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BACKGROUND. The objective was to examine whether rates of disease recurrence, treatment-related adverse effects, and survival differed between obese or morbidly obese and nonobese patients. METHODS. Data from patients who participated in a randomized trial of surgery with or without adjuvant radiation therapy were retrospectively reviewed. RESULTS. Body mass index (BMI) data were available for 380 patients, of whom 24% were overweight (BMI, 25–29.9), 41% were obese (BMI, 30–39.9), and 12% were morbidly obese (BMI, ≥40). BMI did not significantly differ based on age, performance status, histology, tumor grade, myometrial invasion, or lymphovascular-space involvement. BMI > 30 was more common in African Americans (73%) than non-African Americans (50%). Patients with a BMI ≥ 40 compared with BMI < 30 (hazards ratio [HR], 0.42; 95% confidence interval [CI], 0.09–1.84; P = .246) did not have lower recurrence rates. Compared with BMI < 30, there was no significant difference in survival in patients with BMI 30–39.9 (HR, 1.48; 95% CI, 0.82–2.70; P = .196); however, there was evidence for decreased survival in patients with BMI ≥ 40 (HR, 2.77; 95% CI, 1.21–6.36; P = .016). Unadjusted and adjusted BMI hazards ratios for African Americans versus non-African Americans in the current study differed, thus suggesting a confounding effect of BMI on race. Eight (67%) of 12 deaths among 45 morbidly obese patients were from noncancerous causes. For patients who received adjuvant radiation therapy, increased BMI was significantly associated with less gastrointestinal (R, −0.22; P = .003) and more cutaneous (R, 0.17; P = .019) toxicities. RESULTS. In the current study, obesity was associated with higher mortality from causes other than endometrial cancer but not disease recurrence. Increased BMI was also associated with more cutaneous and less gastrointestinal toxicity in patients who received adjuvant radiation therapy. Future recommendations include lifestyle intervention trials to improve survival in obese endometrial cancer patients. Cancer 2006. © 2006 American Cancer Society.

Objective To evaluate, in a randomized clinical trial, the role of adjuvant hysterectomy after standardized radiation in improving progression-free survival and survival for patients with “bulky” stage IB cervical cancer. Methods A total of 256 eligible patients with exophytic or “barrel” shaped tumors measuring ≥4 cm were randomized to either external and intracavitary irradiation (RT, N = 124) or attenuated irradiation followed by extrafascial hysterectomy (RT + HYST, N = 132). Twenty-five percent of patients had tumors with a maximum diameter of ≥7 cm. Results Tumor size was the most pronounced prognostic factor followed by performance status 2 and age at diagnosis. Hysterectomy did not increase the frequency of reported grade 3 and 4 adverse effects (both groups, 10%). The majority of these adverse effects were from the gastrointestinal or genitourinary tracts exclusively. There was a lower cumulative incidence of local relapse in the RT + HYST group (at 5 years, 27% vs. 14%). There were no statistical differences in outcomes between regimens except for the adjusted comparison of progression-free survival, although all indicated a lower risk in the adjuvant hysterectomy regimen (unadjusted relative risk [URR] of progression, 0.77, P = 0.07; URR of death, P = 0.26, both one tail). Conclusion Overall, there was no clinically important benefit with the use of extrafascial hysterectomy. However, there is good evidence to suggest that patients with 4-, 5-, and 6-cm tumors may have benefitted from extrafascial hysterectomy (URR of progression; 0.58; URR of death, 0.60).

