Is there a role for a brachytherapy vaginal cuff boost in the adjuvant management of patients with uterine-confined endometrial cancer?

Purpose/Objective: Many patients who have uterine-confined endometrial cancer with prognostic factors predictive of recurrence are treated with adjuvant pelvic radiation. The addition of a brachytherapy vaginal cuff boost is controversial.Materials and Methods: Between 1983 and 1993, 270 patients received adjuvant postoperative pelvic irradiation following hysterectomy for Stage I or II endometrial cancer. Group A includes 173 patients who received external beam irradiation alone (EBRT), while group B includes 97 patients who received EBRT with a vaginal brachytherapy application. The median dose of EBRT was 45 Gy. Vaginal brachytherapy consisted of a low dose rate ovoid or cylinder in 41 patients, a high dose rate cylinder in 54 patients, and a radioactive gold seed implant in two patients. The median follow-up time was 64 months. The two groups were compared in terms of age, histologic grade, favorable versus unfavorable histology, capillary space invasion, depth of myometrial invasion, and pathologic stage.Results: Chi-square analysis revealed that the only difference between the two groups was the presence of more Stage II patients in group B (38% versus 14%). No difference was detected for 5 year pelvic control and disease-free survival rates between groups A and B.Conclusion: There is no suggestion that the addition of a vaginal cuff brachytherapy boost to pelvic radiation is beneficial for pelvic control or disease-free survival for patients with Stage I or II endometrial cancer. Prospective randomized trials designed to study external irradiation alone versus external beam treatment plus vaginal brachytherapy are unlikely to show a positive result. Because EBRT provides excellent pelvic control, protocol development for uterine-confined corpus cancer should focus on identifying patients at risk for recurrence as well as other means of augmenting EBRT (e.g. addition of chemotherapy) in order to improve disease free survival in those subgroups.     

Is sex associated with the outcome of patients treated with radiation for nonsmall cell lung cancer?

BACKGROUND:

Lung cancer is the leading cause of cancer death for both men and women, but the disease course differs between the sexes. To the authors' knowledge, sex‐based differences in outcomes among the population of nonsmall cell lung cancer (NSCLC) patients receiving radiation have not been well defined.

METHODS:

Data for 831 patients (319 women and 512 men) with stage I to III NSCLC and treated with ≥45 Gray of radiation between March 1985 and November 2003 were retrospectively analyzed (grading determined according to the 1997 American Joint Committee on Cancer grading system).

RESULTS:

Women were more likely to have earlier stage disease, to have smoked <50 pack‐years, and to have adenocarcinoma or large‐cell carcinoma (all P ≤ .001). For each stage, treatment did not differ between women and men. Five‐year survival rates were significantly better for women than for men: overall survival (OS), 28.6% versus 16.1% (P < .001); disease‐free survival, 31.2% versus 20.1% (P = .02); and distant metastasis–free survival, 48.8% versus 37.6% (P < .02). Among patients with medically inoperable stage I NSCLC, women had improved 5‐year OS compared with men (30.0% vs 13.1%; P = .004). On multivariate analysis, male sex, weight loss, age ≥65 years, and stage III disease were found to be associated with poorer OS (all P < 0.02).

CONCLUSIONS:

Although women are more likely to have earlier stage disease, among patients with medically inoperable stage I NSCLC, women still have a better OS. Along with known prognostic factors, including age, weight loss, and stage, sex remained significant on multivariate analysis of OS, suggesting that sex is a determinant of outcome in NSCLC patients receiving radiation. Cancer 2009. © 2009 American Cancer Society.     

Will focal therapy become a standard of care for men with localized prostate cancer?

The current treatment choice for men with localized prostate cancer lies between active surveillance and radical therapy. The difference between these two extremes of care is 5% in terms of cancer-related absolute mortality at 8 years. It is generally accepted that this small difference will decrease for men diagnosed in the prostate-specific-antigen era. Radical therapy is associated with considerable adverse effects (e.g. incontinence, impotence, rectal problems) because it treats the whole gland, and damages surrounding structures in up to half of men. Men are being diagnosed at a younger age with lower-risk disease, and many have unifocal or unilateral disease. We propose a new concept whereby only the tumor focus and a margin of normal tissue are treated. This paradigm might decrease adverse effects whilst, at the same time, retaining effective cancer control. The arguments for and against active surveillance and radical therapy are reviewed in this article, with focal therapy presented as a means for bridging these two approaches.     

Wnt signaling can substitute for estrogen to induce division of ERα-positive cells in a mouse mammary tumor model

The interaction of estrogen with the estrogen receptor (ER, principally ERα) induces growth of human breast tumor cells. In contrast, ERα-positive cells have been described as non-dividing cells in normal breast (though estrogen stimulation of ERα cells directs the division of neighboring cells). However, there is a small sub-population of cells in normal mammary tissue that are ERα-positive, that can divide, and therefore share this property with human breast tumor cells. In order to investigate their pattern of growth regulation, we measured the fraction of dividing ERα⁺ cells during normal growth and compared that to glands stimulated by oncogenic Wnt effectors. First, we found there was no difference between the rate of division of ERα⁺ cells and ERα⁻ cells, whether the population was responding to estrogen or Wnt mitogens. The proportion of dividing ERα⁺ mammary epithelial cells was increased (10×) in response to pregnancy, and similar increases were observed in response to ectopic Wnt signaling. We propose that Wnt signaling can substitute for estrogen to drive total population growth (that includes ERα⁺ cells). Although the E-ERα-derived mitogenic response is situated in a minority of the luminal cells, and the Wnt-LRP5/6-derived mitogenic response is situated in a minority of basal cells, overall, the growth response of the mammary epithelial population is remarkably similar.     

Is there a role for urokinase-type plasminogen activator inhibitors as maintenance therapy in patients with ovarian cancer?

There is abundant evidence that the urokinase-type plasminogen activator (uPA), its inhibitors PAI-1 and PAI-2 (plasminogen activator inhibitor type-1 and type-2) and its cells surface receptor (uPA-R, CD87) play a fundamental role in tumor invasion and metastasis and are of significant prognostic significance for many tumor types. We performed a systematic Med-line search on uPA, PAI, uPA-R and (epithelial) ovarian cancer (EOC). The majority of malignant EOC specimens show moderate to strong immunostating of tumor and stromal cells. Overexpression of u-PA and PAI-1 can be found in more the 75% of primary ovarian carcinomas, in most metastatic EOC samples and all examined epithelial ovarian cancer cell lines. uPA overexpression in primary specimens was significantly associated with tumor stage, grade, residual disease status after cytoreductive surgery, and poor clinical outcome. This may be explained by increased chemoresistance, a lower resectability and more aggressive tumor biology and tumor dissemination in patients with high uPA and PAI-1. Several therapeutical approaches aimed at inhibiting the uPA/uPAR functions have shown to possess anti-tumor effects in vitro and in animal models. When treating a patient with advanced ovarian cancer it may to be assumed that inhibiting the progression of established (micro) metastases may be more therapeutically relevant than trying to destroy all tumor cells which is not possible in most cases with current systemic treatment modalities. Taking into account the role of uPA and PAI in cell detachment, formation of new stroma, tumor cell reimplantation and metastasis uPA inhibition should be further investigated as maintenance treatment in patients with advanced EOC.