—cough, sputum (salty suggests bronchoalveolar), hemoptysis, dyspnea, chest pain, wheezing, dysphagia, brachial plexus (Pancoast tumour), hoarseness, Horner’s syndrome, superior vena cava syndrome

—bone pain, jaundice, seizures, headaches, adrenal lesions, skin lesions

—weight loss, anorexia, fatigue

—based on mediastinoscopy. Nodes are designated 1–14. N3 node (supraclavicular) = position 1, N2 nodes = position 2–9, and N1 nodes = position 10–14

—limited stage 20–40% 2-year survival, 16–24 months median survival, extensive stage <5% 2-year survival, 6–12 months median survival. Median survival post-relapse 4 months

—for smokers of <20 pack year, the risk of developing lung cancer decreases significantly after 15 years of abstinence, but still slightly higher than non-smokers

(stage IIIB or greater)—distant metastasis, mediastinal LN metastasis, trachea/contralateral main bronchi involvement, SVC obstruction, malignant pleural effusion, recurrent laryngeal nerve paralysis, SCLC (unless very early)

—significant pre-existing lung disease, cardiomyopathy, connective tissue disease (SLE, scleroderma), prior radiation to same body region, pregnancy

—squamous cell carcinoma, hemoptysis, uncontrolled cerebral metastases, non-healing wounds, uncontrolled hypertension/proteinuria, bleeding diatheses, recent trauma/surgery

—clinical factors include women, Asian, never smokers, and adenocarcinoma. With all 4 factors, response rate 50% (compared to 10% normally). Pathologic predictive factors include EGFR mutation and high EGFR gene copy number

—accounts for approximately 80% of mesothelioma. Risk of mesothelioma is higher with amphiboles/blue asbestos than chrysotile/white asbestos. Asbestos fibers may irritate the pleura, sever or pierce the mitotic spindle of cells and disrupt mitosis, induce generation of iron-related reactive oxygen species, and phosphorylate MAP kinases and ERK 1 and 2. Tumor usually starts from parietal pleura and invades locally

—pleural (pleural effusion, pleuritic chest pain, dyspnea, SVC obstruction), peritoneal (ascites, abdominal pain, bowel obstruction), pericardial (pericardial effusion, tamponade)

—miliary spread, liver, lung, bone, and/or adrenal lesions

—weight loss, anorexia, fatigue

—male, poor performance status, sarcomatoid subtype, leukocytosis, anemia, thrombocytosis, advanced stage, high PET ratios

—stage I = 16 months median survival, ≥3 adverse prognostic factors = <6 months median survival, stage II–IV = 10 months median survival

(resectable disease)—surgery (pleurectomy/decortication, extrapleural pneumonectomy, debulking) is controversial and of questionable benefit. Pleurectomy/decortication should be the first option for patients with operable early stage disease and is an option for patients with locally advanced disease who are not candidates for extrapleural pneumonectomy. Extrapleural pneumonectomy should be considered for highly selected patients (age <55, performance status ≤1, stage I or II, epithelioid histology) and only after a good response to neoadjuvant chemotherapy, to be followed by adjuvant radiation. Otherwise, treat as unresectable disease

(unresectable disease)—palliative chemotherapy (cisplatin–pemetrexed with vitamin B12 and folic acid supplementation or cisplatin–gemcitabine). Second-line options include repeating cisplatin–gemcitabine, cisplatin–pemetrexed, and vinorelbine. Pleurodesis or indwelling pleural catheters should be considered if recurrent effusion

—dyspnea, cough, chest pain, hoarseness, dysphagia, superior vena cava obstruction

—weight loss, anorexia, fatigue

—myasthenia gravis (30–50%, diplopia, ptosis, dysphagia, weakness, fatigue), pure red cell aplasia (5–15%), pure white cell aplasia, pancytopenia, hypogammaglobulinemia (recurrent infections, diarrhea), rheumatologic diseases, and endocrinopathies. Note that remission of thymoma does not necessarily correlate with improvement of paraneoplastic syndromes

(resectable disease)—resection (usually including adjacent lung parenchyma and pericardium) ± adjuvant radiation ± (neo)adjuvant chemotherapy [cisplatin–doxorubicin–cyclophosphamide (preferred for thymoma), carboplatin-paclitaxel (preferred for thymic carcinoma), cisplatin–etoposide]

