1 I, Josh Foley, to the best of my knowledge, have no affiliation, sponsorships, honoraria, monetary support or conflict of interest from any commercial source. (God What a boring life I lead.) Times are bad. Children no longer obey their parents, and everyone is writing a book. Marcus Tullius Cicero ( BC) However I can be bribed with beer. Pearce s Rule Josh Foley It s dog eat dog out there and vice versa!!!!!!! Double what your patient tells you he smokes; Quadruple what he says he drinks! A Brief synopsis of Oncology Volume 2 Some of what you need to know to navigate oncology (and oncologists!!) Josh Foley MUN Family Practice: 1985 Wabush: Labrador : Fam. Dr. Burin, Nfld : Fam. Dr. Medicine Hat Ab.: 2004 present M.E. Yuell Cancer Clinic Director: palliative Care South east Alberta Zone AAHPM Diplomate in Palliative Medicine
2 Dr. Leonard H McCoy From Rural Doc to the Cancer Clinic I m not a magician, I m just an old country doctor. Star Trek: The deadly Years. Episode 4. Dec.8,1967. Oncology is NOT as complicated as it often seems. Hopefully I ll de mystify some things. (If I do this right I want some docs here today to say it can t be that simple.) Oncology is probably the most mystified field in medicine. (even worse than psychiatry!!!!!!!) Today s presentation Oncology (Greek) #1:What is cancer? (repeat from last year repeat attendees will be quizzed!!!!) Multiple Myeloma.(hardest to grasp in today s presentations) #2: Ovarian Ca Prostate Cancer.(a biggie!!!!!!!) Brace yourself for some arguing!!! Onco:.bulk, mass, tumor Logy:...study #3: Pancreatic and Stomach Ca Some tricks to make life easier #4: Some repeated stuff from last year. Mesothelioma > The repeats do not reflect laziness on my part.i really believe a few basic skills and a basic knowledge of what can go wrong and how we can manage problems make oncology much less scary. Cancer is a disease characterized by uncontrolled replication of cells. These mutations occur in the cellular genetic material of proto oncogenes and tumor suppressor genes. This starts with minor mutations in the genes of a cell or cells that gradually progresses through more and more aggressively mutant phases until a frankly malignant cell is produced. An example would be mild dysplasia seen on a PAP smear, progressing over time to moderate, then severe dysplasia, then carcinoma in situ, then invasive Ca. A proto oncogene is a normal gene that can become an oncogene due to mutations or increased expression. The resultant protein may be termed an oncoprotein and stimulates uncontrolled cell division. (accelerator) Tumor supressor genes are genes that protect against indiscriminate cell division (brake failure)
3 Therefore, cancer can be seen as a result of mutation to proto oncogenes and/or inactivation/mutation of tumor suppressor genes. These are key cogs in controlling cell division, and mutation allows uncontrolled cell division. They can also affect angiogenesis, thus allowing a tumor to grow it s own blood supply. They also can affect apoptosis. (programmed cell death) Genetic changes may also occur that protect metastatic cells on their journey to a new host site. Cancer development, then, is a slow but insidious march through serial gene mutations until we arrive at the frankly malignant cell. Leukemias may have as few as 12 critical mutations, some breast cancers have been found that have over 100. Multiple Myeloma myelo + oma..( "marrow" + "tumor"), also known as plasma cell myeloma a cancer of plasma cells; a white blood cell normally responsible for producing antibodies. In multiple myeloma, abnormal plasma cells accumulate in the bone marrow, where they interfere with the production of normal blood cells. Multiple Myeloma How is multiple myeloma diagnosed? It is part of a spectrum of diseases ranging from: monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. First described in 1848, MM is characterized by a proliferation of malignant plasma cells and a subsequent overabundance of monoclonal paraprotein (M protein) and immunoglobulins.. In many patients, multiple myeloma is first suspected when a routine CBC shows unusual counts or creatinine is elevated. Investigations may include a bone marrow biopsy or levels and types of monoclonal proteins produced. (SPEP) X rays to identify lytic lesions are commonly done. (Bone scans MAY be ( )ve ( Some people say up to 90%)..., so do skeletal surveys looking for punched out lesions.
