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1.  Adaptive 3D Image-Guided Brachytherapy: A Strong Argument in the Debate on Systematic Radical Hysterectomy for Locally Advanced Cervical Cancer 
The Oncologist  2013;18(4):415-422.
The outcomes of patients with locally advanced cervical cancer treated with three-dimensional image-guided brachytherapy after concomitant chemoradiation were evaluated. An excellent locoregional control rate with low treatment-related morbidity was observed, justifying the elimination of hysterectomy in the absence of obvious residual disease.
Learning Objectives
Evaluate control rates of IGABT combined with CCRT for the treatment of locally advanced cervical cancer.Describe survival outcomes in patients treated with IGABT combined with CCRT for locally advanced cervical cancer.Describe toxicities in patients treated with IGABT combined with CCRT for locally advanced cervical cancer.
Purpose.
To evaluate the outcomes of patients with locally advanced cervical cancer treated with three-dimensional image-guided brachytherapy (IGABT) after concomitant chemoradiation (CCRT).
Materials and Methods.
Data from patients treated with CCRT followed by magnetic resonance imaging-guided or computed tomography-guided pulsed-dose-rate brachytherapy, performed according to the Groupe Européen de Curiethérapie–European Society for Radiotherapy and Oncology guidelines, were reviewed. At first, stage I or II patients systematically underwent radical hysterectomy or were offered a randomized study evaluating hysterectomy. Then, hysterectomy was limited to salvage treatment.
Results.
Of 163 patients identified, 27% had stage IB, 57% had stage II, 12% had stage III, and 3% had stage IVA disease. The mean dose delivered (in 2-Gy dose equivalents) to 90% of the high-risk clinical target volume was 78.1 ± 9.6 Gy, whereas the doses delivered to organs at risk were maintained under the usual thresholds. Sixty-one patients underwent a hysterectomy. Macroscopic residual disease was found in 13 cases. With a median follow-up of 36 months (range, 5–79 months), 45 patients had relapsed. The 3-year overall survival rate was 76%. Local and pelvic control rates were 92% and 86%, respectively. According to the Common Toxicity Criteria 3.0, 7.4% of patients experienced late grade 3 or 4 toxicity. Most of those had undergone postradiation radical surgery (2.9% vs. 14.8; p = .005).
Conclusion.
IGABT combined with CCRT provides excellent locoregional control rates with low treatment-related morbidity, justifying the elimination of hysterectomy in the absence of obvious residual disease. Distant metastasis remains an important first relapse and may warrant more aggressive systemic treatment.
doi:10.1634/theoncologist.2012-0367
PMCID: PMC3639528  PMID: 23568003
Cervical cancer; Image-guided adaptive brachytherapy; Chemoradiation; Optimization; Dose escalation
2.  Lymphocele and Ovarian Cancer: Risk Factors and Impact on Survival 
The Oncologist  2012;17(9):1198-1203.
This retrospective study describes the incidence, impact on survival, and the risk factors for symptomatic lymphoceles in patients with ovarian cancer.
Learning Objectives
After completing this course, the reader will be able to: Identify risk factors for lymphoceles after cytoreductive surgery in ovarian cancer.Describe the impact of lymphocleles on outcomes in women with ovarian cancer.
This article is available for continuing medical education credit at CME.TheOncologist.com
Introduction.
We describe the incidence, impact on survival, and the risk factors for symptomatic lymphoceles in patients with ovarian cancer.
Methods.
This retrospective study includes patients with ovarian cancer who had complete cytoreductive surgery and para-aortic and pelvic lymphadenectomy performed in our institute from 2005 to 2011. Patients were classified into two groups: patients with symptomatic lymphoceles and a control group.
Results.
During the study period, 194 patients with epithelial ovarian cancer underwent cytoreductive surgery and a lymphadenectomy without macroscopic residual disease. Fifty-four patients had symptomatic lymphoceles (28%). In the multivariate analysis, only supraradical surgery was significantly and independently associated with the risk of symptomatic lymphoceles occurring postoperatively. Median follow-up was 24.8 months (range, 1–74 months). Survival rates were not significantly different between the symptomatic lymphocele group and the control group. Two-year disease-free survival rates were 54% for the lymphocele group and 48% for the control group. Two-year overall survival rates were 90% for the lymphocele group and 88% for the control group.
