Cancer information Cancer treatment

Ovarian Cancer. Screening

One of the most significant ways to improve survival for patients with ovarian cancer would be to find a way to screen women for ovarian cancer and detect the disease before it spreads beyond the ovary. Currently available methods for screening for ovarian cancer are pelvic examination, serum CA 125 level measurements, and pelvic or transvaginal ultrasonography. To date, there is no evidence that routine pelvic examination is effective in the early diagnosis of ovarian cancer. Serum CA 125 levels have also shown to be ineffective because of the high false-negative rates. A review of the literature found that only about 50% of patients with stage I ovarian cancer have an abnormal serum CA 125 level. To substantiate this point further, the only study to look at CA 125 screening for ovarian cancer reported that in the six cancers of the ovary diagnosed by CA 125 screening, four had spread beyond the ovary. However, in three studies, pelvic or transvaginal ultrasonography screenings of 7,576 patients diagnosed 10 cancers, all stage I. Unfortunately, this technique has a high false-positive rate, and between 13 and 65 patients underwent surgical exploration for each cancer detected in these studies. If some additional test could be discovered that would allow determination of which patient with an enlarged ovary actually needs exploration, transvaginal ultrasonography might turn out to be an effective screening tool. Current research in this area centers around developing a more precise morphology index, a more specific color flow Doppler pattern, and more specific serum markers.

TABLE 6. Stage at Diagnosis and 5-Year Survival Rate of Gynecologic Cancers, United States 2006

Stage at Diagnosis (%) 5-Year Survival Rate (%)

Site Localized Regional Distant Localized Regional Distant

Endometrium 73 13 10 96 69 28

Cervix 51 33 8 92 52 10

Ovary 23 15 56 91 49 23

Ovarian Cancer. EPIDEMIOLOGY AND DIAGNOSIS

About 26,800 women are diagnosed with ovarian cancer each year in the United States. Of these women, approximately 14,200 will die of the disease. Ovarian cancer represents 55% of all deaths from gynecologic cancer. The risk of a woman developing ovarian cancer during her lifetime is 1-2%. The incidence varies with age and is 1.4 per 100,000 in women under age 40 years and 38 per 100,000 in women older than age 60 years. Figure 4 illustrates the prevalence of different types of ovarian cancer by age. Ovarian cancer is more common in Northern European and North American countries than in Asia, developing countries, or southern continents.
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The etiology of ovarian cancer is not known, but risk factors include infertility, low parity, or both; use of talc on the perineum; high-fat diet; lactose intolerance; history of breast or colon cancer; and a family history of ovarian cancer. Smoking, alcohol use, coffee consumption, estrogen replacement therapy, and viral infections (such as mumps) have not been associated with increased risk. Use of oral contraceptives, however, is protective for ovarian cancer, with an average relative risk of about 0.7 for women who have used oral contraceptives for 2 years and a 0.5 relative risk for women who have used oral contraceptives for 5 years or more. The protective effect of oral contraceptive use appears to be long term, with some studies indicating a lifetime risk reduction.

Table 6 illustrates the relative stage at diagnosis and the survival by stage for ovarian cancer in relation to other gynecologic cancers. The 5-year survival rate for ovarian cancer by stage is not significantly different from the 5-year survival rate for other gynecologic cancers; however, there is a significant difference in stages, with ovarian cancer usually having spread into the abdomen in about two thirds of patients at the time of diagnosis. It is clear from these data that the single most important factor in the large number of deaths from ovarian cancer is the failure to diagnosis the disease at an early stage. The reasons for this failure correspond to the growth and spread patterns of the disease. Because the ovary floats freely in the pelvic cavity, a tumor can grow for some time without producing symptoms associated with involvement of, or pressure on, other organs.

Lung Cancer. Part 6

We should culture quickly and start on some appropriate form of broad spectrum antibiotics. This should be continued until the granulocyte recovery takes place. And granulocyte recovery used to be defined by achieving an absolute number. I think we can substitute for that granulocyte count is increasing on two or three successive days. I think we know that the granulocyte count is rising even if it’s only 500 you are making granulocyte counts, and remember what you see in the peripheral blood is the reserve. It’s what is left over after the granulocytes are mobilized. So I won’t feel quite comfortable for a patient who is doing well with granulocyte count that is going from 89 to 150 to 230 over three successive days, even though they are not at 500. That person is on the way up and if they don’t have a demonstrated site of infection that requires continued antibiotics appropriate for that infection, if nothing else has been cultured – and that’s usually what happens – nothing astounding in the culture, I think you can stop antibiotics safely at that point. Obviously if they have a positive culture or a demonstrated site of infection you need to give a course of therapy which is appropriate for that site of infection.