4 Serum protein electrophoresis (SPEP) measures serum immunoglobulins and can identify a monoclonal immunoglobulin. Then, immunofixation or immunoelectrophoresis, is used to determine the exact type of abnormal antibody (usually IgG or M). Often described as a monoclonal peak Immunoglobulins are made up of protein chains: 2 long (heavy) chains and 2 shorter (light) chains. Portions of the protein chains may be excreted in the urine. This urine protein, known as Bence Jones protein, is the part of the light chain Soooo, where to start?? CBC, Labs Incl. creatinine SPEP Skeletal Survey Bence Jones urinary proteins OK..hard part over!!!!!!!!!!??bone marrow?? Symptoms of MM Anemia Bleeding Nerve damage Skin lesions Enlarged tongue (macroglossia).(i ve never seen this.) Bone tenderness or pain Weakness or tiredness Infections Pathologic bone fractures Spinal cord compression Kidney failure Stage I: Many patients with stage I myeloma show no symptoms. (If the cancer has affected kidney function, the prognosis may be worse regardless of the stage.) Factors characteristic of stage I include: Anemia Normal calcium level Low levels of M (monoclonal paraprotein) protein in the blood or urine Minimal bone damage on x ray
5 Stage II Stage lll More M protein is present in the body in stage II. Again, if kidney function is affected, then the prognosis worsens regardless of the stage. Anemia with a hemoglobin less than 85 Hypercalcemia. (Remember to correct for albumin) Advanced bone damage (more than three bone lesions) High levels of M protein in the blood or urine Prognosis The numbers listed WERE the approximate overall median survival using the International Staging System. (These survival times are measured from the point that treatment first started.) Many patients however, such as those with indolent or smoldering myeloma, have a good deal of time after diagnosis before treatment is started. These patients were treated anywhere from 5 to 25 years ago. Treatment since then has improved considerably and modern results are likely to be better. Stage I: Stage II: Stage III: 62 months 44 months 29 months Last Medical Review: 05/22/2014 Treatment for multiple myeloma may include :Chemotherapy Bisphosphonates Radiation Surgery Biologic therapy Stem cell transplant Plasmapheresis Traditional Chemo Chemo drugs that may be used to treat multiple myeloma include (among others): Melphalan Vincristine (Oncovin ) Cyclophosphamide (Cytoxan ) Etoposide (VP 16) Doxorubicin (Adriamycin ) Liposomal doxorubicin Bendamustine Rituximab
6 Corticosteroids Immunomodulating agents dexamethasone and prednisone. They can be used alone or combined with other drugs. Corticosteroids are also used to help decrease the nausea and vomiting that chemo may cause. The way immunomodulating agents affect the immune system isn t entirely clear. Thalidomide Lenolidamide (Revlamid) Pomalidomide (Pomalyst ) S/E include neuropathy, blood dyscrasias and clots, among others. Severely teratogenic!!!!!!!! (It s fun when I have to ensure my 65y/o lady with MM is not pregnant I love regulators..one of my daily chuckle!!) Proteasome inhibitors Bisphosphonates for multiple myeloma Work by stopping enzyme complexes (proteasomes) in cells that break down proteins important for keeping cell division under control. They appear to affect tumor cells more than normal cells. (Remember brakes??) Bortezomib (Velcade ) may be especially helpful in treating myeloma patients with kidney problems pamidronate (Aredia ) zoledronic acid (Zometa ) Stem cell transplant Lytic lesions or large tumors (plasmacytoma s) Becoming a go to RX for high risk disease or refractory disease. Is often a first line choice!! Surgery.rare Radiotherapy (I love RT!!!!) Chemo This Rx is not without significant risks and appropriate patient selection is critical.
