Nick M. Spirtos

Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group Study.

PURPOSE To compare whole-abdominal irradiation (WAI) and doxorubicin-cisplatin (AP) chemotherapy in women with stage III or IV endometrial carcinoma having a maximum of 2 cm of postoperative residual disease. PATIENTS AND METHODS Four hundred twenty-two patients were entered onto this trial. Of 396 assessable patients, 202 were randomly allocated to receive WAI, and 194 were allocated to receive AP. Irradiation dosage was 30 Gy in 20 fractions, with a 15-Gy boost. Chemotherapy consisted of doxorubicin 60 mg/m2 and cisplatin 50 mg/m2 every 3 weeks for seven cycles, followed by one cycle of cisplatin. RESULTS Most patient and tumor characteristics were well balanced. The median patient age was 63 years; 50% had endometrioid tumors. Median follow-up time was 74 months. The hazard ratio for progression adjusted for stage was 0.71 favoring AP (95% CI, 0.55 to 0.91; P < .01). At 60 months, 50% of patients receiving AP were predicted to be alive and disease free when adjusting for stage compared with 38% of patients receiving WAI. The stage-adjusted death hazard ratio was 0.68 (95% CI, 0.52 to 0.89; P < .01) favoring AP. Moreover, at 60 months and adjusting for stage, 55% of AP patients were predicted to be alive compared with 42% of WAI patients. Greater acute toxicity was seen with AP. Treatment probably contributed to the deaths of eight patients (4%) on the AP arm and five patients (2%) on the WAI arm. CONCLUSION Chemotherapy with AP significantly improved progression-free and overall survival compared with WAI. Nevertheless, further advances in efficacy and reduction in toxicity are clearly needed.

Relative influences of tumor volume before surgery and the cytoreductive outcome on survival for patients with advanced ovarian cancer: a prospective study

OBJECTIVE The purpose of this study was to determine the relative influences of the extent of disease present before surgery and completeness of cytoreduction on survival for patients with advanced ovarian cancer. METHODS Patients (408) with stage IIIC epithelial ovarian cancer had cytoreductive surgery before systemic platinum-based combination chemotherapy. A ranking system (0-3) was devised to prospectively quantify the extent of disease involving: (1) right upper quadrant (diaphragm/hepatic, and adjacent peritoneal surfaces), (2) left upper quadrant (omentum/gastro-colic ligament, spleen, stomach, transverse colon, splenic flexure of colon), (3) pelvis (reproductive organs, recto-sigmoid, pelvic peritoneum), (4) retroperitoneum (pelvic/aortic nodes), and (5) central abdomen (small bowel, ascending/descending colon, mesentery, anterior abdominal wall, pericolic gutters). Survival was analyzed (log rank and Cox regression) on the basis of the rankings at these anatomic regions, the sum of intraabdominal rankings, and the cytoreductive outcome. RESULTS Overall median and estimated 5-year survivals were 58.2 months and 49%. On univariate analysis, the central abdominal (P = 0.008) and left upper quadrant (P = 0.03) rankings, the sum of rankings (P = 0.01), and the cytoreductive outcome (P </= 0.0001) influenced survival (log rank). Survival was independently (stepwise Cox model) influenced by the sum of rankings (0-5, RR 1.00; 6-10, RR 1.24; 11-15, RR 1.44; P = 0.05), and completeness of cytoreduction (visibly disease-free, RR 1.00; </=1 cm residual, RR 2.32; >1 cm residual, RR 2.98; P = 0.001). CONCLUSIONS Cytoreduction to a visibly disease-free outcome has a more significant influence on survival than the extent of metastatic disease present before surgery. Operative efforts should not be abbreviated on the hypothesis that extensive disease at specific anatomic regions precludes long-term survival.

Recurrence and Survival After Random Assignment to Laparoscopy Versus Laparotomy for Comprehensive Surgical Staging of Uterine Cancer: Gynecologic Oncology Group LAP2 Study