Conclusions.
Symptomatic lymphoceles occur frequently after cytoreductive surgery in ovarian cancer. Supraradical surgery is an independent risk factor. The occurrence of symptomatic lymphoceles does not decrease survival. Nevertheless, further studies are needed to reduce the risk of lymphoceles in such patients.
doi:10.1634/theoncologist.2012-0088
PMCID: PMC3448413  PMID: 22707515
Lymphadenectomy; Ovarian cancer; Lymphocele; Cytoreductive surgery; Survival
3.  Results of the GYNECO 02 Study, an FNCLCC Phase III Trial Comparing Hysterectomy with No Hysterectomy in Patients with a (Clinical and Radiological) Complete Response After Chemoradiation Therapy for Stage IB2 or II Cervical Cancer 
The Oncologist  2012;17(1):64-71.
The therapeutic impact of completion surgery (hysterectomy) after chemoradiotherapy was investigated in patients with stage IB or II cervical cancer. Hysterectomy had no therapeutic impact in patients with a clinical and radiological complete response after chemoradiotherapy, but this conclusion is limited by the lack of power.
Learning Objectives
After completing this course, the reader will be able to: Evaluate the therapeutic impact of hysterectomy after chemoradiation therapy in locally advanced cervical cancer.Evaluate the rate of histologic residual disease in patients with complete clinical and radiologic response after chemoradiation therapy.
This article is available for continuing medical education credit at CME.TheOncologist.com
Background.
Concomitant chemoradiation (CRT) (including brachytherapy) is considered the standard management for stage IB2 or II cervical cancer in many countries. Nevertheless, some of them discuss completion surgery (hysterectomy [HT]) after CRT. The aim of this study was to investigate the therapeutic impact of such surgery.
Methods.
A randomized trial was opened in France in 2003 to evaluate the interest in HT after CRT. Inclusion criteria were: (a) stage IB2 or II cervical cancer without extrapelvic disease on conventional imaging; (b) pelvic external radiation therapy (45 Gy with or without parametrial or nodal boost) with concomitant cisplatin chemotherapy (40 mg/m2 per week) followed by uterovaginal brachytherapy (15 Gy to the intermediate risk clinical target volume); and (c) complete clinical and radiological response 6–8 weeks after brachytherapy. Patients were randomized between HT (arm A) and no HT (arm B). Unfortunately this trial was closed because of poor accrual: 61 patients were enrolled (in 2003–2006) and are reported on here.
Results.
Thirty one and 30 patients were enrolled, respectively, in arm A and arm B. Twelve patients recurred (five of them died): respectively, eight and four in arm A and arm B. The 3-year event-free survival rates were 72% (standard error [SE], 9%) and 89% (SE, 6%) (not significant [NS]) in arm A and arm B, respectively. The 3-year overall survival rates were 86% (SE, 6%) and 97% (SE, 3%) (NS) in arm A and arm B, respectively.
Conclusions.
Results of the current trial seem to suggest that completion HT had no therapeutic impact in patients with clinical and radiological complete response after CRT (but this conclusion is limited by the lack of power).
doi:10.1634/theoncologist.2011-0276
PMCID: PMC3267825  PMID: 22234626
Chemoradiation therapy; Surgery; Locally advanced cervical cancer; Nodal involvement; Prognostic factors; Residual disease; Survival
4.  Factors Associated with Altered Long-Term Well-Being After Prophylactic Salpingo-Oophorectomy Among Women at Increased Hereditary Risk for Breast and Ovarian Cancer 
The Oncologist  2011;16(9):1250-1257.
Factors associated with long-term altered well-being after prophylactic bilateral salpingo-oophorectomy, namely, lower quality of life, altered sexual functioning, greater anxiety, and more endocrine symptoms, were identified.
Learning Objectives
After completing this course, the reader will be able to: Describe factors associated with decreased well-being after PBSO in order to prospectively identify patients at risk.Provide pre-operative counseling and information to patients at risk of decreased well-being after PBSO.
This article is available for continuing medical education credit at CME.TheOncologist.com
Background.
Prophylactic bilateral salpingo-oophorectomy (PBSO) might alter several components of well-being, such as sexual functioning and endocrine symptoms, in women at high risk for hereditary breast and/or ovarian cancer, compared with the general population. We searched for factors associated with altered long-term well-being in this population (lower quality of life [QOL], altered sexual functioning, greater anxiety, more endocrine symptoms).
