[Stage IB2, IIA and IIB cervical carcinoma without lymph node extension treated with neoadjuvant chemoradiotherapy]. / Cancers du col utérin de stade IB2, IIA et IIB sans extension ganglionnaire traités par chimioradiothérapie préopératoire.

PURPOSE: To evaluate the results of preoperative chemoradiation for resectable bulky cervical carcinoma without lymph node involvement after surgical lymph node staging. PATIENTS AND METHODS: Between 2000 and 2010, 45 patients with cervical carcinoma stage IB2 (11 patients), IIA2 (3 patients) and IIB with proximal parametrial invasion (31 patients) were treated with pelvic radiation therapy at a dose of 40.5Gy and concurrent platin (44 patients) or mitomycin (one patient). Forty-two patients had low-dose-rate preoperative uterovaginal brachytherapy at a dose of 20Gy. All patients underwent hysterectomy. Three patients had postoperative low-dose-rate vaginal brachytherapy at a dose of 20Gy. The median follow-up was 34 months. RESULTS: A pathologic cervical residual tumor was observed in 16 patients (35.6%). Six patients presented a relapse (13.3%) with a median delay of 8 months. The 5-year overall survival and disease free survival rates were 88.4% and 84.7%, respectively. In univariable analysis, a cervical residual tumor was the only predictive factor of overall survival (P=0.03). Late toxicity was observed in seven patients. CONCLUSION: Chemoradiation followed by surgery for resectable bulky stage I-II cervical carcinoma without lymph node involvement on pretreatment surgical staging can be used with a good local control and a high rate of 5-year overall survival.

Physicians' Attitudes Towards the Advice of a Guideline-Based Decision Support System: A Case Study With OncoDoc2 in the Management of Breast Cancer Patients.

When wrongly used, guideline-based clinical decision support systems (CDSSs) may generate inappropriate propositions that do not match the recommendations provided by clinical practice guidelines (CPGs). The user may decide to comply with or react to the CDSS, and her decision may finally comply or not with CPGs. OncoDoc2 is a guideline-based CDSS for breast cancer management. We collected 394 decisions made by multidisciplinary meeting physicians in three hospitals where the CDSS was evaluated. We observed a global CPG compliance of 86.8% and a global CDSS compliance of 75.4%. Non-CPG compliance was observed in case of a negative reactance to the CDSS, when users did not follow a correct CDSS proposition (8.6% of decisions). Because of errors in patient data entry, OncoDoc2 delivered non-recommended propositions in 21.3% of decisions, leading to compliances with CDSS and CPGs of respectively 21.4% and 65.5%, whereas both compliances exceeded 90% when CDSS advices included CPG recommendations. Automation bias, when users followed an incorrect CDSS proposition explained the remaining non-compliance with CPGs (4.6% of decisions). Securing the use of CDSSs is of major importance to warranty patient safety and benefit of their potential to improve care.

Health information technology: use it well, or don't! Findings from the use of a decision support system for breast cancer management.

The potential of health information technology is hampered by new types of errors which impact is not totally assessed. OncoDoc2 is a decision support system designed to support treatment decisions of multidisciplinary meetings (MDMs) for breast cancer patients. We evaluated how the way the system was used had an impact on MDM decision compliance with clinical practice guidelines. We distinguished "correct navigations" (N+), "incorrect navigations" (N-), and "missing navigations" (N0), according to the quality of data entry when using OncoDoc2. We collected 557 MDM decisions from three hospitals of Paris area (France) where OncoDoc2 was routinely used. We observed 33.9% N+, 36.8% N-, and 29.3% N0. The compliance rate was significantly different according to the quality of navigations, 94.2%, 80.0%, and 90.2% for N+, N-, and N0 respectively. Surprinsingly, it was better not to use the system (N0) than to use it improperly (N-).

Which patients may benefit from the use of a decision support system to improve compliance of physician decisions with clinical practice guidelines: a case study with breast cancer involving data mining.

