A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study

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.     

Pelvic bone complications following radiation therapy of gynecologic malignancies: clinical evaluation of radiation-induced pelvic insufficiency fractures

OBJECTIVE: To investigate the incidence, clinical and imaging finding of insufficiency fractures (IF) of the female pelvis following radiation therapy. METHODS: We reviewed the radiation oncology records of 158 patients with gynecologic malignancies who underwent external beam radiation therapy of the whole pelvis between April 1993 and March 2004. All patients underwent computed tomography (CT) scan every 6 months in follow-up after radiation therapy and magnetic resonance imaging (MRI) and radionuclide bone scan were added when the patients complained of a pelvic pain. RESULTS: Eighteen of 158 patients (11.4%) developed IF in the irradiated field with a median interval of 6 months (range 3-51) from the completion of external beam radiation therapy. The cumulative incidence of symptomatic IF at 5 years calculated with Kaplan-Meyer methods was 13%. Median age of the patients who developed IF was 70 years (range 48-88), and all of them were postmenopausal. IF occurred in the sacloiliac joints, upper limb of pubic bone, acetabulum, sacral body and 5th lumbar vertebra. Twelve of 18 patients had multiple lesions and 8 had symmetric longitudinal fracture lines parallel to the sacroiliac joints. Avoidance of weight bearing by bed rest and analgesics provided good pain relief in all patients, although symptoms lasted from 3 to 20 months. CONCLUSIONS: Radiation-induced pelvic IF following radiation therapy for gynecologic malignancies were frequently observed in the postmenopausal patients within 1 year after external beam radiation therapy. Symmetric fractures of the both sacroiliac joints were the characteristic pattern of pelvic IF. Knowledge of characteristic imaging pattern of IF is essential in order to rule out the bone metastasis. Therapy recommendations are conservative with analgesics.     

10-Gy single-fraction pelvic irradiation for palliation and life prolongation in patients with cancer of the cervix and corpus uteri.

OBJECTIVE: The goal of this study was to evaluate the effects of single fractions of 10 Gy pelvic irradiation for palliation and life prolongation in patients with cancer of the uterine cervix or corpus. METHODS: A retrospective analysis was performed on 37 cervical cancer and 27 corpus cancer patients treated in the period 1988-1998. All patients had a life expectancy of less than 1 year. Due to stage of disease, age (median 82 years), or comorbidity they were considered unapt for surgery or conventional radiotherapy. Eleven patients with recurrence within irradiated field or early progression received one, 51 patients received two, and 2 patients received three fractions with a 4-week interval. RESULTS: Vaginal bleeding stopped in 90% and malodorous discharge in 39% of the patients. Among 46 patients with advanced disease treated for palliation, 10 (22%) showed complete tumor responses. Median time to progression was 6 months, and median survival, 9 months. Eighteen patients with early-stage disease and serious comorbidity were treated with life prolongation and symptom prevention as intention, and showed seven complete responses. Median survival was 13 months, and half the deaths were caused by intercurrent disease. Median hospital stay was 5 days and rehabilitation was easy. Fifty-six percent of the patients experienced no acute side effects and 33% had minor gastrointestinal problems. Three patients (6%) had serious late bowel complications, one with a fatal outcome, the symptoms appearing 9-10 months posttreatment. CONCLUSION: The 10-Gy single-fraction pelvic radiation regimen is an effective means of symptom palliation and is well tolerated. Tumor responses are obtained. The risk of late bowel complications is a concern for patients with a life expectancy greater than 9 months.     

Risk factors for postoperative femoral fracture in cementless hip arthroplasty.

