Archive for the Ovarian Cancer category.
Then the issue of the biology of cancers is important. Is there a difference in the intrinsic biology of the distal intestinal metaplasia-type cancers and the more proximum Barrett’s type of thing? That’s important. There’s a blur between, nowadays, between esophageal and gastric cancer. Order Propecia 5 mg online at licensed canadian pharmacy. The distal adenocarcinomas of the esophagus and the proximal gastric cancers really get into the same protocols, are probably very much the same disease. Then what type of surgery? We talked about this relatively exhaustively. I think what we know now is that across the board it doesn’t appear, there isn’t data, that doing a D2 dissection will result in improved survival. I have effective adjuvant therapy, for example radiation and chemotherapy, does the performance of the D2 dissection obviate the need for postoperative therapy? I think you will see, when you hear about rectal cancer later today, that’s a very interesting question there because of this total mesorectal excision which is a very careful, meticulous excision of the rectum, developing surgical planes. The data reported from that show the relapse rate is much lower if you do that than if you do the typical resection. It may be that patients with TME’s, total mesorectal excisions, you don’t need postoperative radiation therapy. Phase III trials are obviously the way to go.
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I can show you a little bit about neoadjuvant therapy because the next clinical trial in gastric cancer, the intergroup gastric study, will be a neoadjuvant therapy study. This is an older study and I show it to you because it is a good example of what’s been done in neoadjuvant therapy. This was a study done in Germany and what they did was they took patients to laparotomy and they did determine that they were non-resectable. They treated them with a regimen that we don’t do anymore – etoposide, Adriamycin, platinum – because it’s a little bit toxic. If they didn’t respond they were off study. If the patients responded either with a clinical complete response or a clinical partial response, they went to second look operation. Non-resectable, they were off study. If they were resectable they were resected to achieve no evidence of disease and these were pathologic clinical responses or they rendered no evidence of disease, and then they received chemotherapy afterwards. What was seen in 33 patients from Hans Joachim Wilke and colleagues at Essen was that there was a complete clinical response. In other words, no evidence of tumor at the time of surgery in 21% of them, and there was no evidence of tumor pathologically in 5 of the 33 patients. They were able to take essentially two-thirds of the patients who were un-resectable and resect them. There was a high relapse rate of about 60% after some 20 months of follow-up. Most of these relapses were local, which means that perhaps if you had added postoperative radiation therapy or done something particularly innovative – like maybe intraperitoneal therapy or perhaps intraoperative radiation therapy – one could decrease the local relapse rate. But anyway, these are the sorts of data that are seen so it appears that neoadjuvant therapy is effective in causing a tumor to shrink down. The question that hasn’t been addressed in randomized fashion is, is it indeed – when you look at all the patient selection factors – is it indeed per primum surgical therapy? The next study we will do in the intergroup is just that. Is neoadjuvant therapy versus standard resection followed by radiation chemotherapy, if that has shown in the last study to be the effective postoperative adjuvant.
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You are going to see actually, in the esophageal presentation, David Kelson’s study which was published in the New England Journal about December of last year, which was a randomized study of 5FU/platinum in patients with esophageal cancer. Very nice preoperative study that was an appropriate phase III study. Now these are kind of dangerous but interesting data. These are data from the German group that were presented at one of the Tucson adjuvant meetings about four years ago, four or five years ago. What they did is they looked at their patients who were resected for cure after neoadjuvant therapy, looked at their survival, versus patients who never received neoadjuvant therapy but were resected for cure. You can see that these patients appear to do better, and these curves were significant. The conclusion that one could draw is that neoadjuvant therapy is better. However, the danger here in interpreting these data is that of course this is not a randomized study. These are historical controls, and to get to neoadjuvant therapy – to get through the neoadjuvant therapy, to get to the second operation to get resected – requires patients to go through all sorts of hoops, and these patients may just actually be better protoplasm. They may have more indolent tumors. There may be a variety of things that need to be answered in a randomized study. But when you do look at patients who have had neoadjuvant therapy and have been resected, generally across the board, stage for stage, they do better than historical controls.
The fallopian tube is the least common site of gynecologic cancer in females, accounting for fewer than 1,000 new cases each year. Histologically, these tumors resemble papillary serous carcinoma of the ovary in more than 90% of cases. Diagnostic criteria for primary fallopian tube carcinoma include the following:
• The main tumor is in the tube and arises from the endosalpinx.
• The pattern histologically reproduces the epithelium of the mucosa and usually shows a papillary pattern.
• If the wall is involved, the transition between benign and malignant tubal epithelium should be demonstrable.
