There was indeed a significant advantage to the chemotherapy and radiation therapy arm in that progression free survival was significantly longer and overall survival 88% versus 77% were significantly better in the patient’s treated with concurrent radiation and chemotherapy.

I want to go on and talk a little bit about a difficult treatment category where the exact treatment remains to be determined. This graph shows you how with increasing tumor size, whether or not lymph nodes are present that are positive, like in the upper curve or negative, one can see that the recurrence rate constantly goes up either with positive pelvic lymph nodes, negative pelvic lymph nodes and function of the size of the tumor. This is in patient’s who had radical hysterectomy and pelvic lymphadenectomy for treatment. The same is true for patient’s with stage IB carcinoma of the cervix who have been treated with radiation therapy. Here, you can see the pelvic failure rate, the distant failure rate, the disease free survival and the overall survival and function of tumor size, and with increasing tumor size, you will see an increase in pelvic failure rates and increase in the distant failure rate, the decrease and disease free survival as well as the overall survival. So, tumor size adversely affects prognosis and outcome.

If you keep in mind what a typical dose distribution is of an intracavitary implant that is used for the treatment of carcinoma of the cervix, it has this pear shaped distribution, the white here represents the tumor, this would be a barrel-shaped lesion of the cervix, a bulky lesion of the cervix, you can see here that a substantial amount of the tumor will actually be outside this radiation field which may contribute to local failure. Not surprisingly a variety of treatment approaches have been suggested for this suboptimal treatment situation of bulky or barrel-shaped tumors of the cervix, surgery, radiation therapy, radiation followed by an extra fascial or simple hysterectomy, radical hysterectomy and radiation therapy, adjuvant chemotherapy then followed by surgery or chemotherapy followed by radiation, radiation and chemotherapy at the same time, hypofractionation, that means the different varieties of radiation therapy. None of those have really consistently been shown to be breakthroughs or advantages in treatment, and again, the gynecologic oncology group reported recently on their experience and their treatment of patient’s with bulky, defined as more than 4 cm carcinoma of the cervix. Again, 368 patient’s were entered in a study and they were randomized as follows: Regimen one was radiation therapy to the pelvis and brachy therapy in the conventional way, and at the same time, cisplatin 40 mg per meter square weekly for six courses. The patient’s then went on to have an extra fascial hysterectomy which was at the time of the inception of this study still believed to be a potentially helpful maneuver. Regimen two, radiation therapy to the pelvis, brachy therapy and extra fascial hysterectomy.

This study shows a clear survival advantage. This is overall survival in the patient’s in the upper curve here, who got radiation therapy with concomitant chemotherapy at the same time, this is approximately a 30 to 45% improvement in survival here as opposed to patient’s who got radiation therapy with extra fascial hysterectomy, no concurrent chemotherapy. In the more advanced stages of cervical carcinoma, the treatment of choice is clearly radiation therapy and radiation therapy when we talk about it as a reminder, consists of internal beam radiation therapy and brachy therapy.