OncoDoc2 is a guideline-based clinical decision support system (CDSS) for breast cancer management. It has been used as an intervention in a randomized controlled trial carried out to evaluate the impact of using a CDSS upon the compliance with clinical practice guidelines (CPGs) of multidisciplinary staff meeting decisions. Data mining was used to discover multi-criteria regularities as "emerging patterns" (EPs) associated with compliance and non-compliance with CPGs when using and not using OncoDoc2 and to assess which patients may benefit from the use of the CDSS. Decision data was collected from all participating centers. The number of EPs associated with non-compliance is smaller in the intervention arm, which suggests a practice harmonization effect of OncoDoc2. EPs associated with compliant decisions in both arms of the trial correspond to situations well identified in CPGs. EPs associated with non-compliant decisions when the system is not used are associated with compliance when the system is used except in clinical situations where evidence is lacking.

Accuracy of clinical data entry when using a computerized decision support system: a case study with OncoDoc2.

Some studies suggest that the implementation of health information technology (HIT) introduces unpredicted and unintended consequences including e-iatrogenesis. OncoDoc2 is a guideline-based clinical decision support system (CDSS) applied to the management of breast cancer. The system is used by answering closed-ended questions in order to document patient data while navigating through the knowledge base until the best patient-specific recommended treatments are obtained. OncoDoc2 has been used by three hospitals in real clinical settings and for genuine patients. We analysed 394 navigations, recorded on a 10-month period, which correspond to 6,025 data entries. The data entry error rate is 4.2%, spread over 52% of incorrect navigations (N-). However, the overall compliance rate of clinical decisions with guidelines significantly increased from 72.8% (without CDSS) to 87.3% (with CDSS). Although this increase is lowered because of N- navigations (compliance rates are respectively 95% and 80% for N+ and N- navigations), the benefits of HIT outweighted its disadvantages in our study.

Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review.

Clinicians can use biomarkers to guide therapeutic decisions in estrogen receptor positive (ER+) breast cancer. One such biomarker is cellular proliferation as evaluated by Ki-67. This biomarker has been extensively studied and is easily assayed by histopathologists but it is not currently accepted as a standard. This review focuses on its prognostic and predictive value, and on methodological considerations for its measurement and the cut-points used for treatment decision. Data describing study design, patients' characteristics, methods used and results were extracted from papers published between January 1990 and July 2010. In addition, the studies were assessed using the REMARK tool. Ki-67 is an independent prognostic factor for disease-free survival (HR 1.05-1.72) in multivariate analyses studies using samples from randomized clinical trials with secondary central analysis of the biomarker. The level of evidence (LOE) was judged to be I-B with the recently revised definition of Simon. However, standardization of the techniques and scoring methods are needed for the integration of this biomarker in everyday practice. Ki-67 was not found to be predictive for long-term follow-up after chemotherapy. Nevertheless, high KI-67 was found to be associated with immediate pathological complete response in the neoadjuvant setting, with an LOE of II-B. The REMARK score improved over time (with a range of 6-13/20 vs. 10-18/20, before and after 2005, respectively). KI-67 could be considered as a prognostic biomarker for therapeutic decision. It is assessed with a simple assay that could be standardized. However, international guidelines are needed for routine clinical use.

Breast cancer affects both the hippocampus volume and the episodic autobiographical memory retrieval.

BACKGROUND: Neuroimaging studies show the hippocampus is a crucial node in the neural network supporting episodic autobiographical memory retrieval. Stress-related psychiatric disorders, namely Major Depression and Post Traumatic Stress Disorder (PTSD), are related to reduced hippocampus volume. However, this is not the case for remitted breast cancer patients with co-morbid stress-related psychiatric disorders. This exception may be due to the fact that, consequently to the cancer experience as such, this population might already be characterized by a reduced hippocampus with an episodic autobiographical memory deficit. METHODOLOGY: We scanned, with a 3T Siemens TRIO, 16 patients who had lived through a "standard experience of breast cancer" (breast cancer and a standard treatment in remission since 18 month) in the absence of any associated stress-related psychiatric or neurological disorder and 21 matched controls. We then assessed their episodic autobiographical memory retrieval ability. PRINCIPAL FINDINGS: Remitted breast cancer patients had both a significantly smaller hippocampus and a significant deficit in episodic autobiographical memory retrieval. The hippocampus atrophy was characterized by a smaller posterior hippocampus. The posterior hippocampus volume was intimately related to the ability to retrieve negative memories and to the past experience of breast cancer or not. CONCLUSIONS/SIGNIFICANCE: These results provide two main findings: (1) we identify a new population with a specific reduction in posterior hippocampus volume that is independent of any psychiatric or neurological pathology; (2) we show the intimate relation of the posterior hippocampus to the ability to retrieve episodic autobiographical memories. These are significant findings as it is the first demonstration that indicates considerable long-term effects of living through the experience of breast cancer and shows very specific hippocampal atrophy with a functional deficit without any presence of psychiatric pathology.