Bulky stage IB cervical cancers have a poorer prognosis than smaller stage I cervical cancers. For the Gynecologic Oncology Group, we conducted a trial to determine whether weekly infusions of cisplatin during radiotherapy improve progression-free and overall survival among patients with bulky stage IB cervical cancer.Women with bulky stage IB cervical cancers (tumor,or =4 cm in diameter) were randomly assigned to receive radiotherapy alone or in combination with cisplatin (40 mg per square meter of body-surface area once a week for up to six doses; maximal weekly dose, 70 mg), followed in all patients by adjuvant hysterectomy. Women with evidence of lymphadenopathy on computed tomographic scanning or lymphangiography were ineligible unless histologic analysis showed that there was no lymph-node involvement. The cumulative dose of external pelvic and intracavitary radiation was 75 Gy to point A (cervical parametrium) and 55 Gy to point B (pelvic wall). Cisplatin was given during external radiotherapy, and adjuvant hysterectomy was performed three to six weeks later.The relative risks of progression of disease and death among the 183 women assigned to receive radiotherapy and chemotherapy with cisplatin, as compared with the 186 women assigned to receive radiotherapy alone, were 0.51 (95 percent confidence interval, 0.34 to 0.75) and 0.54 (95 percent confidence interval, 0.34 to 0.86), respectively. The rates of both progression-free survival (P0.001) and overall survival (P=0.008) were significantly higher in the combined-therapy group at four years. In the combined-therapy group there were higher frequencies of transient grade 3 (moderate) and grade 4 (severe) adverse hematologic effects (21 percent, vs. 2 percent in the radiotherapy group) and adverse gastrointestinal effects (14 percent vs. 5 percent).Adding weekly infusions of cisplatin to pelvic radiotherapy followed by hysterectomy significantly reduced the risk of disease recurrence and death in women with bulky stage IB cervical cancers.

Between June 1987 and July 1995, 448 women with endometrial cancer were enrolled in a prospective, randomized trial comparing the use of postoperative radiation versus no postoperative treatment. Participants had stage IB, IC, II, or IIB endometrial adenocarcinoma with an intermediate risk of recurrence (that is, tumor with any degree of myometrial invasion, adenocarcinoma of any grade, and no evidence of lymph node involvement). In addition, an analysis was performed of 2 subgroups. High-risk patients had all of these risk factors: moderate to poorly differentiated tumor, presence of lymphvascular invasion, and myometrial invasion to the outer third; they were 50 years of age or older with 2 of the 3 risk factors; or they were 70 years of age or older and had one additional risk factor. Women who did not qualify for the high-risk subgroup were considered in the low-risk subgroup. Three hundred ninety-two participants met all eligibility requirements for inclusion in the analysis. Two hundred two women were randomized to the whole pelvic radiation group, and 190 received no additional postoperative treatment. Otherwise, both groups had similar clinical and demographic characteristics. In the radiation therapy (RT) group, 13 patients refused postoperative treatment and 5 received less than the prescribed dose. In the no-treatment group, 2 patients received fall-dose postoperative RT. Twenty-four participants were lost to follow up within a median of 50 months. Overall median follow up was 68 months. Forty-four patients, 31 in the unirradiated group and 13 in the radiation group, developed disease recurrence. After a median follow up of 80 months, 15 of the women who recurred were alive with disease. In all, 66 women in the study died, 32 from disease or treatment-related causes. Women who received postoperative radiation therapy were less likely to have a recurrence of disease than those who had no additional treatment Among the 202 patients who had no postoperative treatment, 13 recurred in the vagina, 4 in the pelvis, 1 in the vagina and pelvis, and 13 had distant recurrences. In the RT group, 2 women, both of whom refused treatment with radiation, had a recurrence in the vagina. One other patient recurred in the vagina and pelvis, and 10 had distant recurrences. Patients who were treated with postoperative radiation therapy had a 58% lower risk of ever having a recurrence of disease than women who did not. The overall risk of recurrence in the first 24 months after treatment was 3% (90% confidence interval [CI], 0.02-0.06) for women who received RT and 12% (90% CI, 0.09-0.17) for women who had no additional treatment. The estimated cumulative risk of recurring in the vagina or pelvis within the first 24 months was 1.6% (90% CI, 0.6-3.9) for those in the RT group compared with 7.4% (90% CI, 4.9-11.0) for the no additional treatment group. In the 132 women who were in the high-risk subgroup, 28 (28 of 44; 64%) had a recurrence of disease and 22 died from disease (22 of 32; 67%). The estimated risk of recurrence for high-risk women was 0.46 (90% CI, 0.19-1.11) compared with 0.42 (90% CI, 0.21-0.83) for low-risk women. There were 2 deaths from intestinal injury associated with radiation treatrnent. Overall, there were 6 instances of bowel obstruction in the RT group and 1 in the no additional treatment group.

