Bone Marrow-sparing Intensity Modulated Radiation Therapy With Concurrent Cisplatin For Stage IB-IVA Cervical Cancer: An International Multicenter Phase II Clinical Trial (INTERTECC-2).

PURPOSE: To test the hypothesis that intensity modulated radiation therapy (IMRT) reduces acute hematologic and gastrointestinal (GI) toxicity for patients with locoregionally advanced cervical cancer. METHODS AND MATERIALS: We enrolled patients with stage IB-IVA cervical carcinoma in a single-arm phase II trial involving 8 centers internationally. All patients received weekly cisplatin concurrently with once-daily IMRT, followed by intracavitary brachytherapy, as indicated. The primary endpoint was the occurrence of either acute grade ≥3 neutropenia or clinically significant GI toxicity within 30 days of completing chemoradiation therapy. A preplanned subgroup analysis tested the hypothesis that positron emission tomography-based image-guided IMRT (IG-IMRT) would lower the risk of acute neutropenia. We also longitudinally assessed patients' changes in quality of life. RESULTS: From October 2011 to April 2015, 83 patients met the eligibility criteria and initiated protocol therapy. The median follow-up was 26.0 months. The incidence of any primary event was 26.5% (95% confidence interval [CI] 18.2%-36.9%), significantly lower than the 40% incidence hypothesized a priori from historical data (P=.012). The incidence of grade ≥3 neutropenia and clinically significant GI toxicity was 19.3% (95% CI 12.2%-29.0%) and 12.0% (95% CI 6.7%-20.8%), respectively. Compared with patients treated without IG-IMRT (n=48), those treated with IG-IMRT (n=35) had a significantly lower incidence of grade ≥3 neutropenia (8.6% vs 27.1%; 2-sided χ2P=.035) and nonsignificantly lower incidence of grade ≥3 leukopenia (25.7% vs 41.7%; P=.13) and any grade ≥3 hematologic toxicity (31.4% vs 43.8%; P=.25). CONCLUSIONS: IMRT reduces acute hematologic and GI toxicity compared with standard treatment, with promising therapeutic outcomes. Positron emission tomography IG-IMRT reduces the incidence of acute neutropenia.

Clinical Outcomes of Computed Tomography-Based Volumetric Brachytherapy Planning for Cervical Cancer.

PURPOSE/OBJECTIVES: A report of clinical outcomes of a computed tomography (CT)-based image guided brachytherapy (IGBT) technique for treatment of cervical cancer. METHODS AND MATERIALS: Seventy-six women with International Federation of Gynecology and Obstetrics stage IB to IVA cervical carcinoma diagnosed between 2007 and 2014 were treated with definitive external beam radiation therapy (EBRT) with or without concurrent chemotherapy followed by high-dose-rate (HDR) IGBT. All patients underwent planning CT simulation at each implantation. A high-risk clinical target volume (HRCTV) encompassing any visible tumor and the entire cervix was contoured on the simulation CT. When available, magnetic resonance imaging (MRI) was performed at implantation to assist with tumor delineation. The prescription dose was prescribed to the HRCTV. RESULTS: The median follow-up time was 17 months. Thirteen patients (17%) had an MRI done before brachytherapy, and 16 patients (21%) were treated without MRI guidance. The mean EBRT/IGBT sum 2-Gy equivalent dose (EQD2) delivered to the 90% volume of the HRCTV was 86.3 Gy. The mean maximum EQD2s delivered to 2 cm(3) of the rectum, sigmoid, and bladder were 67.5 Gy, 66.2 Gy, and 75.3 Gy, respectively. The 2-year cumulative incidences of local, locoregional, and distant failure were 5.8% (95% confidence interval [CI]: 1.4%-14.8%), 15.1% (95% CI: 5.4%-29.4%), and 24.3% (95% CI: 12.1%-38.9%), respectively. The 2-year overall and disease-free survival rates were 75% (95% CI, 61%-91%) and 73% (95% CI, 60%-90%), respectively. Twenty-nine patients (38%) experienced grade ≥ 2 acute toxicity, with 5 cases of acute grade 3 toxicity and no grade ≥ 4 toxicities. One patient experienced grade 3 gastrointestinal toxicity. No other late grade ≥ 3 events were observed. CONCLUSIONS: This is the largest report to date of CT/MRI-based IGBT for the treatment of cervical cancer. The results are promising, with excellent local control and acceptable toxicity. Further investigation is needed to assess the long-term safety and efficacy of this treatment.