The objective of this study was to evaluate the incidence of and risk factors for femoral fracture in patients who underwent cementless hip arthroplasty during a 3-year period. Several predisposing factors have been reported; we tried to find another predictive indicator that could be recognized preoperatively. The records of all patients who underwent cementless hip arthroplasty from December 1993 to December 1996 were reviewed. The characteristics and clinical features (including age, gender, diagnosis, geometry of the proximal femur, and quality of bone) of the patients who had fractures were compared with those of patients who did not have fractures. During the 3-year study, 425 patients underwent a total of 454 cementless hip arthroplasties. There were 16 postoperative fractures (3.5%, 16 patients). Patients who suffered femoral fracture were significantly older than patients without fracture (65.6 +/- 10.9 yr vs 52.6 +/- 16.2 yr, p < 0.001). The fracture group had poorer preoperative bone quality compared with the nonfracture group (3.3 +/- 0.6 vs 3.8 +/- 0.7, Singh's Index of Osteoporosis, p < 0.01). The canal flare index of the proximal femur was significantly lower in the fracture group than in the nonfracture group (3.3 +/- 0.40 vs 3.8 +/- 0.7, p < 0.01). Our results indicate that old age and osteoporosis affect the likelihood of periprosthetic femoral fractures, and that a low flare index is a predictive indicator of femoral fracture. These factors should be taken into account during preoperative planning, and cemented arthroplasty should be considered for patients with these risk factors.     

Pelvic insufficiency fractures in patients with cervical and endometrial cancer treated with postoperative pelvic radiation

ObjectiveThere is an increased awareness of pelvic insufficiency fractures (PIF) as a potential morbidity of pelvic radiotherapy (RT). The purpose of this study was to determine the incidence of PIF and assess prognostic factors, including intensity-modulated RT (IMRT), in gynecologic oncology patients treated with postoperative pelvic RT.MethodsWe performed a retrospective review of all patients with endometrial or cervical carcinoma who received postoperative pelvic RT at our institution during 2000–2008. Patients who received definitive or palliative RT were excluded.ResultsA total of 222 patients were identified, of whom 11 (5%) developed PIF at a median time of 11.5 months (range, 5.5–87.3 months) from RT completion. The 5-year actuarial rate was 5.1% (95% CI 3.3–6.9). In patients with osteoporosis, the 5-year rate was 15.6% compared with 2.9% for those without (P = 0.01). Similarly, patients who were on prior hormone-replacement therapy (HRT) had a higher rate (14.8% vs 4.1%, P = 0.009). The median body-mass index (BMI) for patients who developed PIF was significantly lower than those who didn't (25.9 vs 27.2, P = 0.016). The rate of PIF was 4.9% whether patients received IMRT or conventional RT.ConclusionsThe 5-year risk of PIF for postoperative pelvic RT in cervical and endometrial cancer is 5.1%. Women with history of osteoporosis, prior HRT, or low BMI need to be counseled about the risk of PIF. The use of IMRT did not decrease PIF, but further studies are needed to determine if a dose/volume relationship exists between RT and PIF.     

Surgical treatment of unexpected invasive cervical cancer found at total hysterectomy.

OBJECTIVE: To determine the proper management of patients found to have invasive cancer of the cervix on pathologic examination of a uterus removed for benign indications. METHODS: We report 18 patients undergoing hysterectomy who were found to have cervical cancer with invasion deeper than 3 mm and/or lymph-vascular space involvement. None had gross residual tumor following simple hysterectomy. All patients underwent a second operation. Seventeen women underwent a radical parametrectomy, upper vaginectomy, and pelvic lymphadenectomy; one had pelvic and periaortic lymphadenectomy alone because of bilateral grossly positive obturator nodes. RESULTS: Median follow-up was 72 months. One of the 15 women without residual disease or nodal involvement at second operation had pelvic recurrence 66 months after therapy. Three patients with disease identified at radical surgery underwent tailored postoperative pelvic radiation, and two of these had pelvic recurrence. The overall actuarial 5-year survival for the 18 patients was 89%. Operative morbidity was comparable to that of patients undergoing primary radical hysterectomy. CONCLUSION: This study confirms that patients with unexpected invasive cervical cancer found at total hysterectomy can undergo radical re-operation with low morbidity and excellent cure rates.     