(unresectable disease)—palliative radiation ± palliative chemotherapy [cisplatin–doxorubicin–cyclophosphamide (preferred for thymoma), carboplatin-paclitaxel (preferred for thymic carcinoma), cisplatin–etoposide]

—locally advanced or metastatic unresectable disease, residual disease post-resection, and complete resection of invasive thymoma or thymic carcinoma

—BRCA1 is associated with basal-like subtype and triple negative (ER negative, PR negative, Her2 negative) phenotype. BRCA2 is associated with luminal subtype. Phase II data have shown that these tumors are particularly sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase (PARP) inhibitors due to defects in DNA homologous recombination repair from BRCA mutation

—spiculated, crab-like, puckering lesions, architectural distortion, clustered microcalcifications

—if average risk population, mammogram q2 years starting age 50 (may begin annual mammogram screening earlier at age 40); if high risk, annual clinical breast examination and mammography (starting 5-10 years younger than age of onset for youngest proband if strong family history)

—young age, advanced stage (especially nodal status and tumor size), high grade, Her2/neu+, ER–, PR–, lymphatic/vascular invasion

—biopsy to try to distinguish recurrence from new primary, metastatic workup. If isolated local recurrence, resection/completion mastectomy ± radiation. Hormonal and/or chemotherapy may also be considered

—modified radical mastectomy, radical mastectomy. Indications for mastectomy include multicentric disease, diffuse malignant appearing microcalcifications on mammography, prior breast radiation, and pregnancy. Relative indications include large tumor (>5 cm), connective tissue disease (radiation contraindicated), and patient preference. Poorer cosmesis compared to breast-conserving surgery

—excisional biopsy, lumpectomy, partial mastectomy, quadrantectomy, wide local excision

—positive margin is defined as tumor touching ink and would require re-excision

—used in all invasive carcinoma. May be avoided if sentinel lymph node negative

—indicated for clinically node negative tumors. Contraindications include locally advanced breast cancer, any palpable lymph nodes, multifocal cancers, previous disruptive breast procedures, and adverse reactions to dyes. Proceed to ALND if positive nodes or unable to identify sentinel node

—degree of response to tamoxifen varies (ER + PR+ > ER + PR– > ER–PR+ > ER–PR–). Hormonal therapy is not given to patients with ER- and PR- cancers. Her2+ may also interfere with ER pathways

—for premenopausal women, consider tamoxifen × 5-10 years. For postmenopausal women, consider one of the following: anastrozole × 5 years, letrozole × 5 years, tamoxifen × 2–3 years followed by exemestane or anastrozole to complete 5 years of adjuvant hormonal therapy, tamoxifen × 5 years followed by letrozole × 5 years, or tamoxifen × 10 years. Consider aromatase inhibitors as first hormonal agent if >10% risk of relapse in first 2 years (e.g. ≥4 positive nodes, low ER or grade 3 disease)

—patients with slowly progressive disease, no visceral involvement, and minimal symptoms may be best served with a trial of endocrine therapy. For premenopausal women, consider tamoxifen or ovarian ablation + tamoxifen → aromatase inhibitor 1 → aromatase inhibitor 2 → fulvestrant → megestrol. For postmenopausal women, aromatase inhibitor 1 → tamoxifen → aromatase inhibitor 2 → fulvestrant → megestrol. Time to progression is 8 months with tamoxifen and 10 months with aromatase inhibitors

—the 21-gene recurrence score is a validated prognostic assay. It is applicable only to pathologically node-negative, hormone receptor-positive, and Her2-negative tumors to help with the decision of adjuvant chemotherapy. A score of <18, 18-30, and >31 defines the low (no chemotherapy recommended), intermediate (chemotherapy should be considered) and high risk (chemotherapy recommended) groups, respectively

(www.​adjuvantonline.​com)—this web-based program determines both recurrence risk and probability of survival with the use of adjuvant chemotherapy. However, it does not account for Her2 status

—younger age, high grade, ER negative, Her2 positive (possibly for anthracycline and taxane-based regimens)

—chemotherapy usually starts 4–10 weeks after surgery. Consider anthracycline followed by taxane (e.g. AC × 4 and weekly T × 12) for intermediate/high risk or node-positive breast cancer; anthracycline ± taxane + trastuzumab for Her2 positive breast cancer; CMF or DC if anthracycline contraindicated or preexisting heart disease