If you have cancer patients who have a fever and the granulocyte count is at a healthy level and is not falling rapidly, these patients could be managed like anybody else with a fever who comes for medical attention. Keep in mind that patients with cancer may have fevers as a result of drugs. Bleomycin, for example, they may have fevers as a result of the underlying disease, including lymphomas and renal cell cancers with liver metastases, or they may have reactions to blood products. Large differential. But you can walk not run to the nearest exit the situation if the granulocyte count is in good range.
Lung cancer

Lung Cancer. Part 5

You see also all the time it crops up in board management questions from time to time; someone who has had a malignancy that has been managed for cure – let’s say a small breast cancer or colon cancer – and has the appropriate response and in three or five years later develops a pulmonary nodule. Don’t assume ever that that’s a metastasis from a previously treated, presumed cured, malignancy. In the case of breast cancer, which is my own area of specialty and the area that I know the best, I know that over half of pulmonary nodules that present in patients with prior breast cancers are unrelated to the prior breast cancer. So again, histologic class clarification is generally the way to go in these situations.

This is some data from the Mayo Clinic that just shows what happens if you operate on coin lesions. You remember how dismal the data was when I showed you, in general, for surgery in lung cancer but these are coin lesions specifically. If you look at small coin lesions that were operated on and have no nodal involvement, the surgical survival is much better than the data I showed you in lung cancer overall. So there’s real reward in operating on these small peripheral coin lesions. So you don’t want to ignore them and you want to get a pathologic diagnosis in virtually every situation.
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Fever in the setting of malignancy. The most important thing about fever in cancer patients is; what is the granulocyte count. If the granulocyte count is 500 granulocytes per cubic millimeter, or is the white count rapidly falling. For example, in patients who have a white count of 4,000 two days ago, white count of 2,000 yesterday and a white count of 1,000 today, even if the granulocyte count may be at 600 that patient is in some sort of granulocyte free-fall and is usually the result of chemotherapy. You can expect that that patient has no granulocyte reserve for falling rapidly. So the absolute number of about 500 or expend of rapid decrease is when you really have to worry and take extra precautions for these patients. If you have a patient like this they need to be seen in an emergency room setting, they need to be cultured very quickly, fully and very quickly. You get your cultures sent off in 30 minutes or an hour – not more than that – and then the patient should receive broad-spectrum antibiotics. Even if you identify a potential source of infection – let’s say they are coughing up sputum that looks infected – they must be covered broadly because many of these patients will have more than one potential source of infection. So infected sputum or an abnormal intravenous catheter site may not be all that patient is dealing with. So the watch-word is to cover the patient broadly with antibiotics and give them monotherapy with something like ceftazidime. There’s even some literature recently about using Cipro in the outpatient setting. But you have to be careful.