Pelvic exenterations for gynecological malignancies: twenty-year experience at Roswell Park Cancer Institute

The objective of this study is to review the experience with pelvic exenterations for gynecological malignancies at our cancer institute. Charts of 48 women who underwent a pelvic exenteration between January 1980 and December 1999 were reviewed, and several outcomes were analyzed. Majority of patients had received prior radiation therapy. The median survival was 35 months, and the disease-free survival was 32 months. Mortality from the procedure was 4.2%. Early and late postoperative complication rates were 27% and 75%, respectively. Recurrence rate was 60%. Eight patients received intraoperative radiation. Median survival in this group was 11.3 vs 35 months (P = 0.003). Univariate analysis failed to show an association between type of pelvic exenteration, type of fecal and urinary diversion, outcome, need for reoperation, and recurrence. Contemporary pelvic exenterations are associated with a low mortality and a potential for long-term survival in a subset of patients who historically have been given a poor prognosis. In patients with recurrent gynecological cancer confined centrally to the pelvis, pelvic exenteration still remains the choice of therapy as response to chemotherapy to a centrally recurrent tumor in radiated area continues to be poor. Intraoperative radiation in select few patients needs to be further studied.     

Early stage cervical cancer with negative pelvic lymph nodes: pattern of failure and complication following radical hysterectomy and adjuvant radiotherapy

PURPOSE OF INVESTIGATION: The objective was to optimize the adjuvant treatment for patients with lymph node negative cervical cancer by analyzing patterns of failure and complications following radical hysterectomy and adjuvant radiotherapy. METHODS: From September 1992 to December 1998, 67 patients with lymph node negative uterine cervical cancer (FIGO stage distribution: 50 Ib. 17 IIa), who had undergone radical hysterectomy and postoperative adjuvant radiotherapy with a minimum of three years of follow-up were evaluated. All patients received 50-58 Gy of external radiation to the lower pelvis followed by two sessions of intravaginal brachytherapy with a prescribed dose of 7.5 Gy to the vaginal mucosa. For 21 patients with lymphovascular invasion, the initial irradiation field included the whole pelvis for 44 Gy. The data were analyzed for actuarial survival (AS), pelvic relapse-free survival (PRFS), distant metastasis-free survival (DMFS), and treatment-related complications. Multivariate analysis was performed to assess the prognostic factors. RESULTS: The respective five-year AS, PRFS, and DMFS for the 67 patients were 79%, 93% and 87%. Multivariate analysis identified two prognostic factors for AS: bulky tumor vs non-bulky tumor (p = 0.003), positive resection margin (p = 0.03). The independent prognostic factors for DMFS was bulky tumor (p = 0.003), while lymphatic permeation showed marginal impact to DMFS (p = 0.08). The incidence of RTOG grade 1-4 rectal and non-rectal gastrointestinal complication rates were 20.9% and 19.4%, respectively. The independent prognostic factor for gastrointestinal complication was age over 60 years (p = 0.047, relative risk 4.1, 95% CI 1.2 approximately 11.7). The incidence of non-rectal gastrointestinal injury for the patients receiving whole pelvic radiation and lower pelvic radiation was 28.5% and 15.2%, respectively (p = 0.25). CONCLUSION: For patients with lymph node negative cervical cancer following radical hysterectomy, adjuvant lower pelvic radiation appears to be effective for pelvic control. It is also imperative to intensify the strategies of adjuvant therapy for some subgroups of patients.     

How important is removal of the parametrium at surgery for carcinoma of the cervix?