7 Prostate Cancer Prostate cancer continues to be the most commonly diagnosed cancer among Canadian men. This year, an estimated that 23,600 men will be diagnosed with prostate cancer, and about 4,000 will die from the disease. Gleason Grades A grade given to prostate cancer on a scale of 1 5. The lower end of the scale indicates a low grade cancer, with 1 being extremely close to healthy prostate tissue. Grade 3 is the cellular pattern most often observed in prostate cancer. Gleason grade 5 tissue is very irregular and aggressive. Prostate cancer may display more than one class of Gleason grade. primary pattern the grade that comprises most of the tumour volume secondary pattern the grade that comprises less of the tumour. The composite number should be approached with caution, as there are many different ways to arrive at a Gleason score Eg Gleason 7 could be due to 3+4 or 4+3, the latter behaving more aggressively because the primary number is higher. The grades of the primary and secondary pattern are added together to create a composite called the Gleason Score, which can range from 2 to 10 (1 to to 5). 5 or 6 is not too bad 8 9 is terrible. (I haven t seen a 10)
8 PSA Free versus total PSA. the PSA test was originally approved by the FDA in 1986 to monitor the progression of prostate cancer in men who had already been diagnosed with the disease. In 1994, the FDA approved the use of the PSA test in conjunction with adigital rectal exam (DRE) to test asymptomatic men for prostate cancer. The amount of PSA in the blood that is free (not bound to other proteins) divided by the total amount of PSA (free plus bound). Some evidence (not a lot) suggests that a lower proportion of free PSA may be associated with more aggressive cancer. Pitfalls of trusting a PSA alone Some advisory groups now recommend against the use of the PSA test to screen for prostate cancer because the benefits, if any, are small and the harms can be substantial. (Cdn. Task force on prev. health 2014) None recommend its use without a detailed discussion of the pros and cons of using the test. Only 18% of men with an elevated PSA who go on to Bx have Prostate Ca. (ie. PSA can be up due to prostatitis or BPH) Some prostate Ca s Dx with an increased PSA and a Bx are so slow growing that Rx may actually have negative effects. recent studies have shown that some men with PSA levels below 4.0 ng/ml have prostate cancer and that many men with higher levels do not have prostate cancer Prostate CA Overtreatment exposes men unnecessarily to complications and harmful side effects of treatments for early prostate cancer, including surgery and radiation therapy. The side effects of these treatments include urinary incontinence, bowel dysfunction, erectile dysfunction infection, Etc.. The United States Preventive Services Task Force and the Canadian Task Force on Preventive Health have analyzed data and estimated that, for every 1,000 men ages 55 to 69 who are screened with a PSA every 1 to 4 years for a decade 0 to 1 death from prostate cancer would be avoided.
9 110 men would be diagnosed with prostate cancer. About 50 of these men would have a complication from treatment, including erectile dysfunction (29 men), urinary incontinence (18), serious cardiovascular events (2), deep vein thrombosis or pulmonary embolism (1), death due to the treatment in (<1). similar.) (American # s...cdn. Are The take home message then is Screen your patients and decide what, if any, benefit there is to Dx. the cancer. Remember, many docs, myself included, see prostate Ca as a disease of aging. This is going to be a tough sell esp. in Movember. Treatment Seven types of standard treatment are used: Watchful waiting or active surveillance Surgery Radiation therapy Hormone therapy Chemotherapy Biologic therapy Bisphosphonate therapy Hormone Therapy Removes hormones or blocks their action to stop cancer cells from growing. LH/RH agonists: prevent the testicles from making testosterone. Examples are leuprolide, goserelin, and buserelin. Antiandrogens. Examples are flutamide, bicalutamide, enzalutamide, and nilutamide.. (Prostate Ca has the coolest drug names in Oncology!!!).Drugs that prevent the adrenal glands from making androgens (ie. Ketoconazole) Estrogens: prevent the testicles from making testosterone. (Rarely used) Chemo Following a prostate ca pt. Way too many to mention. BUT ALL HAVE A FINITE EFFECT PERIOD!!! Biologics.same far too many to list. Bisphosphonates Decrease the number and activity of bone mets. Look for new symptoms: Urinary c/o New bony pain Weakness or other unexplainable c/o. (ie. Unilateral leg edema from lymph blockage.) If the PSA doubles in a six month period, the chances of developing metastatic symptoms go up significantly.
