Lung cancer. Lung cancer basics

Onclgy cre learning series by Harmesh R. Naik, MD. Lung cancer Lung cancer basics Incidence: A wrldwide epidemic : Mre than 1 millin new cases per year and mre than 900,000 deaths annually. Overall mrtality rate frm lung cancer has risen markedly ver the past century. In United states f America: 2010 statistics per American cancer sciety cancer facts and figures: 2010 2010 statistics per American cancer sciety cancer facts and figures: 2010 Estimated new cases Estimated deaths Ttal Males Females Ttal Males Females USA 222,520 116,750 105,770 157,300 86,220 71,080 Michigan 8,150 5,830 Abut 85% are nn small cell and abut 15% are small cell lung cancer The incidence is declining in men frm 1984 t 2006 data The incidence is reaching a plateau in wmen after years f increase Lung cancer accunts fr mre deaths than any ther cancer in bth men and wmen The mrtality rate frm lung cancer in American men declined frm 1990 t 2006 reflecting a decrease in smking prevalence amng men since the 1950s. Lung cancer mrtality has been stable after years f increase fr American wmen. Risk factrs: Tbacc: Mst imprtant risk factr. Risk increases with quantity f cigarettes and duratin f smking. Asbests (with tbacc) ccupatinal r envirnmental expsure t secndhand smke Radn, asbests Certain metals (chrmium, cadmium, arsenic) Inizing radiatin Air pllutin, A histry f tuberculsis Genetic susceptibility plays a cntributing rle in the develpment f lung cancer, especially in thse wh develp the disease at a yunger age. Preventin strategy: Avid tbacc expsure Chempreventin ptins are nt yet successful Summarized By Dr. Harmesh Naik Nvember 2010 update 1 P a g e

Onclgy cre learning series by Harmesh R. Naik, MD. Symptms / signs: Mst patients with lung cancer present with new signs r symptms. New r wrsening cugh is the mst cmmn symptm. Hemptysis Dyspnea. Chest pain (pleuritic) Weight lss, lss f appetite. Symptms f metastatic disease such as bne pain Cmmn presentatins Signs f pst bstructive pneumnitis: prductive cugh, r fever, mre cmmn in patients with centrally lcated tumrs. Pleuritic chest pain r nnprductive cugh mre cmmn in patients with peripheral lesins. Harseness f vice suggests vcal crd paralysis with entrapment f the recurrent laryngeal nerve. It is seen mre ften n the left than the right side because f the lnger curse f the left nerve arund the arta. Swelling f the face and mst ften the right arm may ccur wing t the superir vena cava syndrme. Pan cast syndrme : Seen with apical tumrs. Symptms are Shulder pain Lwer brachial plexpathy Hrner's syndrme Unilateral cnstricted pupil Facial dryness Ptsis caused by damaged sympathetic nerves. Patients with pleural r pericardial effusins may present with dyspnea, cugh, and chest pain. Paraneplastic syndrmes Adencarcinma and large-cell carcinma, ften are present in the peripheral lung and are indicated by pleural effusins r signs r symptms f metastatic disease. Sme patients present asymptmatically with an incidental lung lesin n radigraph r CT scan f the chest. General bservatins abut histlgic patterns: Squamus cell Central lcatin 95% Smkers 60% Metastases Hypercalcemia Cnversely, squamus cell carcinma, the nn small-cell lung cancer mst assciated with smking, is decreasing in incidence. In general, squamus cell carcinma tends t ccur centrally with endbrnchial lesins, and mre than half the time with n evidence f metastases n staging tests; hwever, subclinical metastases ften exist. Adencarcinma Peripheral lcatin 50% Smkers, 50% nn smkers 80% Metastases Hypercagulability Summarized By Dr. Harmesh Naik Nvember 2010 update 2 P a g e