OBJECTIVES: The aims of this study were (1) to determine the incidence and factors predictive for pathologic parametrial involvement in clinical stage IA1/2 and IB1 cervical cancer after radical surgery and (2) to identify a population at low risk for pathologic parametrial involvement. METHODS: All patient information was collected prospectively and extracted from a cervical cancer radical surgery database. Selection criteria for surgery were generally based upon tumor size, with the cutoff for surgery between 3 and 4 cm. Parametrial involvement (PI) was defined as either positive parametrial lymph nodes (PMLN) or malignant cells in the parametrial tissue (PT) (including lymphovascular channels) by either contiguous or discontiguous spread. Statistical analysis included the chi2 test, the Wilcoxon rank test, and the Mantel-Haentzel test. RESULTS: Between July 1984 and January 2000, 842 patients underwent radical surgery for clinical stage IA1/2 and IB1 cervical cancer at our center. Forty-nine patients (6%) had positive pelvic lymph nodes. Thirty-three patients (4%) had pathologic PI, 8 in the PMLN and 25 in the PT (none had both). PI was associated with older age (42 vs 40 years, P < 0.04), larger tumor size (2.2 vs 1.8 cm, P < 0.04), higher incidence of capillary-lymphatic space invasion (85% vs 45%, P = 0.0004), tumor grades 2 and 3 (95% vs 65%, P = 0.001), greater depth of invasion (18.0 vs 5.0 mm, P < 0.001), and pelvic lymph node metastases (44% vs 5%, P < 0.0001). The incidence of PI in patients with tumor size < or =2 cm, negative pelvic lymph nodes, and depth of invasion < or =10 mm was 0.6%. CONCLUSION: Pathologic parametrial involvement in clinical stage IA1/2 and /IB1 cervical cancer is uncommon. Acknowledging that almost all patients with pelvic lymph node metastases and a high proportion of patients with tumor invasion >10 mm will receive adjuvant radiation regardless of the radicality of surgery, a population at low risk for pathologic parametrial involvement can be identified. These patients are worthy of consideration for studies of less radical surgery performed in conjunction with pelvic lymphadenectomy.     

Blood Transfusion and the Risk of Recurrence in Stage IB Cervical Cancer

The objective of this study is to determine if perioperative blood transfusions increase the risk of recurrence in stage IB cervical cancer. Medical records from all patients with FIGO stage IB cervical cancer undergoing radical hysterectomy and pelvic lymphadenectomy (RH + PLND) at the University of Iowa and the University of Nebraska from 1978 to 1990 were retrospectively reviewed. Data collected included patient age, body mass index (BMI), tumor size, cell type, depth of cervical invasion (DOI), presence of capillary-lymphatic space involvement (CLSI), lymph node metastasis, operating time, estimated blood loss, transfusion, and follow-up data. Three hundred two patients underwent RH + PLND. Transfusions were given to 244 (81%), with a mean of 2.6 units (range 1-18 units). Median follow-up was 49.5 months (range 9-190 months). Twenty patients (6.6%) had pelvic nodal metastasis. There were no periaortic nodal metastases in the 101 patients who had periaortic nodes dissected. There were no significant differences between the transfused and nontransfused groups, with respect to age, BMI, DOI, or pelvic node metastasis. Transfused patients differed significantly from the nontransfused in that they had larger tumors (P = 0.047), more frequent CLSI (P = 0.013), longer procedures (P = 0.02), and greater estimated blood loss (P < 0.0001). Recurrences developed in 29 patients (19 pelvic, 7 lung, 3 bone). There is no difference in disease-free survival (DFS) or calculated projected survival between the transfused and nontransfused groups. Pelvic node metastasis and tumor size were independent poor prognosticators. After controlling for these factors, the number of blood transfusions was not predictive of recurrence or survival. Perioperative transfusions do not increase the risk of recurrence in patients with cervical cancer.     

Pelvic insufficiency fracture after pelvic irradiation in uterine cervix cancer

OBJECTIVES: Pelvic insufficiency fractures (IF) are well known but uncommon and are frequently misinterpreted sequelae. The clinical features were investigated. METHODS: Four hundred sixty-three patients, who were treated between 1994 and 2000 for uterine cervix cancer, were clinically examined. All patients had been treated with 10 or 15 MV photons, with 50.4-55.8 Gy in 28 fractions with adjuvant intent (n = 235) in addition to high-dose-rate brachytherapy 24 Gy in 6 fractions for curative treatment (n = 228). The median follow-up was 38 months. RESULTS: Eight patients (8/463, 1.7%) developed pelvic IF 7-19 months (median, 12 months) after the treatment. Among these, seven patients (7/228, 3.1%) were treated with curative intent and one (1/235, 0.4%) was treated with adjuvant intent. All patients were postmenopausal and complained of moderate to severe pelvic pain, which resolved after 1-11 months with conservative therapy in all patients. Two of these patients also had radiation proctitis. CONCLUSION: In women who present with pelvic pain after radiotherapy for cervical cancer, bony destruction and fractures may be indicative of a late radiation effect rather than osseous metastasis. IF are more common in the curative treatment group than in the postoperative adjuvant group.     

