ir a principal |
Ir a lateral
- Stage I - limited to one or both ovaries
- IA - involves one ovary; capsule intact; no tumor on ovarian surface; no malignant cells in ascites or peritoneal washings
- IB - involves both ovaries; capsule intact; no tumor on ovarian surface; negative washings
- IC - tumor limited to ovaries with any of the following: capsule ruptured, tumor on ovarian surface, positive washings
- Stage II - pelvic extension or implants
- IIA - extension or implants onto uterus or fallopian tube; negative washings
- IIB - extension or implants onto other pelvic structures; negative washings
- IIC - pelvic extension or implants with positive peritoneal washings
- Stage III - microscopic peritoneal implants outside of the pelvis; or limited to the pelvis with extension to the small bowel or omentum
- IIIA - microscopic peritoneal metastases beyond pelvis
- IIIB - macroscopic peritoneal metastases beyond pelvis less than 2 cm in size
- IIIC - peritoneal metastases beyond pelvis > 2 cm or lymph node metastases (retroperitoneal or inguinal)
- Stage IV - distant metastases to the liver or outside the peritoneal cavity
- Note: Liver capsule metastasis T3/Stage III; liver parenchymal metastasis M1/Stage IV.
Pleural effusion must have positive cytology for M1/Stage IV.
Testicular cancer survivors who were treated with chemotherapy, radiotherapy or both have increased long-term risks for cardiovascular disease, a new study found.
Because such cancers are usually diagnosed before age 40, survivors can live several decades after treatment and doctors should watch for complications, the researchers note in their paper published online September 20th in the Journal of Clinical Oncology.
The lifelong follow-up for these men should focus on their cardiovascular risk profile and lifestyle interventions to prevent cardiovascular disease, lead author Dr. Hege Haugnes, of the University of Tromso, Norway, told Reuters Health in an email.
Dr. Haugnes' team studied 990 men treated for unilateral testicular cancer, following them for a median of 19 years. They stratified the men into four groups according to their treatment: 206 who had surgery only, 386 who had radiotherapy, 364 who had chemotherapy, and 34 who had both radiation and chemotherapy.
Compared to the surgery group, there was a higher risk for diabetes in men treated with radiotherapy alone (odds ratio: 2.3) or the combination of radiotherapy and chemotherapy (OR: 3.9).
The authors also found that 74 men (8%) developed atherosclerotic disease during follow up. Cox regression analysis showed increased hazard ratios for atherosclerosis after all cytotoxic treatments compared with surgery only (radiotherapy, HR 2.3; chemotherapy, HR: 2.6; both, HR 4.8).
Most chemotherapy was cisplatin-based, combined with bleomycin and either etoposide or vinblastine. When the researchers analyzed the men according to their treatments, etoposide was linked with a 5.7-fold higher risk for coronary artery disease and a 4.7-fold higher risk for atherosclerotic disease compared to surgery.
Compared to a separate group of matched controls, patients who received etoposide had a significantly higher risk of myocardial infarction (HR, 3.1) as did those in the combination therapy group (HR, 4.8).
Except for the etoposide results, previous studies had shown similar patterns, Dr. Haugnes said. She called the etoposide findings the most surprising in the study.
"A possible bias here is the inclusion of living men only, and thus only cardiovascular disease morbidity and not mortality has been reported," she said.
Patients with either saline- or silicone gel–filled breast implants may have a very small but significant risk for a rare cancer called anaplastic large-cell lymphoma (ALCL) adjacent to the implant, the US Food and Drug Administration (FDA) announced today.
While the agency continues to investigate the possible association between ALCL and breast implants, it is advising clinicians to consider the possibility of the cancer in patients with breast implants with late onset of fluid build-up called persistent peri-implant seroma. Clinicians also should report any confirmed cases of ALCL in women with breast implants to the FDA.
The agency is advising women with breast implants not to change their routine medical care and follow-up. Because the risk for ALCL appears to be very small, the agency believes the weight of evidence "supports a reasonable assurance that FDA-approved breast implants are safe and effective when used as labeled."
A rare cancer of the immune system that can occur anywhere in the body, ALCL is diagnosed in 1 of every 500,000 women per year in the United States. ALCL in the breast is rarer still, diagnosed annually in roughly 3 of every 100 million women without implants. In women with breast implants, it is usually inside the fibrous scar tissue — called a capsule — surrounding the implant. It is not a cancer of the breast per se.
Treatment options for ALCL are chemotherapy, radiation, and surgery, said William Maisel, MD, MPH, chief scientist and deputy director for science in the FDA's Center for Devices and Radiological Health, at a press conference today. The evidence suggests that the kind of ALCL found in conjunction with breast implants is less aggressive and is sometimes treatable by simply removing the implant, the capsule, and collected fluid, according to Dr. Maisel.
An FDA review of scientific literature published from January 1997 through May 2010 uncovered 34 unique cases of ALCL in women with breast implants throughout the world. The agency is aware of 60 cases in all, some of them identified through other channels. The FDA does not know how many of the 60 may be duplicates of cases found in the literature. An estimated 5 million to 10 million women worldwide have received breast implants, according to the FDA.