Onclgy cre learning series by Harmesh R. Naik, MD. Hypertrphic pulmnary stearthrpathy Mre lder nnsmkers and wmen Half f patients with adencarcinma f the lung have never smked, and the rapid rise in incidence f this type f cancer in the past 20 years may reflect the aging f the ppulatin. The use f filtered cigarettes may result in smaller smke particles entering int smaller airways with a resulting increased incidence f adencarcinma in peripheral pulmnary sites. Brnchilalvelar cell carcinma Preventin Subtype f adencarcinma Nnsmkers Usually female Often bilateral, diffuse, multi-fcal Infiltrates r multiple ndules Diagnsis Multifcal recurrence Sensitive t epidermal grwth factr receptr inhibitin Staging Slw grwth Late metastases utside f lung Brnchilalvelar cell carcinma, which represents 20% f cases f adencarcinma A distinct clinic-pathlgic presentatin Treatment Large-cell Peripheral lcatin 90% Smkers 80% Metastases Small-cell Fllw up Central lcatin Almst 100% smkers Almst 100% metastases Eatn-Lambert syndrme SIADH Survivrship Ectpic ACTH Screening fr lung cancer: cntrversial Screening fr early lung cancer detectin has nt yet been prven t reduce mrtality. Detectin by chest x-ray, analysis f cells in sputum, and fiber-ptic examinatin f the brnchial passages has shwn limited effectiveness in reducing lung cancer deaths. Newer tests, such as lw-dse spiral cmputed tmgraphy (CT) scans and mlecular markers in sputum, have prduced prmising results in detecting lung cancers at earlier, mre perable stages in high-risk patients, but have nt yet been shwn t reduce lung cancer deaths. There are cnsiderable risks assciated with lung bipsy and surgery that must be cnsidered when evaluating the risks and benefits f screening. The Natinal Lung Screening Trial is a clinical trial t assess whether screening individuals at high risk fr lung cancer with spiral CT r standard chest x-ray can prevent lung cancer deaths. Launched in 2002, results frm the study are expected by 2010-2011. Summarized By Dr. Harmesh Naik Nvember 2010 update 3 P a g e

Onclgy cre learning series by Harmesh R. Naik, MD. Summary f screening: Screening tests, such as spiral CT scans, have nt yet been fund t reduce lung cancer mrtality. Lk fr updated infrmatin n Medline: Data is evlving. Diagnsis cnfirmatin: A bipsy is necessary. Methds f diagnsis: A brnchscpy: Centrally lcated pulmnary tumrs : CT guided bipsy: fr peripheral lesins. Vide thracscpy. Sputum cytlgy. A lymph nde bipsy, A mediastinscpy r an anterir mediastintmy. Pleural fluid cytlgy. Bipsy f metastatic site: Any histlgically cnfirmed findings f nn small-cell lung cancer metastasis by CT, PET, r bne scan wuld preclude resectin. Nn small-cell lung cancer Nn small-cell lung cancer : three distinct histlgical types Squamus cell carcinma (epidermid) Adencarcinma (including the slw-grwing, ften diffuse brnchilalvelar cell subtype) Large-cell carcinma These histlgical types f lung cancer are classified tgether as Nn small cell lung cancer n a clinical basis. They are all ptentially cured by lcalized disease resectin. They respnd nly mdestly t chemtherapy. Radiatin therapy can prvide lcal tumr cntrl in many patients with lcally unresectable disease. Cure is rare in unresectable disease. Nn small-cell lung cancer Staging studies / staging wrk up: Staging is imprtant in the selectin f therapy in patients with nn small-cell lung cancer. Clinical staging includes: A cmplete physical examinatin: Lk fr signs f spread CT scan f the chest and abdmen (frequent metastases are fund in the adrenal gland) A bne scan A CT scan r MRI f the head. PET scan: Lk fr updated infrmatin n Medline: Data is evlving. A psitrn emissin tmgraphy (PET) as a separate study r cmbined with CT scan (PET/CT fusin scan), when available; A psitive PET scan finding that crrelates with findings f the CT scan, such as mediastinal lymph nde invlvement beynd the primary lesin, suggests distant metastases and unresectability. Summarized By Dr. Harmesh Naik Nvember 2010 update 4 P a g e