Vaginal radiation brachytherapy to reduce central recurrence after radical hysterectomy for cervical carcinoma

Seventeen (17%) of one hundred and two patients were treated with radiation brachytherapy (without external-beam therapy) to the proximal vagina to reduce the possibility of central pelvic recurrence following radical hysterectomy for cervical carcinoma. The 17 were considered to be at greater risk of developing recurrent cancer in the central pelvis because the cancer invaded halfway through the cervix; however, no lesions extended beyond the cervix, nor were metastases to lymph nodes present or surgical margins involved. The brachytherapy treatment was evaluated for prevention of central pelvis recurrence and for related complications. The 17 women treated with radiation brachytherapy were also compared with 74 patients who did not receive brachytherapy after radical hysterectomy because their cancers were smaller and did not invade halfway through the cervix. Both groups were similar with respect to age (41 and 40 years, respectively), weight (69.5 and 65.9 kg), operative characteristics, and the proportions of squamous cell carcinoma and adenocarcinoma. Recurrences have not been observed among the patients treated with brachytherapy during a mean follow-up of 39 months (range, 9-92 months). No complications were attributed to the brachytherapy. However, two patients with large tumors refused adjuvant brachytherapy and suffered central pelvic recurrences. Brachytherapy in selected patients following radical hysterectomy was safely administered and appeared to reduce the risk of central pelvic recurrence.     

Clinical and histopathologic factors predicting recurrence and survival after pelvic exenteration for cancer of the cervix

Between September 1969 and January 1, 1986, 143 pelvic exenterations for recurrent cervical cancer were performed by the gynecologic oncologists at the University of Alabama at Birmingham. Of this group, 78 patients underwent total pelvic exenteration, 63 patients had anterior exenteration, and two had posterior exenteration. The overall operative mortality rate was 6.3%, mostly associated with total pelvic exenteration. The 5-year survival rates were 50% overall, 63% with anterior exenteration and 42% with total exenteration. Univariate and multivariate analyses were performed to identify clinical and histopathologic factors predictive of prolonged survival. Using three clinical factors (duration from initial radiation therapy to exenteration, size of the central mass, and presence of preoperative sidewall fixation), low-, intermediate-, and high-risk groups were constructed; the 5-year survival rates for these groups were 82, 46, and 0%, respectively. Inclusion of one histopathologic factor (margin status of the surgical specimen) added to the ability to predict 2- and 5-year survival rates. The best candidates for cure by pelvic exenteration were those with recurrent small (less than 3 cm), mobile central masses who were a year or longer from the time of their previous radiation therapy. Attempts to resect bulky pelvic recurrences that impinge on the pelvic sidewall, especially in the case of persistent or early recurrent disease (within 6 months), or continuation of exenterative procedures in women known to have nodal metastases or extrapelvic spread, are generally futile. For those women falling between the two extremes, sound clinical and operative judgment is imperative in regard to selecting the treatment offering the best quality of life.     

Postoperative radiotherapy in stage IB squamous cell cervical cancer

OBJECTIVE: The purpose of the study was to evaluate postoperative whole pelvic radiation for high-risk patients with FIGO Stage IB cervical cancer. METHODS: One hundred and forty-eight patients with Stage IB squamous cell carcinoma of the cervix underwent radical hysterectomy and pelvic lymphadenectomy. The low-risk group included patients without unfavorable prognostic factors who were treated only by surgery. The high-risk group included women with pelvic node metastases, with positive or close surgical margins, clinical tumor size > 4.0 cm, depth of stromal invasion > 1/3 the cervical wall, grade 3 tumor and presence of lymphovascular space involvement. High-risk patients received whole pelvic radiotherapy between two and four weeks after surgery. RESULTS: Seventy patients (47.3%) were low risk and 78 patients (52.7%) were high risk. Locoregional recurrences were diagnosed in nine cases (12.8%) in the surgery group and in 11 patients (14.1%) assigned to radiotherapy. The incidence of distant metastases was 2.8% in the surgery group and 6.4% in the surgery and radiotherapy group. Overall survival at five years was 88.6% in the low-risk group and 84.7% in the high-risk group. CONCLUSION: Five-year overall survival, locoregional and distant metastases were similar in the low-risk and high-risk groups of patients, thus emphasizing the value of whole pelvic radiation in patients with unfavorable prognostic factors in Stage IB cervical cancer.     