Influence of geriatric consultation with comprehensive geriatric assessment on final therapeutic decision in elderly cancer patients.

Elderly patients represent a heterogeneous population in which decisions on cancer treatment are often difficult. The present study aims to report a 2-year period of the activity of geriatric assessment consultations and the impact on treatment decisions. Since January 2007, we have systematically carried out geriatric consultations, using well-known international scales, for elderly patients in whom treatment decisions appear complex to oncologists. From January 2007 to November 2008, 161 patients (57 men, 104 women; median age 82.4 years, range 73-97) were seen at geriatric consultations. Most of the patients (134/161) were undergoing first-line treatment and cancer was metastatic in 86 patients (53%). Geriatric assessment found severe comorbidities (grade 3 or 4 in CIRS-G scale) in 75 patients, dependence for at least one activity of daily living (ADL) in 52 patients, cognitive impairment in 42 patients, malnutrition in 104 patients (65%) and depression in 39 patients. According to the oncologists' prior decisions, there were no changes in treatment decisions in only 29 patients. Cancer treatment was changed in 79 patients (49%), including delayed therapy in 5 patients, less intensive therapy in 29 patients and more intensive therapy in 45 patients. Patients for whom the final decision was delayed or who underwent less intensive therapy had significantly more frequent severe comorbidities (23/34, p<0.01) and dependence for at least one ADL (19/34, p<0.01). In this study, we have found that comprehensive geriatric evaluation did significantly influence treatment decisions in 82% of our older cancer patients.

[Clinical practice guidelines 2008 for the surgical treatment, medical first-line and consolidation treatments of patients with epithelial ovarian cancer--update. According to the methodology of Standards, Options: Recommendations (SOR)]. / Recommandations pour la pratique clinique 2008 pour le traitement chirurgical, les traitements médicaux complémentaires et de consolidation des patientes atteintes de tumeurs épithéliales malignes de l'ovaire--mise à jour. Selon la méthodologie des Standards, Options: Recommandations (SOR).

CONTEXT: Ovarian cancers represent the 4th cause of mortality by cancer for women in France and were responsible of more than 3,000 deaths in 2005. The Standards, Options: Recommendations (SOR) project has been undertaken by the French National Federation of Cancers Centers is now part of the French National Cancer Institute since the 1st of may 2008. The project involves the development and updating of evidence-based clinical practice guidelines (CPG) in oncology. Following the monitoring process, we identified new data conferring sufficient elements to justify an updating of the CPG concerning the surgical, the medical fi rst-line and consolidation treatments of epithelial ovarian cancers. OBJECTIVES: To update the CPG according to the methodology SOR.

Preoperative concurrent radiation therapy and chemotherapy for bulky stage IB2, IIA, and IIB carcinoma of the uterine cervix with proximal parametrial invasion.