Onclgy cre learning series by Harmesh R. Naik, MD. PET scans are used rutinely in the staging prcess t identify patients wh may qualify fr surgical resectin, althugh their impact n actual utcmes is unprven. PET scans may detect lesins unseen by ther radilgic tests, but tw trials have reprted cntradictry results n whether PET scans reduce needless thractmy Patients with false-psitive PET scan findings may be denied ptential cure by surgery; hwever, the high rate f subclinical metastases in all patients with early-stage disease lessens the impact f false-psitive results. Staging f Nn small-cell Lung Cancer See detailed AJCC system fr updated infrmatin Early-Stage Disease (Stage I r II) Brdered by lung r visceral pleura 2 cm r mre distal t the carina N invasin f mediastinal lymph ndes Can include lcally advanced invasin f chest wall (including superir sulcus), diaphragm, parietal pleura, r pericardium Reginally Advanced Disease (Stage III) Mediastinal invlvement Distant Metastases (Stage IV) Treatment f Nn-Small-Cell Lung Cancer Clinical trial participatin is apprpriate fr eligible patients. Stage I resectable disease Surgery is the treatment f chice fr patients with early-stage (stage I ) nn small-cell lung cancer. Five years after resectin, apprximately 50% t 70% f patients with stage I nn small-cell lung cancer (n hilar lymph nde invlvement) are recurrence free Use f adjuvant (pstperative) chemtherapy fr patients with early-stage disease and represent a new standard f care. Three large randmized studies have shwn that in patients with early-stage (stage IB and II) nn small-cell lung cancer, treatment after surgery with chemtherapy cnsisting f cmbinatin Paclitaxel and Carbplatin r Cisplatin with Etpside r Vinrelbine imprves abslute verall survival by 4% t 15% at 5 years Use f adjuvant raditherapy in patients with early-stage nn small-cell lung cancer has nt been fund t cnfer a survival benefit, and may be assciated with increased mrtality in this setting. Stage II resectable disease Surgery is the treatment f chice fr patients with early-stage (stage II) nn small-cell lung cancer. Five years after resectin, apprximately 20% t 40% f patients with stage II disease (hilar lymph nde invlvement) are recurrence free Use f adjuvant (pstperative) chemtherapy fr patients with early-stage disease and represent a new standard f care. Summarized By Dr. Harmesh Naik Nvember 2010 update 5 P a g e

Onclgy cre learning series by Harmesh R. Naik, MD. Three large randmized studies have shwn that in patients with early-stage (stage IB and II) nn small-cell lung cancer, treatment after surgery with chemtherapy cnsisting f cmbinatin Paclitaxel and Carbplatin r Cisplatin with Etpside r Vinrelbine imprves abslute verall survival by 4% t 15% at 5 years Use f adjuvant raditherapy in patients with early-stage nn small-cell lung cancer has nt been fund t cnfer a survival benefit, and may be assciated with increased mrtality in this setting. Patients with stage III disease (Usually with mediastinal lymphadenpathy) Multi-mdality therapy is strngly recmmended based n clinical data. 5-year survival rate f 2% t 15%, depending n the extent f mediastinal disease. Chem-RT is better than RT alne fr stage III: A meta-analysis f 11 randmized trials shwed that, Cisplatin-based cmbinatin chemtherapy plus radiatin therapy yielded a 10% relative reductin in the risk fr mrtality, cmpared with radiatin therapy alne. Cncurrent chemtherapy and radiatin therapy is better than sequential chemtherapy fllwed by radiatin. Ne-adjuvant chemtherapy is used befre surgery, in patients with ptentially resectable disease (that is, thse with minimal mediastinal lymph nde invlvement), An ptimal sequence f chemtherapy, radiatin therapy, and surgical resectin is under study. Superir sulcus tumrs are a special sub grup f stage III disease in which lcal invasin causes pain in the shulder r brachial plexus. Five-year survival rates f 20% have been reprted fr selected studies in which radiatin therapy, surgery, r bth were used. Patients with stage IV disease: with distant metastases. Median survival f untreated patients: 6- t 8-mnths. Must assess perfrmance status prir t treatment decisin. Palliative Chemtherapy is generally ffered nly t patients whse perfrmance status is gd ( patients wh are nt bedbund during the day). A Mdest verall survival benefits (10 t 20 weeks mre cmpared t the median survival f untreated patients) have been shwn nly in gd perfrmance status patients. Cisplatin based therapy is cnsidered standard f care. Several platinum cmbinatins are equivalent. The type f platinum-based cmbinatin chemtherapy used has nt had an effect n efficacy f treatment. Cmbinatins are better than single agent which is better than best supprtive care in randmized clinical trials. Secnd- r third-line chemtherapy has been used fr patients with recurrent disease. Prspective randmized trials have shwn a small survival advantage (median survival, 8 weeks) with the use f Dcetaxel r Pemetrexed; hwever, raditherapy in this setting is nt helpful and may increase mrtality. Patients with stage 4 nn small-cell lung cancer and pr perfrmance status, d nt usually derive any benefit frm chemtherapy and shuld be managed with supprtive r palliative care. Brnchilalvelar cell carcinma subgrup: Seems particularly sensitive t epidermal grwth factr receptr inhibitin; amng 90 patients with advanced disease, apprximately 20% had a majr respnse and 30% stable disease with ral Gefitinib. Tyrsine kinase inhibitrs represent a new therapeutic advance fr patients with nn small-cell lung cancer. Summarized By Dr. Harmesh Naik Nvember 2010 update 6 P a g e