Radiation-associated endometrial cancers are prognostically unfavorable tumors: a clinicopathologic comparison with 527 sporadic endometrial cancers

INTRODUCTION: Previous reports have suggested that patients who have undergone pelvic radiation for cervical cancer are at risk for developing poorly differentiated endometrial cancers with poor prognoses. MATERIALS AND METHODS: We conducted a retrospective chart and histologic review of patients from Memorial Sloan-Kettering Cancer Center and MD Anderson Cancer Center diagnosed with endometrial cancer after radiation therapy (RT) for cervical cancer from 1976 to 2000. The comparison group comprised MSKCC endometrial cancer patients whose tumors were not radiation associated ("sporadic cancers"). RESULTS: We identified 23 patients who developed endometrial carcinoma or carcinomasarcoma after RT for cervical carcinoma and 527 sporadic endometrial cancer patients. When radiation-associated endometrial cancers (RAECs) were compared with sporadic cancers, significant differences were noted with regard to stage, grade and histologic subtype distribution. In the RAEC group, there were 16 (70%) stages III and IV cancers compared with 101 (19%) in the sporadic group (P<0.001). There were 20 (87%) grade 3 cancers in the RAEC group versus 161 (31%) in the sporadic group (P<0.001). There were 16 (70%) high-risk histologic subtypes (serous, clear cell, carcinosarcoma, undifferentiated) in the RAEC group versus 79 (15%) in the sporadic group (P<0.001). Median survival in the RAEC group was 24 months versus not reached in the sporadic group (P<0.001). Radiation remained a significant factor for poor prognosis in a stratified analysis, in which we compared sporadic and RAEC cancers controlled for age, histology, grade and stage. However, radiation lost significance in a multivariate analysis, in which stage- and grade-matched cancers from both groups were compared. DISCUSSION: The clinicopathologic characteristics of RAECs, which include a preponderance of high-stage, high-grade and high-risk histologic subtypes, indicate that these tumors differ from sporadic endometrial carcinomas. However, patients with RAECs do not appear to have a significantly worse prognosis when compared with patients with high-stage and high-grade sporadic cancers.     

Relapse patterns in FIGO stage IB carcinoma of the cervix

Site of recurrence and survival data were reviewed for 96 patients with FIGO stage IB cervical carcinoma treated between July 1978 and December 1986 with radical surgery (N = 55), radiation therapy (N = 30), or combination therapy (N = 11). There were 21 patients (21.8%) who suffered recurrences. After radiation 10 of 30 (33.3%) patients recurred versus 11 of 55 (20%) after radical surgery alone. Recurrences were observed in 6 of 14 (42.8%) patients with positive nodes, 11 of 61 (18%) patients with negative nodes, and 4 of 21 (19%) patients with unknown nodal status. The first manifestation of recurrence was central in 3, locoregional in 9, and distant in 9. The median disease-free interval (DFI) was 11 months for surgical and 10.5 months for irradiated patients. The 2-year disease-free survival was 83.6% for surgical patients and 73.3% for irradiated patients. The risk of distant metastases was 3 of 55 (5.4%) following radical surgery and 6 of 30 (20%) after radiation (P = 0.04). The median time to pelvic recurrence was 10 months and that for distant recurrence was 20 months (P less than 0.05). The median time to pelvic relapse was 9.5 months for radical surgery patients and 10 months for irradiated patients. The median time to distant recurrence was 20 months for radical surgery patients and 16.5 months for irradiated patients. Median survival in those who died of disease after a recurrence confined to the pelvis was 15 months versus 8 months for those with a distant recurrence (P less than 0.05). Our data confirm that (1) site of relapse is influenced by primary therapeutic modality and (2) pelvic recurrence manifests before distant recurrence; however, median DFI for all recurrences as well as for the subsets of pelvic and distant relapses is independent of primary modality. We suggest that an understanding of the natural history of cervical cancer recurrence will allow optimal use of resources in the follow-up of patients to detect recurrence.     