Between 1977 and 1985, the Gynecologic Oncology Group (GOG) conducted three clinical trials in locally advanced carcinoma of the cervix, clinical Stages I to IVA as classified by the International Federation of Gynecology and Obstetrics (FIGO). All 626 patients had primary carcinoma of the cervix and underwent operative assessment of the para-aortic (PA) lymph nodes. Patients received standardized external radiation therapy to the pelvis or to the pelvis and PA lymph nodes followed by one or two brachytherapy applications. To date, no statistically significant differences in progression-free interval (PFI) or survival time have been identified between the randomization treatment arms on any of these studies. Basic similarities among these studies led us to pool these data to identify patient characterisitcs and tumor characteristics associated with an increased risk of treatment failure. Multi-variate analysis showed patient age, performance status (PS), PA lymph node status, tumor size, and pelvic node status to be significantly associated with PFI. When modeling for survival, all these factors and clinical stage and bilateral extension were significant.

The objective of the study was to confirm that concurrent cisplatin (CT) with radiation therapy (RT) is associated with improved long-term progression-free survival (PFS) and overall survival (OS), compared with RT alone in stage IB bulky carcinoma of the cervix, when both groups' therapy is followed by hysterectomy.Three hundred seventy-four patients entered this trial. There were 369 evaluable patients; 186 were randomly allocated to receive RT alone and 183 to receive CT plus RT. Radiation dosage was 45 Gray (Gy) in 20 fractions followed by low dose-rate intracavitary application(s) of 30 Gy to point A. Chemotherapy consisted of intravenous cisplatin 40 mg/m2 every week for up to 6 weekly cycles. Total extrafascial hysterectomy followed the completion of RT by 6-8 weeks.Preliminary results have been published, at which time there were 292 censored observations, and median duration of follow-up was only 36 months. Patient and tumor characteristics were well balanced between the regimens. The median patient age was 41.5 years; 81% had squamous tumors; 59% were white. Median follow-up is now 101 months. The relative risk for progression was 0.61 favoring CT plus RT (95% confidence interval [CI] 0.43 to 0.85, P.004). At 72 months, 71% of patients receiving CT plus RT were predicted to be alive and disease free when adjusting for age and tumor size, compared with 60% of those receiving RT alone. The adjusted death hazard ratio was 0.63 (95% CI 0.43 to 0.91, P.015) favoring CT plus RT. At 72 months, 78% of CT plus RT patients were predicted to be alive, compared with 64% of RT patients. An increased rate of early hematologic and gastrointestinal toxicity was seen with CT plus RT. There was no detectable difference in the frequency of late adverse events.Concurrent weekly cisplatin with RT significantly improves long-term PFS and OS when compared with RT alone. Serious late effects were not increased. The inclusion of hysterectomy has been discontinued on the basis of another trial. Pending further trials, weekly cisplatin with radiation is the standard against which other regimens should be compared.

Background . Despite their low risk for recurrence, many women with endometrial adenocarcinoma receive postoperative radiation therapy (RT). This study was developed to determine if adjunctive external beam irradiation lowers the risk of recurrence and death in women with endometrial cancer International Federation of Gynaecology and Obstetrics (FIGO) stages IB, IC, and II (occult disease). Methods . Four hundred forty-eight consenting patients with "intermediate risk" endometrial adenocarcinoma were randomized after surgery to either no additional therapy (NAT) or whole pelvic radiation therapy (RT). They were followed to determine toxicity, date and location of recurrence, and overall survival. A high intermediate risk (HIR) subgroup of patients was defined as those with (1) moderate to poorly differentiated tumor, presence of lymphovascular invasion, and outer third myometrial invasion; (2) age 50 or greater with any two risk factors listed above; or (3) age of at least 70 with any risk factor listed above. All other eligible participants were considered to be in a low intermediate risk (LIR) subgroup. Results . Three hundred ninety-two women met all eligibility requirements (202 NAT, 190 RT). Median follow-up was 69 months. In the entire study population, there were 44 recurrences and 66 deaths (32 disease or treatment-related deaths), and the estimated 2-year cumulative incidence of recurrence (CIR) was 12% in the NAT arm and 3% in the RT arm (relative hazard (RH): 0.42; P = 0.007). The treatment difference was particularly evident among the HIR subgroup (2-year CIR in NAT versus RT: 26% versus 6%; RH=0.42). Overall, radiation had a substantial impact on pelvic and vaginal recurrences (18 in NAT and 3 in RT). The estimated 4-year survival was 86% in the NAT arm and 92% for the RT arm, not significantly different (RH: 0.86; P = 0.557). Conclusions . Adjunctive RT in early stage intermediate risk endometrial carcinoma decreases the risk of recurrence, but should be limited to patients whose risk factors fit a high intermediate risk definition.