Onclgy cre learning series by Harmesh R. Naik, MD. Fr patients with recurrence f metastatic disease, Erltinib has cnferred a small verall survival advantage (median survival, 8 weeks). Up t 50% f patients with brnchilalvelar cell carcinma have sustained respnse r stability with Gefitinib. A subgrup f patients has specific mutatins in the epidermal grwth factr receptr gene, which causes increased grwth-factr signaling, cnferring a rapid and dramatic clinical respnse t the tyrsine kinase inhibitr Gefitinib. Brnchial bstructin: Radiatin therapy may be palliative fr patients with symptmatic lcal invlvement, such as tracheal r brnchial cmpressin, bny metastases, hemptysis, r superir vena cava syndrme. In sme instances, endbrnchial laser therapy, crytherapy, r implantatin f radiactive seeds may shrink bstructing lesins in the prximal brnchus. Expandable metal stents inserted brnchscpically int the trachebrnchial tree can imprve pulmnary functin in patients with extrinsic brnchial tumr cmpressin. Special situatins: Mnthly intravenus bisphsphnate therapy with Pamidrnate r Zledrnate decreases skeletal-related events fr patients with bny metastases. A slitary brain metastasis with n evidence f extra cranial tumr Patients wh have relapses after resectin f primary nn small-cell lung cancer as manifested by a slitary brain metastasis with n evidence f extra cranial tumr may have prlnged disease-free survival after surgical excisin and pstperative whle-brain radiatin therapy cmpared with thse wh receive radiatin therapy alne. Subsequent tumr recurrence in the brain can be palliated with further surgery r with steretactic radi surgery. Pleural effusin: Thraccentesis and pleurdesis Patients with malignant pleural effusins d nt benefit frm raditherapy Palliative chemtherapy fr palliatin alne may be ffered. A secnd primary tumr. Patients wh have relapses in the frm f a slitary pulmnary ndule usually have a secnd primary tumr. Subsequent resectin f this new lesin plus adjuvant chemtherapy may result in lng-term survival in selected patients. Survival: American cancer sciety data (2010 update) The 5-year survival rate fr all stages cmbined is nly 16%. The 5-year survival rate is 53% fr cases detected when the disease is still lcalized, but nly 15% f lung cancers are diagnsed at this early stage. The 5-year survival fr small cell lung cancer (6%) is lwer than that fr nn-small cell (17%). The 1-year relative survival fr lung cancer increased frm 35% in 1975-1979 t 42% in 2002-2005, largely due t imprvements in surgical techniques and cmbined therapies. Treatment f Nn-Small-Cell Lung Cancer: Summary: Stage I Summarized By Dr. Harmesh Naik Nvember 2010 update 7 P a g e