Survival of nonsurgically staged patients with negative lymphangiograms who had Stage IIB carcinoma of the cervix treated by pelvic radiation plus hydroxyurea

Twenty patients with Stage IIB carcinoma of the cervix who did not undergo pretherapy para-aortic lymphadenectomy, but who had negative preradiation therapy lymphangiograms, were treated with pelvic radiation plus hydroxyurea. Patients received a median of 5020 rads of pelvic radiation plus 4000 rads of radium to point A. During radiation therapy and for a total of 12 weeks, patients received hydroxyurea administered at a dose of 80 mg/kg of body weight every 3 days if the white blood cell count was greater than or equal to 2,500/mm3 and platelets were greater than or equal to 75,000/mm3. The median follow-up time was 28 months (6 to 83 months). The estimated 5-year survival rate was 92%. Seventeen patients are alive with no evidence of disease (median, 28 months); one died of intercurrent disease with no evidence of disease (17 months); one is alive with no evidence of disease after recurrence (18 months); and one died of cervical cancer (22 months). The survival rate of patients with nonsurgically staged negative pretherapy lymphangiograms who had Stage IIB cervical cancer treated by pelvic radiation therapy plus hydroxyurea approximated the improved survival rate reported for patients with negative pretherapy para-aortic lymphadenectomy who were treated with pelvic radiation therapy plus hydroxyurea. Both studies would suggest that pelvic radiation plus hydroxyurea improves the rate of survival in patients with Stage IIB cervical cancer.     

Radiation injury to intestine following hysterectomy and adjuvant radiotherapy for cervical cancer

OBJECTIVE: To evaluate the risk factors for nonrectal radiation-induced intestinal injury (NRRIII) following adjuvant radiotherapy (RT) for cervical cancer using a retrospective review of medical records. METHODS: From September 1992 to December 1998, 164 patients with uterine cervical cancer that had completed their allocated adjuvant radiotherapy at the Chinese Medical University Hospital were enrolled for NRRIII analysis. The patients were classified into two groups according to the extent of surgery. Group A consisted of 110 patients (International Federation of Gynecology and Obstetrics [FIGO] stage: IB, n = 87; IIA, n = 21; IIB, n = 2) undergoing radical hysterectomy and bilateral pelvic lymph node dissection, while Group B was composed of 54 analogs receiving adjuvant radiotherapy following incident extrafascial hysterectomy. Treatment consisted of external beam radiotherapy (EBRT) and high-dose-rate intravaginal brachytherapy (HDRIVB). Initially, the whole pelvis was treated with 10 MV X-rays. After irradiation (44 Gy in 22 fractions over 4-5 weeks), the field was limited to the true pelvis and a further 10-20 Gy delivered in 5-10 fractions. For 21 patients in group A without pelvic lymph node metastasis or lymphovascular invasion, the radiation field was confined to the lower pelvis, with a prescribed dose of 50-58 Gy delivered over 5-6 weeks. HDRIVB was performed using an Ir-192 remote after-loading technique at 1-week intervals. A total of 159 patients (97%) received two insertions, while 5 had only one. The standard prescribed HDRIVB dose was 7.5 Gy to the vaginal surface. Logistic regression analysis was performed for assessment of the factors associated with NRRIII. RESULTS: After 38-119 months of follow-up (median, 60), 22 patients (13.4%) developed Radiation Therapy Oncology Group (RTOG) grade 2 or greater NRRIII at a median latency of 18 months (range, 5-48). Four patients were diagnosed as grade 3 complications requiring surgery and three had expired. The independent factors for NRRIII were radical hysterectomy (P = 0.04, relative risk 2.45), lower-pelvic dose >54 Gy (P = 0.0001, relative risk 10.27), and age over 60 years (P = 0.001, relative risk 5.45). The incidence of NRRIII for patients receiving whole and lower-pelvic irradiation was 14.5% and 10.6%, respectively (P = 0.45). Although there was no statistical significance comparing the two external beam irradiation strategies in terms of NRRIII, all four patients with grade 3 NRRIII underwent whole pelvic irradiation. CONCLUSION: This study identifies three predictive factors for the development of NRRIII following adjuvant radiotherapy for cervical cancer. Limiting the EBRT dose to less than 54 Gy, meticulous patient selection in the elderly, careful planning of the irradiated field, and the constraint of vaginal brachytherapy are four approaches to optimization of postoperative adjuvant radiotherapy.     