Several large, prospectively randomized clinical trials run by multi-institutional cooperative groups have established that the best treatment for advanced cancer of the cervix is primary radiotherapy with concurrent, cisplatin-based chemotherapy. In fact, patients with earlier stage cervix cancer with poor prognostic indicators (large, bulky tumors, positive pelvic lymph nodes, or unexpected parametrial disease at the time of surgery) also show a survival benefit with this approach. Adequate radiation dosing (both external beam and intracavitary) is essential. The additional benefit of periaortic lymph node irradiation is debated, but generally accepted, for patients with locally advanced disease or pelvic lymph node involvement.

We examined whether the cell proliferation index by MIB-1, HER-2/neu gene amplification, Gleason grade, and pretreatment level of serum prostate specific antigen (PSA) correlated with postradiation recurrence (PRR) in patients with prostatic adenocarcinoma. Formalin-fixed, paraffin-embedded tissue sections from 42 pretreated cases of prostatic adenocarcinoma (38 needle biopsy and 4 transurethral resection specimens) were immunostained for MIB-1 (MMI, Ventana Medical Systems, Tucson, Ariz). HER-2/neu gene amplification was analyzed by fluorescence in situ hybridization using the Oncor unique sequence probe (Oncor, Gaithersburg, Md). The cell proliferation index by MIB-1 was determined by labeling index; levels of HER-2/neu were analyzed semiquantitatively. Twenty-three of 42 patients (55%) were considered to have PRR on the basis of consecutive elevations of serum levels of PSA to greater than 1.5 ng/mL after completion of treatment (mean follow-up time, 33.4 months). The cell proliferation index correlated with PRR on both univariate and multivariate analyses. Of the 23 tumors that showed PRR, 18 (78%) revealed a high cell proliferation index, compared with 6 of 19 cases (32%) that showed no PRR. Twelve of 23 cases of prostatic adenocarcinoma (52%) in the recurrent group showed HER-2/neu gene amplification, compared with 5 of 19 (26%) in the nonrecurrent group; these findings reached near significance on univariate analysis. Pretreatment levels of serum PSA also reached significance on multivariate analysis. In this preliminary study, the cell proliferation index by MIB-1 reached independent significance in predicting PRR in patients with prostatic adenocarcinoma, whereas HER-2/neu amplification by fluorescence in situ hybridization reached near significance.

Objective. The aim of this study was to investigate local regional control, survival, and morbidity in patients with FIGO IIB and IIIB squamous cell carcinoma of the cervix treated with primary extended field (prophylactic paraaoratic radiation) radiation and weekly cisplatin. Methods. Sixty-seven patients (44 IIB and 23 IIIB) with carcinoma of the cervix received cisplatin at 1 mg/kg (up to 60 mg) weekly and extended field radiation therapy including the paraaortic nodes and brachytherapy. Results. After the scheduled therapy 94.1% of the patients were complete responders. Seventy-five percent are alive without evidence of disease with a mean follow-up of 47.5 months. Conclusion. This study confirms the ability to give concomitant weekly cisplatin and prophylactic paraaortic radiation with minimal morbidity. The encouraging Kaplan–Meier survival of 75% and only eight pelvic failures warrants further investigation.