Uterine sarcomas and parasitic myomas after laparoscopic hysterectomy with power morcellation.

OBJECTIVE: The purpose of this study was to describe the incidence and risk factors for uterine sarcomas and parasitic myomas at the time of power morcellation. STUDY DESIGN: We performed a retrospective review of 3523 women who underwent laparoscopic hysterectomy from 2001-2012. Univariate analyses were used for the morcellation cases to identify potential risk factors. Multivariable logistic regression was performed. RESULTS: Nine hundred forty-one patients underwent power morcellation at the time of hysterectomy; 10 of 941 patients (1.1%) were diagnosed subsequently with uterine sarcomas or parasitic myomas. The overall incidence of uterine sarcoma was 6 of 941 (0.6%), with a median age of 47 years (range, 41-52 years). There was no association among any of the factors analyzed and uterine sarcoma. Three of 6 patients had sarcoma diagnosed on initial pathologic evaluation of the morcellated specimen; 3 patients had delayed diagnosis of sarcoma with benign disease at the time of the initial procedure (median time to second evaluation, 6 years). For parasitic myomas (n=4), the median age was 35 years (range, 32-40 years), and the median time to second evaluation was 5 years. On multivariate analysis, age<40 years (odds ratio, 26; 95% confidence interval, 2.7015-261.9; P≤.01) was associated with higher risk of the development of parasitic myomas. CONCLUSION: Uterine sarcoma was found in 0.6% of patients who underwent power morcellation but was not found to be associated significantly with any preoperative factors. All 6 cases were noted to have apparent fibroid tumors as an indication for their hysterectomy. Age<40 years was a risk factor for parasitic myomas after power morcellation. Patients should be counseled about these complications before power morcellation.

Is atypical squamous cells that cannot exclude high-grade squamous intraepithelial lesion clinically significant?

OBJECTIVE: To determine the cumulative risk of cervical intraepithelial neoplasia (CIN) 2 or 3 in patients with atypical squamous cells, cannot exclude HSIL (ASC-H). METHODS: A retrospective analysis was performed to identify patients referred to the dysplasia clinic with ASC-H. Initial evaluation included colposcopy, endocervical curettage, and an ectocervical biopsy, when indicated, in all the patients. A follow-up evaluation was performed at 6 and 12 months. Cumulative histological diagnosis of CIN 2 or 3 at 12 months served as the clinical end point. RESULTS: Two hundred twenty-nine patients with ASC-H and with a mean age of 32.8 years were evaluated. At the time of initial colposcopy, only 10.0% (23/229; 95% CI = 6.5%-15%) of the patients had histological evidence of CIN 2 or 3. The cumulative risk of CIN 2 or 3 was 12.2% (95% CI = 8%-17%). CONCLUSIONS: Evaluation of patients with ASC-H with colposcopy does lead to the detection of CIN 2 or 3 but perhaps at a rate lower than previously reported.

Far forward gynecologic care of the female soldier.

OBJECTIVE: To evaluate the value, unit cost and medical effectiveness of providing specialized obstetric and gynecologic care far forward, at echelon III, the combat support hospital (CSH), in the operating theater of Afghanistan during Operation Enduring Freedom (OEF), rotation 5. STUDY DESIGN: Between April 2004 and September 2004, records were reviewed from the outpatient gynecology clinic at Bagram Air Field (BAF), in Afghanistan, through an approved protocol request. Cohort analysis was performed on all gynecologic patients. Significant differences in distribution of clinical factors were determined by Student's t test. RESULTS: A total of 62 cases were extracted for analysis over the 6-month period. Fifty-seven total patients were seen at echelon III, the CSH at BAF, while 5 were sent to level IV or V echelon care in Landstuhl, Germany. The average distance traveled for the patients coming to BAF was 158 km, while those sent to Germany averaged 5,204 km. The mean travel time in days was significantly lower among patients seen at BAF, 0.5 versus 7 days for patients sent to Germany. The time to appointment was also significantly lower among those patients seen at BAF: 0.04 versus 13 days for patients sent to Germany. CONCLUSION: We devised and implemented the concept of far forward specialized gynecologic care for women participating in OEF. This substantially decreased the woman-hours lost by their individual units. The far forward availability of gynecologic care and the supplies to evaluate and treat abnormal Pap smears should be considered by all military services in their plans for providing health care for the modern female soldier.

Survival of patients with untreated cervical carcinoma.