单中心559例卵巢癌患者淋巴结转移的危险因素分析与淋巴结切除术临床决策探讨#br#

【Abstract】?Objective?To review the data of patients with ovarian cancer, analyze the related factors of pelvic lymph node metastasis (PLNM) and para-aortic lymph node metastasis (PALNM), and establish a predictive model, so as to provide suggestions for clinical practice. Methods?The clinicopathological data of 559 patients with ovarian cancer treated in Chinese PLA General Hospital from January 2014 to January 2019 were retrospectively analyzed. The risk factors affecting PLNM and PALNM were analyzed by univariate and logistic regression, and the prediction model was established. Results?Among 559 ovarian cancer patients, pelvic lymph node metastasis was found in 205 cases (36.67%) and abdominal para-aortic lymph node metastasis in 117 cases (20.93%). The independent risk factors affecting PLNM were bilateral lesions (OR=2.278, 95%CI: 1.433~3.621), pelvic metastases (OR=1.801, 95%CI: 1.154~2.810), and abdominal metastases (OR=4.177, 95%CI: 2.597~6.717) and appendiceal metastasis (OR=2.332, 95%CI: 1.389~3.915); The independent risk factors affecting PALNM were appendiceal metastasis (OR=2.324, 95%CI: 1.383~3.906) and PLNM (OR=7.629, 95%CI: 4.615~12.610). Age (≥55 years) (OR=0.566, 95%CI: 0.350~0.915) was the protective factor. The ROC curve AUC of PLNM and PALNM was 0.803 (95%CI: 0.767~0.840) and 0.793 (95%CI: 0.745~0.841), respectively. Conclusion?Bilateral lesions, pelvic metastases, intraperitoneal metastases and appendiceal metastases were independent risk factors for PLNM in ovarian cancer patients. Appendiceal metastasis and PLNM were independent risk factors for PALNM, and age (≥55 years) was the protective factor.     

Comparison of gracilis and rectus abdominis myocutaneous flap neovaginal reconstruction performed during radical pelvic surgery: flap-specific morbidity

To compare flap-specific complications of gracilis myocutaneous (GM) and rectus abdominis myocutaneous (RAM) flap neovaginal reconstructions after radical pelvic surgery. The study was a single-institution retrospective review of patients undergoing concurrent radical pelvic surgery with GM or RAM neovaginal reconstructions performed on a gynecological oncology service, 1978-2003. Flap-specific complications were compared between the techniques. Forty-four GM and 32 RAM neovaginal reconstructions were analyzed: plastic surgeons developed 12 (27%) GM and 4 (13%) RAM flaps, with all other flaps performed by gynecological oncologists. Primary procedures included 54 (71%) total pelvic exenterations, with partial exenterations or radical vulvovaginectomies in 16 (21%) and 6 (8%) patients, respectively. Forty (53%) patients had received radiation and 28 (36%) received chemoradiation before radical surgery. There were no significant differences in patient characteristics, other than more frequent use of continent urinary conduits (P < 0.001) and a trend for more frequent sidewall radiation (P < 0.1) in the RAM group, reflecting use in more recent patients (P < 0.001). Median follow-up is 28 months (range: 2 weeks to 216 months), with 5% acute operative mortality. Flap-specific complications were significantly increased in GM patients (P < 0.03). Overall flap loss was significantly increased in GM patients (P < 0.02). Thirty (59%) of 51 patients surviving for more than 12 months reported coitus, with no significant difference between the groups. Because of lower overall incidence of flap-specific complications and significantly lower incidence of flap loss compared with GM flap, RAM flap has become our technique of choice for neovaginal reconstruction concurrent with radical pelvic surgery.