Of the 31 published cases of ALCL, 24 involved silicone implants, and 7 saline implants. The median time from implant to ALCL diagnosis was 8 years. For most of the women, the cancer was diagnosed when they sought treatment for implant-related symptoms, such as pain, lumps, swelling, or asymmetry, after their surgical sites had healed. These symptoms result from persistent peri-implant seroma, hardening of the breast area around the implant, or masses surrounding the implant.
Plastic Surgeons and FDA Will Develop Patient Registry
The vast majority of data suggesting a link between ALCL and breast implants emerged only after the FDA approved silicone gel breast implants made by Allergan and Mentor in 2006, said Dr. Maisel. From 1992 to 2006, such silicone gel implants were available only on an investigational basis.
Dr. Maisel noted that silicone from ruptured and even intact implants has been found in nearby breast tissue. According to one theory about the origins of ALCL, this silicone chronically stimulates immune system T cells and induces lymphoma.
"Please understand that is speculative, and a hypothesis," said Dr. Maisel.
To get to firmer scientific ground, the FDA will collaborate with the American Society of Plastic Surgeons and other groups to develop a registry to collect more information that would better characterize ALCL in women with breast implants. The agency also is asking implant manufacturers to report ALCL cases. And for the sake of patient and clinician education, the FDA will work with these manufacturers to update product labeling materials.
More information about today's announcement is available on the FDA Web site. The FDA's preliminary findings and analyses are available here.
TUMOR
TX: The primary tumor cannot be evaluated.
T0: There is no evidence of a tumor in the prostate.
T1: The tumor cannot be felt during the DRE and is not seen during imaging (any test that produces pictures of the inside of the body, such as a CT scan). It may be found when surgery is done for another reason, usually for BPH, or abnormal growth of benign prostate cells.
T1a: The tumor is in 5% or less of the prostate tissue removed through surgery.
T1b: The tumor is in more than 5% of the prostate tissue removed through surgery.
T1c: The tumor is found during a needle biopsy, usually because the patient has an elevated PSA level.
T2: The tumor is found only within the prostate, not other areas of the body. It is large enough to be felt during the DRE.
T2a: The tumor has invaded one-half of one lobe (part or side) of the prostate.
T2b: The tumor has spread to more than one-half of one lobe of the prostate, but not to both lobes.
T2c: The tumor has invaded both lobes of the prostate.
T3: The tumor has grown through the prostate capsule (into the tissue just outside the prostate on one side).
T3a: The tumor has grown through the prostate capsule either on one side or on both sides of the prostate or has spread to the neck of the bladder.
T3b: The tumor has invaded the seminal vesicle(s), the tube(s) that carry semen.
T4: The tumor is fixed, or it is invading nearby structures besides the seminal vesicles, such as the external sphincter (part of the muscle layer that helps to control urination), the rectum, levator muscles, and/or the pelvic wall.
NODES
NX: The regional lymph nodes cannot be evaluated.
N0: The cancer has not spread to the regional lymph nodes.
N1: The cancer has spread to the regional lymph node(s).
DISTANT METASTASIS
MX: Distant metastasis cannot be evaluated.
M0: The disease has not metastasized.
M1: There is distant metastasis.
M1a: The cancer has invaded nonregional, or distant, lymph node(s).
M1b: The cancer has invaded bone(s) in the body.
M1c: The cancer has spread to another part of the body, with or without spread to the bone.
PROGNOSTIC FACTORS
PSA-GLEASON SCORE-STAGE
GLEASON SCORE
Gleason X: The Gleason score cannot be determined.
Gleason 6 or lower: The cells are well-differentiated.
Gleason 7: The cells are moderately differentiated.
Gleason 8, 9, or 10: The cells are poorly differentiated or undifferentiated .
STAGE GROUPING
Stage | T | N | M |
I | T1a, T1b, or T1c | N0 | M0 |
| T2a | N0 | M0 |
| Any T1 or T2a | N0 | M0 |
IIA | T1a, T1b, or T1c | N0 | M0 |
| T1a, T1b, or T1c | N0 | M0 |
| T2a | N0 | M0 |
| T2b | N0 | M0 |
| T2b | N0 | M0 |
IIB | T2c | N0 | M0 |
| Any T1 or T2 | N0 | M0 |
| Any T1 or T2 | N0 | M0 |
III | T3a or T3b | N0 | M0 |
IV | T4 | N0 | M0 |
| Any T | N1 | M0 |
| Any T | Any N | M1 |
Less than a month after the US Food and Drug Administration announced it was revoking bevacizumab's indication for metastatic breast cancer, citing myriad serious toxicities, more bad news for the embattled drug has emerged.
A study led by Toni K. Choueiri, MD, from the Dana-Farber Cancer Institute in Boston, Massachusetts, reports that advanced breast cancer patients treated with bevacizumab are at increased risk for congestive heart failure (CHF).
The study was published online January 4 in the Journal of Clinical Oncology. Dr. Choueiri and colleagues report a nearly 5-fold increase in the risk for CHF in bevacizumab-treated patients, compared with control subjects.
However, an accompanying editorial is critical of the paper, and urges "extreme caution" in interpreting these results.