Objective. To evaluate a regimen of radiation and chemotherapy as an alternative for those patients in whom the location and extent of advanced vulvar carcinoma make pelvic exenteration the only surgical option. Methods. Between December 1988 and March 1995, 14 patients with primary squamous carcinoma of the vulva who were not candidates for standard radical vulvectomy were treated with radiation therapy in combination with cisplatin and 5-fluorouracil (5-FU) chemotherapy at the Albany Medical Center. Patients ranged in age from 40 to 90 years, mean 68. Tumors were stage III in 9 patients and stage IV in 5 patients. Treatment included two cycles of chemotherapy with cisplatin (50 mg/m 2 ) and 5-FU (1000 mg/m 2 /24 × 96 hr) in addition to radiation therapy. Total radiation doses to the vulva and groins ranged from 50 to 65 Gray (Gy), with pelvic doses of 45 to 50 Gy. Surgical excision of the primary site was not performed in patients who had complete clinical response. Results. Acute complications included desquamation requiring treatment interruptions in 5 patients and deep venous thrombosis in 1 patient. Delayed complications were limited to small bowel obstruction and colonic stricture in one patient. There was a 92% response rate with complete responses in 9 patients (64%). Among patients with complete clinical response, there has been only one recurrence with follow-up of 7–81 months, mean 36.5. All patients with partial responses died, with survival of 8–25 months, mean 15.7. Conclusions. This combination of chemoradiation was found to be effective therapy for locally advanced vulvar carcinoma, with acceptable morbidity even in an elderly population. Surgical excision of the primary site is not necessary in patients with complete response.

5530 Background: Conflicting results have been reported for adeno- and adenosquamous carcinomas the cervix with respect to their response to therapy and prognosis. Adeno- and adenosquamous carcinoma comprise the majority of non-squamous carcinomas of the cervix enrolled in GOG trials of chemoradiation. Methods: Adeno- and adenosquamous cervical carcinomas were retrospectively studied and compared to squamous cell carcinomas in GOG trials of chemoradiation. Results: Among 1672 patients enrolled in clinical trials of chemoradiation, 182 adeno- and adenosquamous carcinomas were identified (10.8%). A higher percentage of adeno- and adenosquamous carcinomas were stage IB (27% versus 20%) and fewer were stage IIIB (21.4% versus 28.6%). The mean tumor size was larger for squamous than adeno- and adenosquamous carcinomas, but adeno- and adenosquamous carcinomas were more often poorly differentiated (46.2% versus 26.8%). Among patients that received cis-platinum during radiation therapy, 843 with squamous cell carcinoma were compared to 112 with adeno- or adenosquamous carcinoma for overall survival, with no significant difference in risk of death (p=0.472). However, among patients that did not receive cis-platinum, 647 with squamous cell carcinoma and 70 with adeno- or adenosquamous carcinoma, there was a slightly higher risk of death for the adeno- or adenosquamous group (p=0.049). Adverse effects to treatment were similar across histologies. Conclusions: Patients with adeno- and adenosquamous carcinomas of the cervix have worse overall survival when treated with radiation alone, but have progression-free and overall survival similar to patients with squamous cell carcinomas of the cervix when treated with cis-platinum based chemoradiation.

A 41-year-old black woman had a radical hysterectomy and bilateral pelvic node dissection for a stage IB squamous cell carcinoma. No poor-risk factors were noted on histologic study. Five months later, she had a 7 cm recurrence attached to the vaginal cuff and associated with left hydronephrosis. Periaortic adenopathy was noted on a computed tomography (CT) scan. Within 3 weeks, the pelvic mass had enlarged.

A Phase I/II trial of weekly cisplatin and extended field radiation therapy for cervical carcinoma and paraaortic metastases was initiated. A total of 13 patients have entered this trial since 1985. The objective of the study was to determine the efficacy and toxicity of extended field radiation therapy and cisplatin as a radiation sensitizer in this high-risk group of patients. The addition of paraaortic nodal radiation was derived from our earlier trial using cisplatin and pelvic radiation therapy followed by combination chemotherapy (cisplatin, adriamycin and cytoxan). Of the 13 patients entered, 8 are alive without evidence of disease and 5 have recurred, all exclusively outside the treatment fields. Three of the five had positive scalene node biopsies prior to the initiation of therapy. Four patients have died from distant metastases, one is alive with lung and bone metastases, and there have been no recurrences in the pelvis or paraaortic treated areas. The encouraging results of complete local and pelvic control of tumor and acceptable toxicity warrants continuation of this trial.