PURPOSE: To evaluate toxicity, local tumor control, and survival after preoperative chemoradiation for operable bulky cervical carcinoma. METHODS AND MATERIALS: Between December 1991 and July 2006, 92 patients with operable bulky stage IB2, IIA, and IIB cervical carcinoma without pelvic or para-aortic nodes on pretreatment imaging were treated. Treatment consisted of preoperative external beam pelvic radiation therapy (EBRT) and concomitant chemotherapy (CT) during the first and fourth weeks of radiation combining 5-fluorouracil and cisplatin. The pelvic radiation dose was 40.5 Gy over 4.5 weeks. EBRT was followed by low-dose rate uterovaginal brachytherapy with a total dose of 20 Gy in 62 patients. After a median rest period of 44 days, all patients underwent Class II modified radical hysterectomy with bilateral pelvic lymphadenectomy. Thirty patients who had not received preoperative uterovaginal brachytherapy underwent postoperative low-dose-rate vaginal brachytherapy at a dose of 20 Gy. The mean follow-up was 46 months. RESULTS: Pathologic residual tumor was observed in 43 patients. After multivariate analysis, additional preoperative uterovaginal brachytherapy was the single significant predictive factor for pathologic complete response rate (p = 0.019). The 2- and 5-year disease-free survival (DFS) rates were 80.4% and 72.2%, respectively. Pathologic residual cervical tumor was the single independent factor decreasing the probability of DFS (p = 0.020). Acute toxicities were moderate. Two severe ureteral complications requiring surgical intervention were observed. CONCLUSIONS: Concomitant chemoradiation followed by surgery for operable bulky stage I-II cervical carcinoma without clinical lymph node involvement can be used with acceptable toxicity. Pathologic complete response increases the probability of DFS.

[Local recurrence after breast conserving treatment: place of surgery]. / Récidives locales après traitement conservateur des cancers du sein: place de la chirurgie.

Since the end of the sixties, conservative radiosurgical treatment is the standard for unifocal breast cancers < 3 cm. Retrospective and randomised trials confirmed identical survival, but an increased second failure's rate. Impact of this local failure on survival is controversy. Different prognostic factors were identified by the authors. Local extension of the local failure and inflammatory signs, the delay of its apparition and its site (witch could difference true local failure and new tumour) the histologic type of the local failure, the phase S cells rate, the N status, and characteristics of the initial tumour such as the N status, the tumour's size. The surgical treatment of the local failure is classically the salvage mastectomy associated with immediate breast reconstruction, often by cutaneous-muscular flaps. A second conservative treatment could eventually be proposed only if breast size and radiotherapy sequels would permit a second carcinologic and cosmetic surgical treatment: wide local excision and re-irradiation, unifocal tumour < 1 cm preferentially intraductal, well differentiated without lymphovascular embole, without extensive intraductal, second new cancer (in other quadrant than the initial tumor after a long enough delay), efficient and long time survey. RMN with identification of the prognostic criteria would contribute to identify the local failure witch could benefit of an iterative conservative treatment.

[Clinical practice guidelines: Standards, Options and Recommendations for first line medical treatment of patients with ovarian neoplasms (summary report)]. / Recommandations pour la pratique clinique Standards, Options et Recommandations 2003 pour le traitement médical de première ligne des patientes atteintes de tumeurs épithéliales malignes de l'ovaire, mise à jour (rapport abrégé).

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the French Federation of Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVE: To update clinical practice guidelines for first line medical treatment of patients with ovarian neoplasms in collaboration with the French Society for Gynaecologica Oncology. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts. The CPGs are defined following the definitions of the Standards, Options and Recommendations project. Once the guideline has been developed, the document is submitted for review by independent reviewers. RESULTS: This article is a summary version of the full document presenting the clinical practice guidelines with algorithms. After surgery, most patients with ovarian neoplasms need adjuvant medical treatment. These guidelines concern the initial medical treatment (chemotherapy, hormone treatment and immunotherapy) and potential consolidation treatment. To complete the indications, two alternative treatment strategies are taken into account: no treatment and radiotherapy. This updated version concerns the indications and the modalities of chemotherapy. The main modifications are: 1) first-line chemotherapy for ovarian neoplasm can be taxane-platinum or carboplatine alone; 2) poly-chemotherapy is no longer a standard; 3) for early stages, except for stage IA grade I non-clear-cell tumours, adjuvant chemotherapy should be preferred to no treatment; 4) chemotherapy is standard for all stage III tumours, irrespective of the surgical result; 5) for stage IA G2-3 to IIA tumours, complete surgical staging and determination of the histological grade are standards.

Combined chemotherapy and preoperative irradiation for locally advanced noninflammatory breast cancer: updated results in a series of 120 patients.