Methods.
All high-risk women who had undergone PBSO during the past 15 years in a single cancer center were contacted by mail. Upon acceptance, they were sent five questionnaires: (a) general social questions, (b) the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, (c) Sexual Activity Questionnaire, (d) Functional Assessment of Cancer Therapy – Endocrine Symptom, and (5) State-Trait Anxiety Inventory. Logistic analyses were used to identify factors associated with altered results. Because of multiple testing, only p-values ≤ .01 were considered significant.
Results.
One hundred twelve of 175 women (64%) returned the completed questionnaires at a mean duration (standard deviation) of 6.0 (5.1) years after PBSO. QOL was positively influenced by two baseline factors: a high educational level and occupying an executive position. However, younger age at PBSO was associated with lower social functioning and greater anxiety. At the time of the study, practicing a sport and the avoidance of weight gain (≥10%) were highly related to QOL, sexual pleasure, endocrine symptoms, and anxiety in the univariate analysis and predictive of better QOL and lower anxiety in the multivariate analysis.
Conclusions.
Younger women and women with a low educational level and no occupation appear to be at higher risk for altered long-term well-being. After surgery, practicing a sport and stable weight may help maintain overall well-being.
doi:10.1634/theoncologist.2010-0336
PMCID: PMC3228172  PMID: 21765195
Quality of life; BRCA; Hereditary breast and ovarian cancer; Prophylactic oophorectomy; Menopause; Sexual function
5.  Analysis of Morbidity and Clinical Implications of Laparoscopic Para-Aortic Lymphadenectomy in a Continuous Series of 98 Patients with Advanced-Stage Cervical Cancer and Negative PET–CT Imaging in the Para-Aortic Area 
The Oncologist  2011;16(7):1021-1027.
A series of patients with locally advanced cervical cancer, with no positive para-aortic nodes on positron emission tomography–computed tomography who had undergone a primary laparoscopic para-aortic lymphadenectomy was retrospectively reviewed. Morbidity was limited and the completion of treatment was not delayed when complications occurred.
Background.
Laparoscopic para-aortic lymphadenectomy (PAL) is being used increasingly to stage patients with locally advanced cervical cancer (LACC) and to define radiation field limits before chemoradiation therapy (CRT). This study aimed to define clinical implications, review complications, and determine whether surgical complications delayed the start of CRT.
Methods.
We retrospectively reviewed a continuous series of patients with LACC, with no positive para-aortic (PA) nodes on positron emission tomography–computed tomography (PET–CT) and who had undergone a primary laparoscopic PAL.
Results.
From November 2007 to June 2010, 98 patients with LACC underwent pretherapeutic PAL. Two patients did not undergo PAL: extensive carcinomatosis was discovered in one case and a technical problem arose in the other. No perioperative complications occurred. Seven patients had a lymphocyst requiring an imaging-guided (or laparoscopic) puncture. Eight patients (8.4%, which corresponds to the false-negative PET–CT rate) had metastatic disease within PA lymph nodes. In cases of suspicious pelvic nodes on PET–CT, the risk for PA nodal disease was greater (24.0% versus 2.9%). When patients with and without surgical morbidity were compared, the median delay to the start of treatment was not significantly different (15 days; range, 3–49 days versus 18 days; range, 3–42 days).
Conclusions.
The morbidity of laparoscopic PAL was limited and the completion of treatment was not delayed when complications occurred. Nevertheless, if PET–CT of the pelvic area is negative, the interest in staging PAL could be discussed because the risk for PA nodal disease is very low.
doi:10.1634/theoncologist.2011-0007
PMCID: PMC3228132  PMID: 21659610
Cervical cancer; Para-aortic lymphadenectomy; Laparoscopy; Staging; Morbidity; Lymphocyst
6.  Low-Dose-Rate Definitive Brachytherapy for High-Grade Vaginal Intraepithelial Neoplasia 
The Oncologist  2011;16(2):182-188.
The efficacy and safety results of treatment with low-dose-rate vaginal brachytherapy for grade 3 vaginal intraepithelial neoplasia over a 25-year period at Gustave Roussy Institute are presented. This treatment was found to be both safe and effective.