• The ovaries and endometrium are either normal or contain less tumor than the tubes.
The major concern is to distinguish these cancers from primary ovarian cancers. The staging system used for fallopian tube cancer is modified from the staging system for ovarian cancer because there is no FIGO-established official staging system for fallopian tube cancer.
Fallopian tube cancer and ovarian cancer spread in a similar manner. The classic triad of colicky pain, abnormal bleeding, and leukorrhea is rarely seen in its entirety; the most common symptom is abnormal vaginal bleeding. Pain, however, is reported frequently as an early symptom.
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The therapy of fallopian tube cancer is similar to the therapy of ovarian cancer; the most important initial therapy is effective cytoreductive surgery. As in ovarian cancer, residual disease is a good predictor of survival rates. The adjuvant therapy of choice is chemotherapy with platinum-based multidrug therapy, followed by a second-look laparotomy and second-line therapy as necessary. There are no reports of the use of paclitaxel in fallopian tube cancer, but one would surmise that this drug will have a significant role in the therapy of the disease.
Sex cord-stromal or sex cord-mesenchymal tumors include tumors of the female type (granulosa cell tumors and granulosa-theca cell tumors), the male type (Sertoli-Leydig tumors), and very rare types such as lipid cell tumors and gynandroblastoma. The majority of these rare tumors will never be seen by the practicing gynecologist.
Ovarian cancer
The granulosa cell tumor is the most common malignant tumor of this group of neoplasms. As shown in Figure 4, these tumors occur throughout a woman’s lifetime but are more common in the first four decades. They are bilateral in only about 5% of cases. All granulosa cell tumors should be considered potentially malignant, and late recurrences are common. There are two major histologic types: the adult variety and the juvenile form. The juvenile form is much more likely to result in a malignancy.
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The therapy of granulosa cell tumors is surgical removal; there is no proven benefit for adjunctive therapy. In younger patients who desire to retain their childbearing capability, unilateral salpingo-oophorectomy and full surgical staging are the treatment of choice. Patients with residual or recurrent disease should receive chemotherapy. The usual choice of chemotherapy is bleomycin, etoposide, and platinum, as it is in germ cell tumors. There are too few reported series of granulosa cell tumors treated with chemotherapy to provide accurate figures on response rates to chemotherapy.
Cancer treatment
Young patients with granulosa cell tumors may show precocious puberty because these tumors may produce estrogen. In older women, menstrual irregularity or post-menopausal bleeding due to estrogen production may be the presenting symptom.
Sertoli-Leydig tumors occur less frequently than granulosa cell tumors and are rarely bilateral. These tumors may produce androgens and can present clinically with defeminization or masculinization. The malignant potential of these tumors is directly related to the degree of differentiation, and they are usually classified as well differentiated, moderately differentiated, or poorly differentiated. A fourth classification is Sertoli-Leydig tumors with heterologous elements.
The treatment for these tumors is surgical removal, and unilateral salpingo-oophorectomy is indicated for patients with properly staged disease and tumors confined to one ovary. Little is known about the responsiveness of these tumors to chemotherapy, but most authors recommend bleomycin, etoposide, and platinum chemotherapy for persistent or recurrent disease.
Other stromal tumors are very rare. In general, the therapy is total abdominal hysterectomy and bilateral salpingo-oophorectomy, with full surgical staging for patients who do not desire further childbearing. For younger patients, unilateral salpingo-oophorectomy and full surgical staging are indicated.
TABLE 14. Adjuvant Chemotherapy for Stage I and Completely Resected Stage II and III Malignant Germ
Cell Tumors*
Institution Regimen No. Progression Free % of Total
GOG BEP 50 of 52 96
Stanford PVB 5 of 5 100
Cross Cancer Institute PVB 4 of 4 100
MD Anderson Cancer Center PVB 4 of 4 100
MD Anderson Cancer Center BEP 20 of 20 100
Total 83 of 85 98
*GOG indicates Gynecologic Oncology Group; BEP, cisplatin-etoposide-bleomycin combination; PVB, cisplatin-vinblastine-bleomycin combination.
Modified from Williams SD, Gershenson DM. Management of germ cell tumors of the ovary. In: Markman M, Hoskins WJ, eds. Cancer of the ovary. New York: Raven Press, 1993
TABLE 15. Chemotherapy of Patients with Incompletely Resected, Persistent, or Recurrent Malignant Germ
Cell Tumors*
Institution Regimen No. Prognosis Free % of Total
GOG PVB 47 of 89 53
Stanford PVB 4 of 4 100
Cross Cancer Institute PVB 8 of 10 80
MD Anderson Cancer Center PVB 7 of 11 64
MD Anderson Cancer Center BEP 5 of 6 83
Total 71 of 120 59
*GOG indicates Gynecologic Oncology Group; PVB, cisplatin-vinblastine-bleomycin combination; BEP, cisplatin-etoposide-bleomycin combination.