PURPOSE The primary objective was to establish noninferiority of laparoscopy compared with laparotomy for recurrence after surgical staging of uterine cancer. PATIENTS AND METHODS Patients with clinical stages I to IIA disease were randomly allocated (two to one) to laparoscopy (n = 1,696) versus laparotomy (n = 920) for hysterectomy, salpingo-oophorectomy, pelvic cytology, and pelvic and para-aortic lymphadenectomy. The primary study end point was noninferiority of recurrence-free interval defined as no more than a 40% increase in the risk of recurrence with laparoscopy compared with laparotomy. RESULTS With a median follow-up time of 59 months for 2,181 patients still alive, there were 309 recurrences (210 laparoscopy; 99 laparotomy) and 350 deaths (229 laparoscopy; 121 laparotomy). The estimated hazard ratio for laparoscopy relative to laparotomy was 1.14 (90% lower bound, 0.92; 95% upper bound, 1.46), falling short of the protocol-specified definition of noninferiority. However, the actual recurrence rates were substantially lower than anticipated, resulting in an estimated 3-year recurrence rate of 11.4% with laparoscopy and 10.2% with laparotomy, or a difference of 1.14% (90% lower bound, -1.28; 95% upper bound, 4.0). The estimated 5-year overall survival was almost identical in both arms at 89.8%. CONCLUSION This study previously reported that laparoscopic surgical management of uterine cancer is superior for short-term safety and length-of-stay end points. The potential for increased risk of cancer recurrence with laparoscopy versus laparotomy was quantified and found to be small, providing accurate information for decision making for women with uterine cancer.

The impact of subspecialty training on the management of advanced ovarian cancer

A retrospective study was conducted to determine the influence of subspecialty training in gynecologic oncology as well as several other covariates on the feasibility, operative mortality, and survival benefits of cytoreductive surgery for 263 patients with stages IIIC and IVA epithelial ovarian cancer. Covariates most predictive of an optimal (< or = 1 cm) cytoreductive outcome were the diameter of the largest metastases before cytoreduction (< or = 10 cm vs > 10 cm, P < 0.001) and the specialty training of the physicians present at surgery (gynecologic oncologists vs other, P < 0.001). Age influenced operative mortality most (< 60 vs > or = 60, P < 0.001). Covariates found to most significantly influence survival time include the specialty training of the physicians present at surgery (gynecologic oncologists vs other, P < 0.0001), cytoreductive outcome (complete vs optimal, P = 0.001, optimal vs suboptimal, P < 0.0001), grade of tumor (grade 1 vs grades 2 and 3, P = 0.01), and pelvic disease status (frozen pelvis vs mobile primary tumor, P = 0.03). We conclude that patients with advanced epithelial ovarian cancer should undergo aggressive cytoreductive surgery by gynecologic oncologists, with the objective to remove all macroscopic disease. Subsequent treatment with platinum-based chemotherapy offers the best chance for long-term survival or cure.

Quality of life of patients with endometrial cancer undergoing laparoscopic International Federation of gynecology and obstetrics staging compared with laparotomy: A Gynecologic Oncology Group study

PURPOSE The studys objective was to compare the quality of life (QoL) of patients with endometrial cancer undergoing surgical staging via laparoscopy versus laparotomy. PATIENTS AND METHODS The first 802 eligible patients (laparoscopy, n = 535; laparotomy, n = 267) participated in the QoL study in a Gynecologic Oncology Group (GOG) randomized trial of laparoscopy versus laparotomy (GOG 2222). Patients completed QoL assessments at baseline; at 1, 3, and 6 weeks; and at 6 months postsurgery. RESULTS In an intent-to-treat analysis, laparoscopy patients reported significantly higher Functional Assessment of Cancer Therapy-General (FACT-G) scores (P = .001), better physical functioning (P = .006), better body image (BI; P < .001), less pain (P < .001) and its interference with QoL (P < .001), and an earlier resumption of normal activities (P = .003) and return to work (P = .04) over the 6-week postsurgery period, as compared with laparotomy patients. However, the differences in BI and return to work between groups were modest, and the adjusted FACT-G scores did not meet the minimally important difference (MID) between the two surgical arms over 6 weeks. By 6 months, except for better BI in laparoscopy patients (P < .001), the difference in QoL between the two surgical techniques was not statistically significant. CONCLUSION Although the FACT-G did not show a MID between the two surgical groups, and only modest differences in return to work and BI were found between the two groups, statistically significantly better QoL across many parameters in the laparoscopy arm at 6 weeks provides modest support for the QoL advantage of using laparoscopy to stage patients with early endometrial cancer.

A randomized phase III trial in advanced endometrial carcinoma of surgery and volume directed radiation followed by cisplatin and doxorubicin with or without paclitaxel: A Gynecologic Oncology Group study☆ , ☆☆