—single agent choices include anthracyclines (doxorubicin, pegylated liposomal doxorubicin), taxanes (paclitaxel, docetaxel, albumin-bound paclitaxel), anti-metabolites (gemcitabine, capecitabine), microtubule inhibitors (vinorelbine, eribulin, ixabepilone), and platinums (carboplatin, cisplaitin). Doublet regimens include doxorubicin-cyclophosphamide, carboplatin-gemcitabine, doxorubicin-paclitaxel, capecitabine-docetaxel, docetaxel-gemcitabine, and paclitaxel-gemcitabine

—patients with rapidly growing disease, especially involvement of visceral organs such as lung or liver may benefit more from chemotherapy compared to hormonal therapy due to a more rapid response. The choice of first line palliative chemotherapy depends on prior adjuvant chemotherapy, disease-free interval, patient’s performance status, and willingness/ability to tolerate side effects. Doublet regimens are associated with higher response rate, while single agents are better tolerated and are particularly appropriate for patients who are elderly or have poor performance status. Consider doublet regimens in patients that need a rapid response to relieve tumor-related symptoms. At eventual disease progression, change chemotherapy to non-cross-resistance single agents

—15–20% positive. Her2 positivity is a poor prognostic factor, but predicts response to trastuzumab, pertuzumab, ado-trastuzumab emtansine (T-DM1), and lapatinib

—Her2 positive disease should be treated with chemotherapy plus trastuzumab in the adjuvant/neoadjuvant settings. Do not give concomitantly with anthracyclines. In the metastatic setting, give chemotherapy and then maintenance trastuzumab until progression

—infusion reactions (40%, usually with first administration), cardiotoxicity, and pulmonary (rare)

—steroids, resection plus radiation, or radiation alone if resection not possible. Principles are similar for CNS recurrence

—dysphagia (74%), odynophagia (17%), upper GI bleed, epigastric pain

—dyspnea, cough, hoarseness, pain (retrosternal, back, RUQ)

—Virchow’s node, hepatomegaly, pleural effusion

—anorexia, fatigue, weight loss

(for Barrett’s)—consider screening gastroscopy in patients with risk factors (age ≥50, male, white race, chronic GERD >5 years, hiatal hernia, high BMI or intra-abdominal fat distribution, ±tobacco use, ±nocturnal reflux)

(for Barrett’s)—endoscopic surveillance with four-quadrant biopsies q3-5 years (if no dysplasia on biopsy), q6-12 months (low-grade dysplasia), q3 months (high-grade dysplasia without eradication therapy)

—weight loss >10%, dysphagia, large tumors, advanced age, lymphatic micrometastases

—dietician consult. Consider supplemental feeding if significant weight loss, but only if benefits greater than risk

(T3–4, N1, 65%, median survival 12–14 months)

(M1, 15%, median survival 9–12 months)

—no agreed upon surveillance program. Clinical assessment every 3 months during the first year, then every 6 months for a total of 5 years. Endoscopy as clinically indicated

(15%)—diffuse disease involving the entire stomach. Very poor prognosis; slightly better with superficial/expansive type (5–10%)

—35% proximal, 25% body, 40% distal

—epigastric pain, nausea and vomiting, dysphagia, upper GI bleed (melena, hematemesis), anemia, abdominal mass

—hepatomegaly, Virchow’s node (left supraclavicular LN), Irish’s node (left axillary LN), dyspnea, sister Mary Joseph nodule (umbilicus), Krukenberg tumor (ovaries)

—anorexia, fatigue, weight loss

—acanthosis nigricans, seborrheic keratosis (Leser–Trelat sign), inflammatory myositis, circinate erythema, cerebellar ataxia, thromboembolism, Cushing’s, carcinoid

—screening program in Japan may have contributed to the improved survival in that population through early detection of resectable gastric cancer. Not recommended outside countries with a high gastric cancer burden

—advanced stage, high grade, proximal location

—gastrectomy (total or subtotal) with D2 dissection

—same treatment approach as stage III if resectable disease. Otherwise, same treatment approach as metastatic disease

—may develop after a few years in patients who received subtotal or total gastrectomy

—no agreed upon surveillance program. q3month for first year, then every 6 months for a total of 5 years. Endoscopy as clinically indicated