Lung Cancer. Part 4

In terms of the management, we have developed increasingly better drug and radiotherapy combinations for dealing with this. Patients who have disease which is limited in presentation, clinically limited to the ipsilateral hemithorax. That is we don’t have clinical evidence of spread even though it’s thought to be there microscopically, about half of these patients will be able to go into complete remission and the overall remission duration for these patients is somewhere on the order of 15 to 20 months. If you look at a survival curve for small cell lung cancer, if you look at those with overt metastases, results are extremely poor. On the other hand, if you look at patients who have disease which is limited – as I said, clinically – to the ipsilateral hemithorax, somewhere around 20% of these patients seem to go into remission that may be durable and some of these patients may be cured of the disease. What is being looked at for these patients is; can we do anything to get the tail on the curve up a little bit. Can we do something to increase the fraction of patients with complete remission rates. Can we do something to keep these patients in remission instead of having this fall-off. Intensive therapy with stem-cell support is being looked at. There is pilot data from Elias and Ferguson that looks pretty good, but it needs to be reproduced in a larger group setting. Also it is important to understand the theory for this as considerable morbidity and even mortality, the use of intensive drugs and radiation in middle-aged or older adults who often have significant underlying pulmonary disease that has led to a lot of respiratory complications, their central nervous system, complications from prophylactic brain radiation and drug therapy. So there’s no free lunch. It’s difficult therapy and there are significant long range morbidities from the treatment but the good news is that at least a proportion of patients with limited disease are able to achieve a disease-free survival from this naturally pretty aggressive condition.
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I think you can’t leave the subject of lung cancer when talking to internists without talking about the pulmonary nodule. This is sort of a common internal medicine management problem. These are some of the things I think that should be tried in dealing with this. First of all what you want to know if there is a pulmonary nodule is; is the lesion new? And if the lesion is not new, has it changed in size? So the first thing you want to do is obtain old films. I think that today management strategies for medicine, the less people have chest x-rays on a routine basis and that may hamper making that sort of assessment. But where old films are available I think management always starts with getting the old film. If you can get some archival film from ten years ago that shows the same lesion I think you are going to have almost certainly no problem. The next step is if there is a nodule and it appears to be new, or we don’t have an old film, we need to know; is it solitary or multiple? The decision analysis will be different if you have multiple lesions. Remember, chest x-ray is a lot less sensitive than a CT in terms of showing the lung parenchyma. So what looks like a solitary lesion on a chest x-ray could turn out to be multiple lesions on a CT-scan. Once we have characterized what we have, you are going to undergo some type of pre-biopsy or pre-surgical evaluation to look at extrapulmonary sources that need to be ruled out. It doesn’t have to be exhaustive. A good history and physical and maybe a minimal amount of laboratory testing is probably useful in this setting. If the studies are negative or you don’t demonstrate conclusively that this is a metastatic presentation of some other lesion, then it is necessary to go after this thing and clarify what it is. Many of these lesions have proved to be benign lesions and even if it does prove to be an adenocarcinoma presenting as a lung lesion, the prognosis of this is relatively favorable, quite favorable indeed compared to other forms of carcinoma of the lung that are resected. No meat no treat is a good rule to follow. Don’t make assumptions based on the x-ray getting a pathologic diagnosis.

Lung Cancer. Part 3

In stage IV lung cancer, for metastatic disease, again there has been some debate. We have gone through probably 20 or 25 years of trying chemotherapy in this disease and until fairly recently the results were dismal. Colleagues at the Princess Margaret _ study in Canada where they looked at chemotherapy versus supportive therapy only for stage IV lung cancer. I think being a very conservative group their bias was that supportive care was probably going to be better than flogging patients with chemotherapy. Much to their surprise they found out that the group of patients with metastatic non small cell lung cancer received chemotherapy not only got an improvement in survival but also an improvement in quality of life as assessed by the patients, and actually a somewhat lower cost for care for patients who were given supportive care only. I think that chemotherapy has improved a lot for lung cancer. The standard regimens often involve a taxine usually, Taxol and some kind of platinum derivative such as carboplatin. I think we are getting response rates that are high enough to justify chemotherapy for patients who at least have a good performance status for advanced lung cancer. Now patients who are very terribly ill or bedridden with marked constitutional symptoms are probably not the type of patients who are going to benefit from this type of intervention but a relatively good-health patient with advanced disease is likely to benefit in all of these ways from chemotherapy.

This is small cell carcinoma, which as I said is a different disease. This is the pulmonary bronchial epithelium at the basement membrane. This is small cell cancer smudged in here inside mucosa. Small cell cancer is usually advanced at the time that the diagnosis is made. It is at least advanced microscopically. If you can’t find it, I think this slide shows part of the problem. One part is because it is submucosal that the early signs of cough or hemoptysis are often not present. It also has a very high growth fraction, as it has an early capacity to spread and lacks early warning signs to focus a patient or physician towards a diagnostic work-up. So we think of all patients with small cell cancers essentially as having disseminated disease at the time they are diagnoses. You remember the slide I showed you a few back – it showed the surgical cure rate for this disease is under 1%. I think that that feeds into what I’ve been saying about our thinking that we really consider this to be disseminated. The only difference is you can subdivide them into those that are overtly disseminated and those where you can’t find evidence of it but you know it’s there.