The incidence of para-aortic node metastasis in cancer of the cervix ranges from 5% to 50% in clinical Stages I-IV. Extended field irradiation is being administered more frequently because of the high incidence of extrapelvic disease. The cancer of the cervix material at Walter Reed General Hospital has been analyzed as to site and time of failure to determine who might have benefited from extended field irradiation. Of patients who fail, the majority will have uncontrolled pelvic disease regardless of other involvement. Diagnostic procedures including staging laparotomy are unable to predict pelvic failure or the presence of occult distant disease in lung and bone. The maximum number of patients who could benefit from para-aortic irradiation is less than 3% of a total series. It is concluded that the salvage of patients with para-aortic metastasis will be small, but for those few long-term survivors, the benefit will be great.

The effect of an informational intervention that provided objective descriptions, in concrete terms, of the usual experiences during the various phases of radiation therapy was tested in a random clinical trial. The patients had Stage A, B, or C prostatic cancer. Forty-two control patients received the information routinely provided to all patients in the treatment setting. Forty-two experimental patients received, in addition, four informational messages during the course of radiation therapy. The first message described the experience of treatment planning; the second described the experience of receiving a radiation treatment; the third described side effects that usually occur, their onset, their characteristics, and activities to lessen their impact; and the fourth described the usual experiences during the months following radiation treatments. The experimental group of patients, compared with those in the control group, reported significantly less disruption in usual activities during and following radiation therapy. The amount of emotional disturbance was low and did not differ by study group. The results of this study, with respect to the interventions' effect on radiation therapy patients' quality of life, were consistent with prior research in other health care situations.

Between June 1981 and December 1985, 296 evaluable patients with carcinoma of the cervix (stages IIB, III, or IVA) were randomized to radiation therapy and either hydroxyurea (139 patients) or misonidazole (157 patients). All patients had undergone clinical, radiographic, and surgical staging. Patients with metastasis to periaortic nodes were ineligible for study. Patients received external radiation therapy to the pelvis and either one or two intracavitary applications. Hydroxyurea was given in a dose of 80 mg/kg each Monday and Thursday during external radiation therapy. Misonidazole was given in a dose of 1 gm/m2 in the same schedule, not to exceed 12 gm/m2. Of the evaluable patients, 60.8% had stage IIB disease and 33.8% had stage IIIB disease. Negative pelvic lymph nodes were found in 79.2% of the patients. Median age was 49 years (first and third quartiles 40 and 60, respectively). There were 51 patients who had severe and 15 patients who had life-threatening adverse effects (including two treatment-related deaths). As of February 1987 half the patients have either failed or been followed-up for at least 43 months. The group treated with hydroxyurea had a longer progression-free interval, bordering on statistical significance, than those treated with misonidazole (p = 0.08). The median progression-free interval for all patients randomized to hydroxyurea is 42.9 months and for misonidazole it is 40.4 months. The median progression-free interval for patients with stage III and IV disease who received hydroxyurea has not been reached and for the misonidazole group it was 10.1 months. There have been 120 recurrences, 51 (36.7%) in the hydroxyurea group and 69 (43.9%) in the misonidazole group; 51.7% of the recurrences have been limited to the pelvis or vagina. Failure limited to the pelvis occurred in 18.0% of patients receiving hydroxyurea and 23.6% of patients receiving misonidazole. There were 108 deaths, 47 (33.8%) in the hydroxyurea group and 61 (38.9%) in the misonidazole group; survival does not differ statistically between the two regimens at this point in follow-up (p = 0.25). Hydroxyurea has more short-term gastrointestinal and marrow toxicity, but is free of long-term neurotoxicity. Preliminary analyses indicate that there is no role for radiation therapy with misonidazole in cervical carcinoma.

Change in therapy has become the standard approach for the management of breast cancer in this multidisciplinary era. The role of radiation therapy is changing, as is the role of surgery. Radical mastectomy is no longer generally acceptable as the treatment of choice by surgeons, and routine postoperative radiation therapy is in dispute among radiation oncologists. With newer methods of detection and advances in adjuvant chemotherapy programs, a new literature is emerging and new approaches offering better survival results and better cosmesis are promised. Individualization, rather than standardization, marks the therapeutic effort in most cancer centers.

The use of 3 dose assessment systems is compared. The Manchester approach which measures a dose to Point A and Point B; the Paris approach using rads and mgh; and Ellis's NSD approach appear to have equal value in predicting probability of pelvic control and the likelihood of complication over the dose range employed at this hospital. Control increases with higher dose schemes, but complications appear to be influenced by other variables not accounted for in the 3 systems.