bimodal distribution- young adults and 60+ Staged by Ann-Arbor system (see previous page) F < M (slight) Caucasians are at highest risk Possible genetic predisposition; often in small families TREATMENT RISK FACTORS & ETIOLOGY Early stage: RT, chemo (2-4xABVD) or combination Advanced stage: chemo (6-8x ABVD); possibly RT for Pathogens: EBV, Mycobacterium, Helicobacter, HCV, residual disease HTLV-1/2, HHV8 Borellia Campylobacter , Relapses: high-dose chemo + autologous stem cell Immunosuppression transplant; further relapse → Brentuximab Vedotin or Diet, alcohol, smoking Anti-PDL-1 Herbicides Oncogenes · ionizing radiation PROGRESSION & PROGNOSIS SUBTYPES Spread: mediastinal → cervical → para-aortic nodes Classic subtypes: nodular sclerosis, mixed cellularity, Better prognosis than NHL lymphocyte predominant Non-classic type has best prognosis; lymphocyte- depleted classic HL has worst More common in younger children A B Bad prognostic factors: bulky mediastinum, extranodal Loss of B-cell markers (CD20, CD45) involvement, elevated ESR, >3 node regions involved C CD15 and CD30 + % Causes of death: secondary leukemia, cardiac/ pulmonary Reed-Sternberg cells- -5 1% of tumor mass complications May be EBV-related Non-classic subtype- nodular lymphocyte predominant HL ↳ OTHERWISE NOTEWORTHY good prognosis More common in young males Has B-cell markers (CD20, CD45) No leukemic phase Popcorn cells Other: lymphocyte-depleted HL, unclassified HL PRESENTATION - > above diaphragm always Three unique features 1. Localized to single axial group of nodes- cervical MC 2. Predictable spread 3. Rarely extranodal 31  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 - CNI Best prognosis: botryoid, spindle cell RMS cerebellum , Young children → pilocytic astrocytoma ( optic nerves) 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 mixed cellularity; treated with chemo + RT; lower RT dose than adults; 90% cured 34  Charlotte Eikaas 2023/24 GENETIC SYNDROMES ASSOCIATED WITH CHILDHOOD CANCER BONE SARCOMAS Familial retinoblastoma: Rb1 mutation; retinoblastoma + 5-7% of childhood malignancies osteosarcoma; 40% are hereditary Surgical biopsy for diagnosis Li-Fraumeni syndrome: TP53 mutation; adrenocortical carcinoma, Osteosarcoma: 70%; about 50% are located close to the knee; STS, osteosarcoma, CNS tumors several genetic links (←); treatment = chemo → surgery → chemo. 75% long-term survival HNPCC: MSH2/MLH1/PMS2 mutation; colon cancer + glioma Ewing sarcoma: 40% have symptoms of inflammation; FAP: APC mutaton; colon cancer, medulloblastoma, treatment = chemo → surgery → RT. Localized disease = 50% hepatoblastoma cured; disseminated → 20% 5YS Gorlin syndrome: PTCH mutation; basal cell carcinomas + medulloblastoma WILMS TUMOR Neurofibromatosis 1: NF1 mutation; astrocytoma, optic nerve AA 3-4 y/old; 95% before 7 y/old gliomas myelomonocytic leukemia, ALL, rhabdomyosarcoma, Treatment: chemo without biopsy → radical surgery malignant peripheral nerve sheath tumor (MPNST); also → post-op chemo + RT classically presents with neurofibromas, Lisch nodules and Cafe Staging: I = only kidney+ fully excised; II= beyond au Lait spots kidney but fully excised; III = residual tumor confined Neurofibromatosis 2: NF2 mutation; bilateral acoustic to abdomen; IV= bilateral renal involvement schwannomas, multiple meningiomas, spinal ependymomas Ataxia-telangiectasia: ATM mutation; lymphoma, leukemia Wiskott-Aldrich syndrome: WAS mutation; NHL NEUROBLASTOMA Bloom syndrome: BLM mutation; NHL, Wilms tumor, AA 1-2 y/old; 90% before 5 y/old deletion of. short arm of Gr osteosarcoma Cytogenetic disorders in 30%: N-MYC, others (15-1) Fanconi anemia: FANCA mutation; AML, hepatoma Location: retroperitoneal (60-80%) > mediastinum > pelvis 22-5 %) 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