Onclgy cre learning series by Harmesh R. Naik, MD. Surgery and adjuvant chemtherapy fr selected Curative intent Stage I: 50% t 70% lng-term disease-free survival Stage II Surgery and adjuvant chemtherapy Curative intent Stage II: 20% t 40% lng-term disease-free survival Stage III Mediastinal invlvement Chemtherapy and raditherapy in stage III: 5% t 20% lng-term disease-free survival In selected patients, chemtherapy fllwed by surgery Stage IV Distant metastases Chemtherapy fr gd perfrmance status patients Palliative intent Small-cell lung cancer Small-cell lung cancer Small-cell lung cancer accunts fr apprximately 15% f all cases f lung cancer Almst always assciated with tbacc use. Small cell lung cancer is cnsidered a systemic disease: Almst all patients have disseminated disease n initial presentatin, with mst having evidence f metastatic disease n CT scan. Even patients wh present with lcalized disease almst always have cncurrent micr metastases. Small-cell lung cancer has a much mre aggressive clinical curse than the ther histlgical types. Small-cell lung cancer is much mre respnsive t chemtherapy and raditherapy than the ther histlgical types, but the cure rate remains lw. Staging fr SCLC: Limited stage: Lcalized disease that can be encmpassed within a radiatin therapy prt, usually with cnfinement t ne hemthrax lymph nde, the mediastinum, and supraclavicular lymph ndes. Abut 30% f patients with small-cell lung cancer have limited-stage disease. Mst 2-year disease-free survivrs have limited-stage disease at presentatin. Median survival: 16 t 24 mnths. Extensive stage: Tumr beynd the cnfines f a radiatin prt. Median survival is nly 8 t12 mnths. Lng-term disease-free survival is rare. Staging studies fr SCLC: Mst staging studies are nninvasive (staging des nt change need fr chemtherapy). Summarized By Dr. Harmesh Naik Nvember 2010 update 8 P a g e

Onclgy cre learning series by Harmesh R. Naik, MD. A CT scan f the chest and abdmen up t adrenals. A CT r MRI f the head (3% t 7% f patients have asymptmatic brain metastases at presentatin). A radinuclide bne scan. Bne marrw bipsies are nt required in these patients. PET scans can identify the presence f limited-stage disease and help define radiatin prts. Special Cnsideratins prir t treatment: Incidentally detected small lesins: Patients wh can underg cmplete resectin befre chemtherapy have an even better prgnsis than thse wh cannt, but this scenari is rare. Sme f these patients may actually have atypical carcinid r well-differentiated neurendcrine tumrs, which are much less likely t metastasize but can nevertheless be histlgically mistaken fr small-cell lung cancer. Thse with central nervus system r liver metastases have the wrst prgnsis. Treatment fr SCLC: Gd prgnstic factrs: Limited-stage disease Female sex Gd perfrmance status. Main treatment fr patients with small-cell lung cancer is palliative systemic therapy. Clinical trial participatin is apprpriate fr eligible patients. Fr patients with limited-stage small-cell lung cancer: Chemtherapy + chest radiatin is standard f care. Tw meta-analyses : Chem-RT is better than chemtherapy alne. A 5% abslute imprvement in 3-year survival rates favring chemtherapy and radiatin therapy cmpared with chemtherapy alne. The current standard treatment : Cisplatin and Etpside with chest radiatin therapy during the first tw t three cycles f chemtherapy. A median survival f 18 t 24 mnths A 2-year survival likelihd f 40% t 50%. Mdern regimens: less than 3% treatment-related mrtality. Superir vena cava syndrme at initial presentatin: Chemtherapy, with r withut radiatin therapy, is apprpriate Prphylactic cranial irradiatin (PCI) shuld be cnsidered fr patients wh have a cmplete remissin after chem-chest RT. A meta-analysis f seven randmized trials evaluating PCI in patients with a cmplete respnse: Shwed decreased brain invlvement Imprved disease-free and verall survival (15% t 21% increased survival cmpared with untreated patients) at 3 years. Patients wh underg PCI fr SCLC and wh survive fr mre than 2 years frm start f therapy experience a decline in neurpsychlgical functin. The degree f this impairment is cntrversial. Fr patients with extensive-stage small-cell lung cancer: Summarized By Dr. Harmesh Naik Nvember 2010 update 9 P a g e