10 Remember According to the most recent data Prostate Ca can spread locally It can also metastasize usually to bone. (It s rare to see it metastasize to organs, but it can happen.) Relative 5 year survival rate is almost 100% The relative 10 year survival rate is 99% The 15 year relative survival rate is 94% Soooooo. What do we tell our patients????? I suspect we ll be asked to council extensively before any action is taken (This is going to be a major problem in a busy GP office ) (One of the MAJOR problems I have with the task force guidelines. It seems we ve been left hanging with less than thorough advice re management.) Italian Proverb Ovarian Cancer 3 main types of ovarian cancer. Bere bene fa bene Drink well be well Could be a NFLD motto Epithelial tumours. Serous carcinoma is the most common type. Stromal tumours. Granulosa cell tumours are the most common type. Germ cell tumours : These tumours are rare. Another rare type of ovarian cancer is extra ovarian primary peritoneal carcinoma. It is similar to epithelial ovarian carcinoma, but there is very little or no cancer in the ovary and it isn t clear where the cancer started.
11 It is estimated that in 2014: Risk factors for the development of ovarian cancer: family history of ovarian cancer: BRCA 1 and 2 genes result in a high risk for development of ovarian cancer. 2,700 Canadian women will be diagnosed with ovarian cancer and 1,750 will die. 1 in 72 Canadian women is expected to develop ovarian cancer during her lifetime and 1 in 93 will die from the cancer. A family history of breast or colon cancer Age: Women over 50 are more likely to get ovarian cancer. Childbearing and menstruation: Nulliparous women greater risk of developing ovarian cancer. In fact, the number of childbirths correlates directly with a decrease in risk for developing ovarian cancer. This seems to be related to the number of menstrual periods a women has had in her lifetime. Some studies show that women who have taken fertility drugs, or hormone therapy after menopause, may have a slightly increased risk of developing ovarian cancer. The use of oral contraceptive pills, on the other hand, seems to decrease a women's chance of getting the disease. obese women have a higher rate of ovarian cancer. possible early ovarian cancer symptoms include the following: Bloating Pelvic or abdominal pain Urgent or frequent urination Difficulty eating or early satiety Diagnosis Treatment Usually a biopsy involves a TAH/BSO (hell of a Bx!!!) Often advanced stage at diagnosis. Abdo/pelvic U/S CT abdo/pelvis RARELY.PAP (I ve seen 1 case but it is mentioned in the books!!) This, however is not definitive Rx. The initial surgery is usually followed by. Chemo (usually carboplatin/taxol (for the more common epithelial tumors)) x 3 cycles Then further surgery with node dissection, peritonectomy, appendectomy Then A further 3 cycles of chemo!!!!
12 CA125 Invasive epithelial ovarian cancer Relative 5 YearSurvival Stage I 90% IIA 78% III 39% IV 17% Ovarian stromal tumors Relative 5 yrsurvival RateI 95% II 78% III 65% IV 35% Usually elevated in Ovarian Ca s BUT a poor screening tool. Almost any intra abdominal inflammatory process will raise the CA 125. It is, however, a great tool for following patients post definitive Rx for Ovarian Ca. Risk of Recurrence An estimated 85% of patients with epithelial ovarian cancer who achieve a full remission following firstline therapy will develop recurrent disease. Each subsequent line of therapy is characterized by shorter disease free intervals median survival for these patients ranges from 12 months to 24 months. Chemo??RT?Further surgery. Recurrent Disease Please DO NOT tell women they are cured with first line Rx. I tell them they are in remission (hopefully permanent) and the average to recurrence can be anywhere from 6 months to 5 years. (Yes, it is sort of a fib!!) Following ovarian Ca (Easy to do at Year 1. They aren t so keen at year 4!!!!) Q 4 6 monthly labs including CA125 Physical exam, incl. PV and DRE CT s and U/S are not usually done routinely. (Please ask why not!!!) HOWEVER if the P/E is changing or CA125 go up, CT C/A/P Usually recurrence is local can get distant mets.