PURPOSE: To evaluate our updated data concerning survival and locoregional control in a prospective study of locally advanced noninflammatory breast cancer (LABC) after primary chemotherapy (CT) followed by external preoperative irradiation (RT). METHODS AND MATERIALS: Between 1982 and 1998, 120 patients (75 Stage IIIA, 41 Stage IIIB, and 4 Stage IIIC according to AJCC staging system 2002) were treated by four courses of induction CT with anthracycline-containing combinations followed by preoperative RT (45 Gy to the breast and nodal areas) and a fifth course of CT. Three different locoregional approaches were proposed depending on tumor characteristics and tumor response. After completion of local therapy, all patients received a sixth course of CT and a maintenance adjuvant CT regimen without anthracycline. The median follow-up from the beginning of treatment was 140 months. RESULTS: Mastectomy and axillary dissection were performed in 49 patients (with residual tumor larger than 3 cm in diameter or located behind the nipple or with bifocal tumor), and conservative treatment in 71 patients (39 achieved clinical complete response or partial response >90% and received additional radiation boost to initial tumor bed; 32 had residual mass < or =3 cm in diameter and were treated by wide excision and axillary dissection followed by a boost to the excision site). Ten-year actuarial local failure rate was 13% after RT alone, 23% after wide excision and RT, and 4% after mastectomy (p = 0.1). After multivariate analysis, possibility of breast-conserving therapy was related to initial tumor size (<6 cm vs. > or =6 cm in diameter, p = 0.002). Ten-year overall metastatic disease-free survival rate was 61%. After multivariate analysis, metastatic disease-free survival rates were significantly influenced by clinical stage (Stage IIIA-B vs. IIIC, p = 0.0003), N-stage (N0 vs. N1-2a, and 3c, p = 0.017), initial tumor size (<6 cm vs. > or =6 cm in diameter, p = 0.008), and tumor response after induction CT and preoperative RT (clinically complete response + partial response vs. nonresponder, p = 0.0015). In the nonconservative breast treatment group, of the 32 patients with no change in clinical tumor size after induction CT, the 10-year metastatic disease-free survival rate was 59% with only one local relapse. Arm lymphedema was noted in 17% (14 of 81) after axillary dissection and in 2.5% (1 of 39) without axillary dissection. Cosmetic results were satisfactory in 70% of patients treated by RT alone and in 51.5% of patients after wide excision and RT. CONCLUSION: Despite the poor prognosis of patients with LABC resistant to primary anthracycline-based regimen, aggressive locoregional management using preoperative RT and mastectomy with axillary dissection offers a possibility of long-term survival with low local failure rate for patients without extensive nodal disease. On the other hand, the rate of local failure seems to be high in patients with clinical partial tumor response after induction CT and breast-conserving treatment combining preoperative RT and large wide excision.

[Identification and management of hereditary predisposition to cancer of the breast and the ovary (update 2004)]. / Identification et prise en charge des prédispositions héréditaires aux cancers du sein et de l'ovaire (mise à jour 2004).

BACKGROUND: Since the last recommendations, up to 2,500 new references had been published on that topic. METHODOLOGY: On the behalf of the health Minister, the Ad Hoc Committee consisted of 13 experts carried out a first version revisited by five additional experts who critically analyzed the first version of the report. MAIN UPDATING: Breast and ovarian cancer seem to be associated with fewer deleterious mutation of BRCA12 and BRCA2 than previously thought. The screening of ovarian cancer is still not an attractive option while in contrast MRI may be soon for these young women with dense breast, the recommended option for breast cancer screening. The effectiveness of prophylactic surgeries is now well established. French position is to favor such surgeries with regard to a quality of life in line with the expected benefit, and providing precise and standardized process described in the recommendation. CONCLUSIONS: Due to methodological flaws, the low power and a short follow-up of the surveys, this statement cannot however aspire to a high stability.

Operable Stages IB and II cervical carcinomas: a retrospective study comparing preoperative uterovaginal brachytherapy and postoperative radiotherapy.