Patients infrequently present with advanced-stage cervical malignancy in the United States, where access to care and aggressive screening, detection, and treatment regimens are the standard. Neglected cancer is more likely in countries with underdeveloped healthcare delivery systems; yet in this new millennium, we foresee not only an aging population with modern medicine able to prolong life expectancy, but also attentive screening regimens even amid the older old. Taking into account common comorbid illness from which patients used to die, informed consent in making a treatment in the robust and frail elderly becomes a new challenge. Recognizing an ever-growing population in today's culture of patient-directed care, clinicians may find patients choosing alternative modalities or simply declining conventional therapies. The difficult dilemma then arises about how to inform a patient most accurately of her prognosis in an untreated condition. In the past, virtually all patients in the United States traditionally received some treatment for cervical cancer on diagnosis; thus, review was made of archival published literature to document survival of patients with untreated cervical cancer.

Loop excision for high-grade squamous intraepithelial lesion on cytology: correlation with colposcopic and histologic findings.

OBJECTIVE: Our purpose was to examine the correlation between colposcopic and histologic findings in patients who have undergone loop electrosurgical excision of the cervix (LEEP) for high-grade dysplasia on cytology without prior colposcopically directed biopsy. STUDY DESIGN: A retrospective review was performed of all patients who underwent LEEP for high-grade squamous intraepithelial lesion (HGSIL) on Papanicolaou (Pap) smear without a prior cervical biopsy over a 17-month period. We correlated the histologic result with colposcopic findings at the time of LEEP. RESULTS: Of 104 patients undergoing LEEP, 63 patients (61%) had cervical intraepithelial neoplasia (CIN) grade 2 or greater. Thirty-four (54%) of these 63 patients with histologically proved high-grade dysplasia had a normal or low-grade colposcopic examination. There were 10 patients with CIN 1 to CIN 1-2 and 1 patient with microinvasive squamous cell carcinoma. CONCLUSION: Despite lack of correlation between colposcopic and histologic results, HGSIL on Pap smear is an appropriate indication for LEEP.

Adenosquamous histology predicts a poor outcome for patients with advanced-stage, but not early-stage, cervical carcinoma.

BACKGROUND: The objective of this study was to compare survival between patients with adenocarcinoma and patients with adenosquamous carcinoma of the cervix. METHODS: Patients who were diagnosed with invasive cervical carcinoma from 1988 to 1999 were identified from the Automated Central Tumor Registry for the United States Military Health Care System. Clinical data, including race, age at diagnosis, histology, tumor grade, disease stage, lymph node status, treatment modality, and survival, were collected. Survival analysis was performed with Kaplan-Meier survival curves and compared using the log-rank test. RESULTS: A total of 273 women were identified, 185 women with a histologic diagnosis of adenocarcinoma (AC) and 88 women with a diagnosis of adenosquamous carcinoma (ASC). Among the women with ASC, only 5% had Grade 1 tumors, and 66% had Grade 3 tumors. By comparison, among the women with AC, 37% had Grade 1 tumors, and 26% had Grade 3 tumors (P < 0.001). There was no difference in the incidence of positive lymph nodes or in the number of patients who underwent radical hysterectomy as primary treatment between patients with ASC and patients with AC. More patients with ASC received radiation therapy (51% vs. 28%) or chemotherapy (29% vs. 12%) as treatment (P < 0.001). Patients who had tumors with ASC histology had a significantly decreased 5-year survival rate compared with patients who had tumors with AC histology (65% vs. 83%; P < 0.002). When patients with early-stage cervical carcinoma (International Federation of Gynecology and Obstetrics [FIGO] Stage I) were examined separately, there was no statistically significant difference in the 5-year survival rate (AC, 89%; ASC, 86%; P = 0.644). However, when patients with advanced-stage disease (FIGO Stages II-IV) were analyzed, ASC was associated with a significant decrease in median and overall survival (P = 0.01). When the results were analyzed by grade, patients who had tumors with ASC histology had a shorter survival compared with patients who had AC histology of any grade; however, this was a significant difference only for patients with Grade 1 tumors: The 5-year survival rate for patients with Grade 1 AC was 93%, compared with 50% for patients with Grade 1 ASC (P < 0.01). CONCLUSIONS: ASC histology appears to be an independent predictor of poor outcome in women with cervical carcinoma compared with their counterparts who have pure AC. The significant decrease in survival was observed only in patients with advanced-stage cervical carcinoma. This decreased survival may be related mainly to the grade of ASC.