—50% rectosigmoid, 18% descending colon, 11% transverse colon, 20% in the ascending colon and cecum

—the Vogelstein model of carcinogenesis developed based on analysis of FAP lesions. Normal epithelium → loss of 5q (e.g. APC, β-catenin) over decades → adenoma development → loss of 18q (e.g. k-ras) over 2–5 years → late adenoma → loss of 17p (e.g. p53) over 2–5 years → early cancer → loss of 8p → late cancer

(MSI)—may either be inherited as in HNPCC or spontaneous (15% of sporadic colon cancers). MSI is characterized by a decreased response to 5-fluorouracil-based adjuvant chemotherapy but improved prognosis

—about 40% of colon cancer has mutation in KRAS, which plays a key role in signal transduction downstream of EGFR. Tumors with wildtype K-ras have been shown to be more responsive to EGFR-based therapy (panitumumab, cetuximab) compared to mutant. This makes biologic sense as a mutated KRAS could continue to activate cell proliferation despite inhibition of EGFR

—bowel habit Δ, hematochezia, paradoxical diarrhea, tenesmus, abdominal pain, iron deficiency anemia

—RUQ pain, dyspnea

—weight loss, anorexia, fatigue

—Streptococcus bovis bacteremia and Clostridium septicum sepsis; colorectal cancer in 16–32% of patients with S. bovis bacteremia

—surgical resection + adjuvant chemotherapy (FOLFOX is the first choice. Other possibilities include capecitabine, 5–fluorouracil-leucovorin, infusional 5-fluorouracil if patient is not fit or has contraindications to oxaliplatin)

—if metastasis limited to liver and potentially resectable, consider liver resection plus perioperative chemotherapy. Radiofrequency ablation could be considered if patient unfit for surgery. If non-resectable disease, palliative chemotherapy (FOLFIRI ± bevacizumab, FOLFOX ± bevacizumab, or regorafenib. capecitabine or 5-fluorouracil/LV if patient unfit. Raltitrexed if 5-fluorouracil intolerant. Cetuximab–irinotecan or single-agent panitumumab in third line if KRAS wild type)

(stage I)—transanal excision only if T1, <30% circumference, <3 cm [<1.2 in.], margins >0.3 cm [>0.12 in.], mobile, within 8 cm [3.1 in.] of anal verge, no lymphovascular or perineural invasion, well or moderately differentiated tumor, and no evidence of lymphadenopathy on pretreatment imaging. Otherwise, total mesorectal excision via low anterior resection or abdominoperineal resection

(stage II and some stage III with no high risk feature (not fixed, not low <5 cm [2 in.], not bulky)—neoadjuvant radiation (short course, 1 week) + total mesorectal excision + adjuvant chemotherapy based on pathologic stage: FOLFOX × 12 if pathologic node positive (i.e. node positive); capecitabine × 8 if pathologic node negative. The type and the number of cycles of adjuvant chemotherapy are, however, not well established. Local guideline may vary. Neoadjuvant chemoradiation is also an appropriate option for these patients

(locally advanced disease, particularly if tethered to rectum or low-lying tumor <5 cm [<2 in.] from anus)—neoadjuvant chemoradiation (long course, 5 weeks, 5040 cGy plus infusional 5-fluorouracil or capecitabine) + total mesorectal excision + adjuvant chemotherapy for 4 months. Capecitabine or FOLFOX may be considered depending on the extent of downstaging with neoadjuvant chemoradiation and the pathologic stage

(stage IV)—see management for stage IV colon cancer

NOTE: FOLFOX = 5-fluorouracil, leucovorin, and oxaliplatin; FOLFIRI = 5-fluorouracil, leucovorin, and irinotecan; 5-fluorouracil/LV = 5-fluorouracil and leucovorin

—for patients with stage II and III disease who would be candidate for salvage treatment if recurrence, surveillance includes medical visit with history, physical examination and CEA every 3–6 months × 2 years, then every 6 months for the next 3 years. CT chest/abd (+ CT pelvis for rectal cancer) yearly × 5 years. Colonoscopy at 1 year and 3 years after initial diagnostic colonoscopy, then every 5 years. Proctosigmoidoscopy every 6 months for 5 years if rectal cancer but radiation not given

—leucovorin (LV) promotes formation of a stable ternary complex with thymidylate synthetase, permitting prolonged inhibition of the enzyme by 5-fluorouracil