Learning Objectives
After completing this course, the reader will be able to: Utilize data supporting the efficacy of low-dose definitive brachytherapy to inform clinical decisions about treating women with high-grade vaginal intraepithelial neoplasia.Implement methods for delivering low-dose definitive brachytherapy that minimize toxicity.Communicate to patients the type and incidence of toxic events associated with low-dose definitive brachytherapy.
This article is available for continuing medical education credit at CME.TheOncologist.com
Background.
Treatment of high-grade vaginal intraepithelial neoplasia (VAIN) is controversial and could include surgical excision, topical medication, brachytherapy, or other treatments. We report the results of low-dose-rate (LDR) vaginal brachytherapy for grade 3 VAIN (VAIN-3) over a 25-year period at Gustave Roussy Institute.
Patients and Methods.
We retrospectively reviewed the files of all patients treated at Gustave Roussy Institute for VAIN-3 since 1985. The treatment consisted of LDR brachytherapy using a personalized vaginal mold and delivered 60 Gy to 5 mm below the vaginal mucosa. All patients had at least an annual gynecological examination, including a vaginal smear.
Results.
Twenty-eight patients were eligible. The median follow-up was 41 months. Seven patients had a follow-up <2 years, and the median follow-up for the remaining 21 patients was 79 months. The median age at brachytherapy was 63 years (range, 38–80 years). Twenty-six patients had a history of VAIN recurring after cervical intraepithelial neoplasia and 24 had a previous hysterectomy. The median brachytherapy duration was 4.5 days. Median doses to the International Commission of Radiation Units and Measurements rectum and bladder points were 68 Gy and 45 Gy, respectively. The median prescription volume (60 Gy) was 74 cm3. Only one “in field” recurrence occurred, corresponding to a 5- and 10-year local control rate of 93% (95% confidence interval, 70%–99%). The treatment was well tolerated, with no grade 3 or 4 late toxicity and only one grade 2 digestive toxicity. No second cancers were reported.
Conclusion.
LDR brachytherapy is an effective and safe treatment for vaginal intraepithelial neoplasia.
doi:10.1634/theoncologist.2010-0326
PMCID: PMC3228085  PMID: 21262875
Vaginal neoplasms; Carcinoma in situ; Cervical intraepithelial neoplasia; Brachytherapy
7.  Prognosis and Prognostic Factors of the Micropapillary Pattern in Patients Treated for Stage II and III Serous Borderline Tumors of the Ovary 
The Oncologist  2011;16(2):189-196.
In this study on 168 patients with stage II and stage III serous borderline tumor of the ovary, micropapillary pattern did not appear to signify a poor prognosis. The only prognostic factor for recurrence in these patients was the use of conservative surgery.
Learning Objectives
After completing this course, the reader will be able to: Discuss the prognostic impact of a micropapillary pattern in patients with stage II and III serous borderline ovarian tumors (SBOT).Consider when conservative surgery is an appropriate intervention in patients with SBOT-MP.
This article is available for continuing medical education credit at CME.TheOncologist.com
Background.
To determine the prognosis of a micropapillary (MP) pattern in patients with stage II and stage III serous borderline tumor of the ovary (SBOT).
Methods.
Review of patients with stage II and stage III SBOT treated or referred to our institution with characterization of an MP pattern and its clinical impact.
Results.
In 1969–2006, 168 patients were reviewed. Fifty-six patients had SBOT-MP. The rate of conservative surgery was lower in the SBOT-MP group than in the typical SBOT group, but the rate of patients with more than three peritoneal sites with implants was higher in the SBOT-MP group. The rate of invasive implants was not statistically different between the two groups. Eighteen recurrences were observed (six of them in the form of invasive disease) in the SBOT-MP group. Only one death was observed. The overall survival times and recurrence-free intervals were similar in both groups. The only prognostic factor for recurrence in the SBOT-MP group was the use of conservative surgery.
Conclusions.
In the present series, an MP pattern doesn't appear to signify a poor prognosis. The only prognostic factor for recurrence in SBOT-MP was the use of conservative surgery. Further studies on the MP pattern are needed to evaluate prognosis and the results of conservative surgery.
doi:10.1634/theoncologist.2009-0139
PMCID: PMC3228092  PMID: 21273510
Borderline tumor; Conservative surgery; Micropapillary pattern; Ovary; Peritoneal implants; Recurrence
8.  Prognostic Factors and Morbidities After Completion Surgery in Patients Undergoing Initial Chemoradiation Therapy for Locally Advanced Cervical Cancer 
The Oncologist  2010;15(4):405-415.