Onclgy cre learning series by Harmesh R. Naik, MD. Patients with extensive-stage disease and pr perfrmance status (that is, thse wh are usually bedbund) may derive significant shrt-term palliative benefit and imprved survival frm chemtherapy. Cmbinatin palliative chemtherapy Cmbinatin palliative chemtherapy alne may result in a 70% t 85% respnse rate and a 20% t 30% cmplete respnse rate. Median survival is 8 t 12 mnths, with survival beynd 2 years rare. Mst f these chemtherapeutic regimens are platinum-based, cnsisting f Cisplatin and Etpside r Carbplatin and Etpside. Mnthly intravenus bisphsphnate administratin with Pamidrnate r Zledrnate decreases skeletal-related events fr patients with bny metastases. Prphylactic cranial irradiatin can be cnsidered fr cmplete respnders with extensive-stage disease t reduce the 60% actuarial risk fr develping brain metastases within 2 years. Fr patients with extensive-stage disease and very pr perfrmance status ften caused by advanced age and c mrbid cnditins, single-agent intravenus r ral agents can prvide palliatin. Clinical trials are underway t identify new systemic ptins, particularly targeted therapies, fr patients with extensive-stage disease. In the past 30 years, n incremental prlngatin f survival has been nted in thse with extensive-stage disease since the first use f cmbinatin chemtherapy. Recurrent SCLC: Survival is shrt after small-cell lung cancer recurrence. Patients wh are primarily resistant t therapy r have received many chemtherapeutic regimens rarely respnd t mre therapy. Thse wh respnd t initial chemtherapy and have a relapse lnger than 6 mnths after the end f treatment are mre likely t respnd t additinal chemtherapy than nn-respnders. N ne drug r regimen is cnsidered standard in this setting. Risk f secnd primary lung tumrs: Lng-term survivrs f small-cell lung cancer with n recurrence beynd 5 years usually have limited-stage disease at presentatin. Beynd 5 years, mst subsequent mrtality is attributable t secnd primary lung tumrs, ften f distinct histlgical type. Retrspective analyses suggest that cntinued smking might increase the risk fr a secnd primary lung tumr after successful treatment f small-cell lung cancer. Cunsel all patients abut smking cessatin. Summary fr SCLC: Chemtherapy imprves median survival in patients with small-cell lung cancer (SCLC) substantially cmpared with surgery r raditherapy alne. Patients with extensive-stage SCLC and pr perfrmance status may derive significant shrtterm palliative benefit and imprved survival frm chemtherapy. Chemtherapy plus radiatin results in a 5% abslute imprvement in 3-year survival in patients with limited-stage SCLC cmpared with chemtherapy alne. Summarized By Dr. Harmesh Naik Nvember 2010 update 10 P a g e

Onclgy cre learning series by Harmesh R. Naik, MD. Prphylactic cranial irradiatin is an ptin fr cmplete respnders with extensive-stage SCLC t reduce the risk fr brain metastases. Cntinued smking may increase the risk fr a secnd primary lung tumr after successful treatment f small-cell lung cancer. Overall, 10% f patients with small-cell lung cancer are disease free 2 years after cmpletin f chemtherapy. By 10 years, half f these lng-term survivrs die f small-cell cancer recurrence r a new nn small-cell lung cancer. Slitary Pulmnary Ndule Slitary Pulmnary Ndule Althugh mst patients with pulmnary ndules require either a diagnstic bipsy r a plan fr bservatin, sme highly selected may require n further fllw-up. Cmparisn f Benign and Malignant Features f a Slitary Pulmnary Ndule Benign Features Yunger age N tbacc use <1 cm size Regular brder Increased density n CT scan Lw r absent uptake n PET scan Dubling time >1 year Benign pattern f calcificatin Malignant Features Older age Tbacc use >1 cm size Irregular brder Lwer density n CT scan Increased uptake n PET scan Dubling time <1 year Malignant patterns f calcificatin A bipsy shuld be perfrmed in patients with pulmnary ndule/s suspicius fr malignancy based n clinical signs r cntext (with a higher pretest prbability fr malignancy). What is the best diagnstic apprach fr the evaluatin f and precise labeling criteria fr suspicius slitary pulmnary ndule: Cntrversial A direct surgical resectin Needle bipsy: A needle bipsy can yield false-negative results. Percutaneus needle bipsy fllwed by ther staging studies allws fr assessment f resectability. Summarized By Dr. Harmesh Naik Nvember 2010 update 11 P a g e

Onclgy cre learning series by Harmesh R. Naik, MD. Pulmnary ndules mst likely t be benign based n clinical signs r cntext (with a lwer pretest prbability fr malignancy) shuld be mnitred by fllw-up serial CT scans f the chest t assess interval grwth. A sample mnitring schedule is 3 t 4 mnths fr the first CT scan, 6 t 8 mnths fr the secnd CT scan, and a third scan at 1 year. Summarized By Dr. Harmesh Naik Nvember 2010 update 12 P a g e