PURPOSE: To evaluate our data concerning prognostic factors and treatment toxicity in a series of operable cervical carcinomas. METHODS AND MATERIALS: Between May 1972 and January 1994, 414 patients with cervical carcinoma, staged according to the 1995 FIGO staging system (286 Stage IB1, 38 Stage IB2, 56 Stage IIA, and 34 Stage IIB with 1/3 proximal parametrial involvement), underwent radical hysterectomy with (n = 380) or without (n = 34) bilateral pelvic lymph node dissection (N+: n = 68). Group I included 168 patients who received postoperative radiation therapy (RT): 64 patients had low-dose-rate vaginal brachytherapy with a median total dose (MTD) of 50 Gy; 93 patients had external beam pelvic RT (EBPRT) with an MTD of 45 Gy over 5 weeks, followed by low-dose-rate vaginal brachytherapy (MTD: 20 Gy); and 11 patients had EBPRT alone (MTD: 50 Gy over 6 weeks). Group II included 246 patients treated with preoperative low-dose-rate uterovaginal brachytherapy (MTD: 65 Gy); 32 of these 246 patients also received postoperative EBPRT (MTD: 45 Gy over 5 weeks) delivered to the parametria and pelvic nodes. Mean follow-up from the beginning of treatment was 106 months. RESULTS: First events included isolated locoregional recurrences (35 patients), isolated distant metastases (27 patients), and locoregional recurrences with synchronous metastases (13 patients). The 10-year disease-free survival (DFS) rate was 88% for Stage IB1, 44% for Stage IB2, 65% for Stage IIA, and 48% for Stage IIB. Multivariate analysis showed that independent factors influencing the probability of DFS were as follows: cervical site (exocervical or endocervical vs. both endo- and exocervical, relative risk [RR]: 1.77, p = 0.047), vascular space invasion (no vs. yes, RR: 1.95, p = 0.041), age (>51 years vs. 1 cm: 83% vs. 41%, respectively, p = 0.001). The overall postoperative complication rate was 10% in Group I and 9% in Group II (p = 0.7). The rate of postoperative ureteral complications requiring surgical intervention was lower in Group I than in Group II (0.6% vs. 2.3%, respectively, p = 0.03). The overall 10-year rate for Grade 3 and 4 late radiation complications was 10.4%. Postoperative EBPRT significantly increased the 10-year rate for Grade 3 and 4 late radiation complications (yes vs. no: 22% vs. 7%, respectively, p = 0.0002). CONCLUSION: The prognosis for patients with cervical carcinoma was not influenced by the sequence of adjuvant RT (preoperative uterovaginal brachytherapy vs. postoperative RT) for Stages IB, IIA, and IIB with 1/3 proximal parametrial involvement. However, postoperative EBPRT increased the risk of late radiation complications.

Longterm followup of posthysterectomy vaginal vault prolapse abdominal repair: a report of 85 cases.

BACKGROUND: There are many surgical procedures to treat posthysterectomy vaginal vault prolapse. Abdominal sacral colpopexy is one of these procedures. The aim of this study was to review the cases of 85 consecutive patients treated by this technique since 1978 by the same surgical team using the same procedure. Our surgical procedure will be explained. STUDY DESIGN: Eighty-five patients were treated in our department between 1978 and 1998 for posthysterectomy vaginal vault prolapse. The mean age was 55.42 years. The mean weight was 63.37 kg. Their parity ranged from 0 to 5 (mean, 2.54). The interval of time between hysterectomy and vaginal vault prolapse repair ranged from 1 to 37 years (mean, 17.92 years). The main indication for hysterectomy was uterine leiomyomas. Of these patients, 67.05% had stress urinary incontinence, and mean urethral closure pressure was 48.7 cm H2O. All patients had abdominal sacral colpopexy associated with a Burch procedure and a posterior perineal repair. RESULTS: Seventeen patients had postoperative fever. Twenty-two had urinary tract infections. Two patients had to undergo blood transfusion. Three patients had postoperative urinary retention. The median longterm followup was 10.5 years; 27.05% of patients had relapsing stress urinary incontinence. Two patients had a relapse of the vaginal vault prolapse. CONCLUSIONS: The abdominal sacral colpopexy is a safe operation with low morbidity and long-standing good results. It can be recommended for sexually active women. Nevertheless, the Burch procedure performed with this operation failed to prevent recurrence of urinary incontinence.