Modified from Williams SD, Gershenson DM. Management of germ cell tumors of the ovary. In: Markman M, Hoskins WJ, eds. Cancer of the ovary. New York: Raven Press, 1993
Survival is enhanced by complete cytoreduction of malignant germ cell tumors. Every effort should be made to resect the disease completely, but there is no need to remove reproductive organs not involved with the cancer. These tumors are virtually never bilateral. Thus, even patients with advanced disease who do not have involvement of the other ovary and the uterus should have those organs conserved. Because high cure rates are achieved with the use of multidrug chemotherapy, many patients will retain their reproductive capability.
Patients with malignant germ cell tumors of the ovary should undergo surgical staging similar to that for epithelial ovarian cancer. However, because most patients will require chemotherapy, reexploration for staging is not indicated unless the goal is to resect residual cancer completely. It is best to begin chemotherapy as soon as possible because tumors recur and grow rapidly.
The potential benefit of second-look laparotomy has been debated for several years. Recently, no benefit was found for second-look laparotomy except in incompletely resected immature teratomas, and its routine use in other malignant germ cell tumors cannot be justified.
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Malignant germ cell tumors of the ovary occur primarily in the second and third decades of life, although they are occasionally found in young girls and older women. The tumors are usually accompanied by abdominal pain, and almost 10% of patients will present with an acute episode of torsion, hemorrhage, or rupture of the tumor.
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Germ cell tumors may be associated with elevated serum levels of the beta subunit of human chorionic gonadotropin (b-hCG), alpha-fetoprotein, or lactic dehydrogenase. Measurement of these markers may aid in the diagnosis of germ cell tumors and may be useful in management and follow-up care. Serum markers are shown in Table 13. There is considerable variation in markers, although most endodermal sinus tumors produce alpha-fetoprotein, and most choriocarcinomas and dysgerminomas produce b-hCG and lactic dehydrogenase, respectively.
TABLE 13. Serum Markers in Malignant Germ Cell Tumors of the Ovary*
Serum Marker
Malignant Germ Cell Tumor AFP b-hCG LDH CA 125
Endodermal sinus tumor + – + +
Embryonal carcinoma + + + +
Choriocarcinoma – + + +
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Immature teratoma + – + +
Dysgerminoma – + ± ±
Mixed germ cell tumor ± ± ± ±
*AFP indicates alpha-fetoprotein; b-hCG, beta subunit of human chorionic gonadotropin; LDH, lactic dehydrogenase. t Marker depends on the type of germ cell tumors present.
Cancer treatment
Prognosis is good for most patients treated with platinum-based multidrug chemotherapy. Table 14 displays the results of adjuvant chemotherapy in stage I and completely resected stage II and stage III patients with malignant germ cell tumors. Of 85 patients given adjunctive therapy of either bleomycin, etoposide, and platinum or platinum, vinblastine, and bleomycin, 83 (98%) were progression free. In comparison, patients who had residual disease, had persistent disease, or developed recurrences had a progression-free survival rate of only 59% (71/120 patients) when treated with similar regimens (Table 15).
Patients with early-stage ovarian cancer usually have a low recurrence rate, providing they had full surgical staging and received appropriate therapy. Exceptions include patients with clear-cell cancers of the ovary. Because of the low recurrence rate, patients should be followed with a gynecologic examination and a serum CA 125 test every 3 months for the first year, every 4 months for the second year, and every 6 months for the next 3 years. After 5 years, annual examinations are recommended. Annual Pap tests are recommended. There is no proven benefit of diagnostic radiography and computed tomography in asymptomatic patients with a normal serum CA 125 level.
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Patients with advanced ovarian cancer have a very high recurrence rate, approaching 75% after a complete clinical response and 50% after a complete pathologic response (negative second-look laparotomy). For these patients, follow-up should be more intensive. They should have a gynecologic examination and a serum CA 125 test every 3 months for the first 2 years. Follow-up at 6-month intervals is recommended for the next 3 years. The use of routine computed tomographic scans is debatable, although many experts recommend scans for follow-up of patients who did not have a second-look laparotomy. The optimum frequency for such scans has not been established.
The value of the serum CA 125 test in the follow-up of patients depends in large part on whether the patient had an elevated serum level before therapy, even though CA 125 levels do not always correlate with tumor volume. The serum test does, however, appear to be the best follow-up test available.