Meta-Analysis of 5 Trials
To collect their data, Dr. Choueiri and colleagues conducted a PubMed search of articles published from 1966 to March 2010, and abstracts presented at the American Society of Clinical Oncology and San Antonio Breast Cancer Symposium annual meetings. They eventually selected 5 trials, comprising 3784 patients with metastatic breast cancer, for their final analysis.
The trials were E2100, AVADO, RIBBON-1, RIBBON-2, and a randomized phase 3 trial comparing capecitabine with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer (J Clin Oncol. 2005;23:792-799).
All these trials excluded patients with uncontrolled hypertension, clinically significant CHF, cerebrovascular disease or peripheral vascular disease, and unstable angina or a recent history of myocardial infarction. They included patients previously treated with anthracycline, and 1 trial in which patients were treated with concomitant anthracycline.
In 2 of the trials, patients had HER2-positive disease and had received previous treatment with trastuzumab.
The analysis showed close to a 5-fold increase in the risk for CHF in bevacizumab-treated patients, compared with control subjects.
Of the 2366 patients who received bevacizumab, 36 had high-grade CHF, for an overall incidence rate of 1.6% (95% confidence interval [CI], 1.0% to 2.6%). Among the 1418 control or placebo patients, 4 had CHF events, for an incidence rate of 0.4% (95% CI, 0.2% to 1.0%).
"To our knowledge, this is the first large report to show a significant increase in the risk of CHF in bevacizumab-treated patients with metastatic breast cancer," the authors write. "Patients with metastatic breast cancer may be at an especially increased risk of CHF because of prior concomitant exposure to other cardiotoxic medications in the adjuvant or metastatic settings."
Editorial Critical of Study
However, an accompanying editorial is somewhat critical of the paper, saying it has several limitations, and urging "extreme caution" in interpreting its results.
One of the editorialists, Sandra M. Swain, MD, medical director of the Washington Cancer Institute at Washington Hospital Center in DC, explained to Medscape Medical News in an interview that the editorial is critical "because the paper is just an analysis of 5 trials. It's not unique research; they're just getting data from papers that have been either published or only presented. Performing a meta-analysis with retrospectively collected heart failure data adds little to our current body of evidence."
A big limitation is previous anthracycline use among the patients. In the meta-analysis, the rate of anthracycline exposure among patients in the trials ranged from 30% to 100%.
Patients with previous anthracyclines already have a damaged heart, so it is possible that the bevacizumab could add to that. Or, it could just be related to the anthracyclines, period, and not at all related to the bevacizumab," Dr. Swain said.
Moreover, large randomized trials of bevacizumab in metastatic colorectal cancer, lung cancer, and renal cell cancer have not reported any cases of heart failure, Dr. Swain pointed out.
The lack of information about individual patients is another important limitation, she said.
"I personally don't agree with writing these kinds of papers, because — as even [the authors point] out — you're not looking at the individual patient. There was no information about the underlying risk factors that predispose to heart failure in individual patients. They didn't put in anything about cumulative [doxorubicin] dose for each patient, radiation, heart disease history, diabetes, or any of the other things that could contribute to heart failure. None of those things were evaluated, or if they were evaluated, they weren't presented."
Although the study has flaws, there are still ways that bevacizumab could be cardiotoxic, Dr. Swain said.
"Vascular endothelial growth factor is important for blood vessels, so you decrease your perfusion and decrease your ability to repair any kind of injury. If, for example, you have gotten a drug like doxorubicin that affects the heart, and then get bevacizumab afterward, you may have a limited ability to repair any kind of injury and you could develop heart failure. So there certainly are a lot of preclinical and physiologic reasons why you could have heart failure," she said.
The other adverse effect with bevacizumab that has been very clearly demonstrated and that could lead to heart failure is its effect on blood pressure. "Bevacizumab does confer a significant risk of hypertension, and there is no controversy about that. That is very clear, and the hypertension could contribute to heart failure," Dr. Swain said.
Awaiting Adjuvant Trial Results
The final word on bevacizumab's role in heart failure in advanced breast cancer will come when data from adjuvant trials are analyzed, Dr. Swain suggested.
The adjuvant trials include E5103, which was actually stopped briefly in 2009 because of fears of heart failure, but was started again, she said. They also include BEST, and BEATRICE. Together, these 3 trials should provide answers to this question, she reported.
"These trials will really give us the data because those patients are evaluated prospectively with different heart imaging. We should really wait for those trials before we pass sentence on bevacizumab with regard to heart failure. There are certainly reasons why it can occur, and it obviously did occur in some patients. The question is: Is it related to the bevacizumab or is it the anthracycline, or is it the combination of both these things, or is it because the patients had left-sided radiation? There are a lot of questions."
Dr. Choueiri reports financial relationships with Bayer/Onyx Pharmaceuticals, Novartis, GlaxoSmithKline, Genentech, Eisai, and Aveo. Dr. Swain reports that she was on an advisory board for Genentech and Roche and is the principal investigator of a National Surgical Adjuvant Breast and Bowel Project trial sponsored by Roche, but was not compensated in either instance.