13 Ernest Hemmingway Foley s philosophy Always do sober what you said you d do drunk That will teach you to keep your mouth shut. Often wrong; never in doubt!!!!!!! Pancreatic Cancer 4% of cancers reported.(i think this # underestimates prevalence.) 2 Main types: #1: adenocarcinoma #2: Neuroendocrine. (That s the Steve Jobs type.) Pancreatic Cancer Minimal advance in Rx in the past 40 years. If surgery is not possible, treatment is considered palliative. Chemo is not overly effective, but can buy some patients some time, but often with significant morbidity. Usually causes a (very) high CA19.9 Often causes elevated liver enzymes..don t forget INR Chemo for Pancreatic Ca 3 main offerings. #1: gemcitabine usually very well tolerated. average survival benefit.about 4 months. #2: Folfori.5FU + irinotecan..more s/e but still not too bad. Average survival benefit 5 6 months #3: Folforinox.Average survival benefit..8 months. Major S/E profile. Very prone to blood clots Pancreatic Ca If the tumor invades the Celiac plexus pain +++. capture it early!!!!! And KEEP it captured!! Often seen with mets to the liver. May (often) causes biliary duct obstruction.. remember stents..v.v. effective
14 Stomach Cancer Stomach cancer is often reported as the 2nd leading cause of cancer death in the world. Infection with Helicobacter pylori increases the risk for stomach cancer by as much as 6x 1 in 20 stomach ulcers are cancerous. Only 1 in 5 stomach cancer patients will survive longer than 5 years. Types About 90 95% of stomach cancers are adenocarcinomas. About 4% of stomach cancers are gastric lymphomas. (MALT) About 3% of stomach cancers are gastrointestinal carcinoid tumours which start in the hormone secreting cells of the stomach. Gastrointestinal Stromal Tumour (GIST) A rare stomach cancer Males aged 80 to 89 have a 7 times greater risk of developing stomach cancer than they did in their fifties. Canadian females aged 80 to 89 have a 4 fold increased risk of developing stomach cancer than they did in their fifties. Overweight individuals have an increased risk for developing stomach cancer. Signs and Symptoms The use of tobacco may increase the risk of stomach cancer. Stomach cancer is more common in Asia, Southern and Eastern Europe, and South and Central America. AND IN NFLD!!! Eating a diet high in pickled, salted and smoked foods increases the risk of stomach cancer. Previous stomach surgery for benign disorders seems to increase the risk of cancer 15 or 20 years later. People with type A blood have a higher risk of getting stomach cancer. (Go figure!!) People who have a family history of stomach cancer are at an increased risk. Mild abdominal pain or discomfort made worse by food. Nausea or vomiting. Heartburn or indigestion. Loss of appetite. Difficulty swallowing. Fatigue or weakness. Unexplained weight loss. Early satiety..