The study evaluates the prognostic factors and morbidities of patients undergoing completion surgery for locally advanced-stage cervical cancer after initial chemoradiation therapy.
Learning Objectives
After completing this course, the reader will be able to: Rate the prognostic factors for overall survival in patients undergoing completion surgery after initial chemoradiation therapy (CRT) for locally advanced cervical cancer.In cervical cancer patients undergoing completion surgery, consider using laparoscopy to decrease the morbidity of the surgery.In cervical cancer patients undergoing completion surgery, use PET-CT imaging to improve detection of para-aortic involvement.
This article is available for continuing medical education credit at CME.TheOncologist.com
Purpose.
The aim of this study was to evaluate the prognostic factors and morbidities of patients undergoing completion surgery for locally advanced-stage cervical cancer after initial chemoradiation therapy (CRT).
Patients and Methods.
Patients fulfilling the following inclusion criteria were studied: stage IB2–IVA cervical carcinoma, tumor initially confined to the pelvic cavity on conventional imaging, pelvic external radiation therapy with delivery of 45 Gy to the pelvic cavity and concomitant chemotherapy (cisplatin, 40 mg/m2 per week) followed by uterovaginal brachytherapy, and completion surgery after the end of radiation therapy including at least a hysterectomy.
Results.
One-hundred fifty patients treated in 1998–2007 fulfilled the inclusion criteria. Prognostic factors for overall survival in the multivariate analysis were the presence and level of nodal spread (positive pelvic nodes alone: hazard ratio [HR], 2.03; positive para-aortic nodes: HR, 5.46; p < .001) and the presence and size of residual disease (RD) in the cervix (p = .02). Thirty-seven (25%) patients had 55 postoperative complications. The risk for complications was higher with a radical hysterectomy (p = .04) and the presence of cervical RD (p = .01).
Conclusion.
In this series, the presence and size of RD and histologic nodal involvement were the strongest prognostic factors. Such results suggest that the survival of patients treated using CRT for locally advanced cervical cancer could potentially be enhanced by improving the rate of complete response in the irradiated area (cervix or pelvic nodes) and by initially detecting patients with para-aortic spread so that treatment could be adapted in such patients. The morbidity of completion surgery is high in this context.
doi:10.1634/theoncologist.2009-0295
PMCID: PMC3227965  PMID: 20332143
Chemoradiation therapy; Completion surgery; Locally advanced cervical cancer; Morbidities; Nodal involvement; Prognostic factors; Residual disease; Survival
9.  Early stage (IA-IB) primary carcinoma of the fallopian tube: case-control comparison to adenocarcinoma of the ovary 
Objective
Early stage primary carcinoma of the fallopian tube (PCFT) is an uncommon condition when strict criteria are applied. The aim of this study was to compare the outcome stage IA-IB PCFT to a matched group of ovarian cancer (OC).
Methods
Between 1990 and 2008, 32 patients with stage IA-IB of PCFT were recorded in the database of three French Institutions. A control group of patients with OC was constituted.
Results
Eleven eligible PCFT cases and 29 OC controls fulfilled the stringent inclusion criteria. Median follow-up was 70.2 months. Five-year overall survival was 83.3% (95% confidence interval [CI], 27.3 to 97.5) for PCFT and 88.0% (95% CI, 66.9 to 96.0) for OC (p=0.93). In the subgroup of patients with grade 2-3, the outcome was similar in PCFT compared to OC patients (p=0.75). Five-year relapse-free survival was respectively 62.5% (95% CI, 22.9 to 86.1) and 85.0% (95% CI, 64.6 to 94.2) in the PCFT and OC groups (p=0.07). In the subgroup of patients (grade 2-3), there was no difference between PCFT and OC (p=0.65).
Conclusion
The findings did not reveal any difference in prognosis between early stage of PCFT and OC when grade is taken into account. Management of PCFT should mirror that of ovarian carcinoma.
doi:10.3802/jgo.2011.22.1.9
PMCID: PMC3097339  PMID: 21607090
Fallopian tube carcinoma; Ovarian cancer; Early stage; Case-control study

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