OBJECTIVES After surgical debulking and volume-directed irradiation of the pelvis/para-aortic lymph nodes, treatment was randomized to compare recurrence-free survival (RFS) and toxicity between two chemotherapy regimens for the treatment of women with advanced stage endometrial carcinoma. METHODS Treatment was randomized between 6 cycles of cisplatin [C] (50 mg/m(2)) and doxorubicin [D] (45 mg/m(2)) with or without paclitaxel [P] (160 mg/m(2)). Initially in paclitaxel treated patients and, after May 2002, all patients received granulocyte growth factor with each cycle. RESULTS Of 659 patients enrolled following surgery, 552 eligible patients were randomized to chemotherapy after irradiation. Accrual closed to Stage IV patients in June, 2003. Approximately 80% completed six cycles of chemotherapy. Three deaths resulted from bowel complications and one death was due to renal failure. Hematologic adverse events, sensory neuropathy and myalgia, were more frequent and severe in the paclitaxel arm (p<0.01) which was confirmed by Quality of Life assessments. Percentage of patients alive and recurrence-free at 36 months was 62% for CD vs. 64% for CDP. The hazard of recurrence or death relative to the CD arm stratified by stage is 0.90 (95% CI is 0.69 to 1.17, p=0.21, one-tail). However, in subgroup analysis, CDP was associated with a 50% reduction in the risk of recurrence or death among patients with gross residual disease (95% CI: 0.26 to 0.92). Stage, residual disease, histology/grade, positive para-aortic node and cytology, pelvic metastases and age were significantly associated with RFS. CONCLUSION The addition of paclitaxel to cisplatin and doxorubicin following surgery and radiation was not associated with a significant improvement in RFS but was associated with increased toxicity.

Cost and quality-of-life analyses of surgery for early endometrial cancer: Laparotomy versus laparoscopy

OBJECTIVE The purpose of this study was to determine whether the cost or quality of life associated with surgical treatment of presumed early-stage endometrial cancer differed on the basis of the surgical approach. STUDY DESIGN A retrospective analysis was performed on a consecutive series of women with presumed early-stage endometrial cancer treated at the Womens Cancer Center of Northern California. The senior author was the surgeon, cosurgeon, or assistant on all cases. The women comprise two groups with different surgical approaches. The first group of 17 women underwent exploratory laparotomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and aortic lymphadenectomy. The second group of 13 women underwent the same surgery by laparoscopy. The two groups were compared with a two-tailed Student t test. Variables analyzed included age, height, weight, Quetelet index, and predisposing medical problems. Lymph node counts were compiled. Hospital costs were broken down into four cost categories: (1) operating room, (2) hospital bed, (3) pharmacy, and (4) anesthesia. A two-tailed Student t test was also used in this analysis. Issues examined regarding quality of life included (1) average hospital stay, (2) complications, and (3) time to return to normal activity. RESULTS The patient population differed significantly (p < 0.05) with regard to weight and Quetelet index. The laparotomy group required significantly longer hospitalization than the laparoscopy group (6.3 vs 2.4 days, p < 0.001), resulting in higher overall hospital costs (

Lymphatic Mapping and Sentinel Lymph Node Biopsy in Women With Squamous Cell Carcinoma of the Vulva: A Gynecologic Oncology Group Study

19,158 vs

Incisional bowel herniations after operative laparoscopy: A series of nineteen cases and review of the literature☆

13,988, p < 0.05). Similarly, patients undergoing laparotomy took longer to return to normal activity (5.3 weeks vs 2.4 weeks, p < 0.0001). CONCLUSION Laparoscopic management of endometrial cancer may result in significant cost savings and improved quality of life as demonstrated by shortened hospital stays and an earlier return to normal activity.

Phase II trial of intraperitoneal paclitaxel in carcinoma of the ovary, tube, and peritoneum: a Gynecologic Oncology Group Study.

PURPOSE To determine the safety of sentinel lymph node biopsy as a replacement for inguinal femoral lymphadenectomy in selected women with vulvar cancer. PATIENTS AND METHODS Eligible women had squamous cell carcinoma, at least 1-mm invasion, and tumor size ≥ 2 cm and ≤ 6 cm. The primary tumor was limited to the vulva, and there were no groin lymph nodes that were clinically suggestive of cancer. All women underwent intraoperative lymphatic mapping, sentinel lymph node biopsy, and inguinal femoral lymphadenectomy. Histologic ultra staging of the sentinel lymph node was prescribed. RESULTS In all, 452 women underwent the planned procedures, and 418 had at least one sentinel lymph node identified. There were 132 node-positive women, including 11 (8.3%) with false-negative nodes. Twenty-three percent of the true-positive patients were detected by immunohistochemical analysis of the sentinel lymph node. The sensitivity was 91.7% (90% lower confidence bound, 86.7%) and the false-negative predictive value (1-negative predictive value) was 3.7% (90% upper confidence bound, 6.1%). In women with tumor less than 4 cm, the false-negative predictive value was 2.0% (90% upper confidence bound, 4.5%). CONCLUSION Sentinel lymph node biopsy is a reasonable alternative to inguinal femoral lymphadenectomy in selected women with squamous cell carcinoma of the vulva.