15 Treatment Surgery offers the best chance of cure.. Over 50% of early stage cases of stomach cancer are curable Radiation therapy may be given to help with bleeding or pain Chemotherapy with 5 fluorouracil in combination with radiation therapy has recently been shown to improve survival in people who have had their tumour completely resected. Chemotherapy alone is sometimes helpful, but it will not cure stomach cancer. Stage IA 71% Stage IB 57% Stage IIA 46% Stage IIB 33% Stage IIIA 20% Stage IIIB 14% Stage IIIC 9% Stage IV 4% 5 year survival MALT Tumors High assoc. with H. pylori Can often Rx with H.Pylori eradication and PPI s Recurrences can be Rx by repeating H. pylori Rx DVT/PE Tidbits of info Cancer is a hypercoaguable disease. DVT is a huge risk, the third biggest killer in oncology patients. #1: disease progression #2: infections Always be leery of potential clots!! They can occur in non common sites such as SVC, axillary veins.among others Rx is LMWH warfarin is only 50% as effective as LMWH in oncologic disease.
16 DVT/PE Rx with LMWH for 3 6 months post disease clearance or for life in malignant disease. (May stop for palliative intent..) Brain, pancreas, lymphoma and mucin secreting tumors are especially bad when it comes to clots. Steroids Can be enormously helpful for quick symptom control in a number of situations. Especially helpful with symptom control with lymphomas and brain mets and post RT. I normally use dexamethasone, but prednisone is a good choice. Dex. is 7 10x more potent than prednisone. Steroids Hint Dosing is controversial..i usually don t go above 16 mg dexamethasone and taper down after 2 3 days to 12, 8 then 4mg as indicated by effect. Hematologists like higher doses. Neurosurgeons go nuts with Dex.(If it wasn t generic, I d think they had stocks in the company!!) If there is good effect, taper by pt. response, not a predetermined schedule. If a patient has bulky or metastatic disease (even brain mets) a trial of steroids is a good idea. You may not see this in print, but a poor response to steroids often indicates a poor response to RT. Remember. Steroids are used as an OD, BID or TID medication. Drug half life is approx. 4 hours but the biologic half life is hours.. I, therefore, use it as a OD med. Long term steroid use causes the same symptoms you started the steroids for (Tsk, tsk.ending a sentence with a preposition Dad is spinning in his grave.. ) Please Rx for AM use to hopefully mitigate late day agitation and sleep disturbance.
17 Blockages In some situations stents are very helpful.if available. Examples would include biliary, SVC, rectal, esophageal, bronchial Really useful with pancreatic Ca s for obstructed ducts. (I strongly believe this dramatically affects survival in a positive way!!) Radiation Therapy Used as neo adjuvant, adjuvant, post chemo or Palliative Rx Some basic facts #1: RT s use cgy s (centi Grays).units of radiation cGy is often palliative dose basic Rx > 4500 is a BIG dose!!!! (may go up to 8000 cgy..) RT Fractionation means the dose is spread out over time.. ( e.g cGy in 10 fractions) Great Rx for bony mets Brain RT well tolerated Solid tumors need higher doses There is a flare effect often seen after RT. (Usually at days.) Symptoms may worsen during this time. Warn the patients, they think it s the cancer worsening!!! Steroids are an excellent prophylactic for this. Eg. 8,6,4,2mg over a week or so.. Albumin Chemotherapy My favorite blood test (for prognosis!!!) Low levels in cancer patients POOR prognosis (This is anecdotal.but I firmly believe it!!) Screws up Calcium testing remember to correct..and.check Magnesium with the Ca+. 1 st line Rx is almost always the best RX. Effectiveness decreases as you advance through chemo lines. Patients have a rough time accepting the FACT that we DO run out of effective therapies.
18 Chemotherapy If an oncologist says There s a 20% response rate..the patient often hears cure or that there is an indefinite duration of disease control. Always ask the next question.. For how long??? The answer is often weeks. Evaluations??????????????????????? Please complete..i need to know if these talks are of any use!!!!!!!! Josh And.Thanks for listening!!!!!!!!!! T.S.Eliot W.C. Fields Birth, and copulation, and death. That s all the facts when you come to brass tacks. After two days in hospital I took a turn for the nurse.
19 Leigh Stoecker Danish Proverb If your time ain t come not even a doctor can kill you. He who makes no mistakes, does nothing