Neoadjuvant chemotherapy for advanced stage cervical cancer in a pregnant patient: report of one case with rapid tumor progression.
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Adult↗
Biomedical subjects
Christine Haie-Meder
Publications and source records attributed to Christine Haie-Meder.
[Medical treatment of metastatic or recurrent cancer of the cervix].
Cervical cancer is the most frequent gynaecological cancer worldwide. Incidence is decreasing in industrialized countries but remains high in poorest countries. In metastatic or recurrent disease, the treatment is more often palliative. Chemotherapy yields some efficiency in non-irradiated fields but the benefit should be balanced with the treatment toxicities. In this setting, cisplatin is considered as the drug of reference, but responses rates are poor. So far, combined chemotherapy has not been shown better than cisplatin alone. Recently, results for cisplatin associated with topotecan appear to be promising while used for treatment in metastatic or recurrent disease. However, the bad prognosis of this illness leads to keep on looking for better treatments. Targeted therapeutics and immunotherapy against human papilloma virus could bear significant progress for treatment of cervical cancer.
Adult↗
Intercomparison of treatment concepts for MR image assisted brachytherapy of cervical carcinoma based on GYN GEC-ESTRO recommendations.
PURPOSE: To perform a multicentre intercomparison study of treatment concepts for MRI assisted brachytherapy of cervix cancer based on recommendations of the Gynaecological GEC-ESTRO Working Group. METHODS: Each participating centre (IGR Paris, University Hospital Leuven, Medical University of Vienna) contributed data of one patient with comparable clinical features. GTV, High Risk CTV (HR CTV), Intermediate Risk CTV (IR CTV) and organ walls of bladder, rectum and sigmoid colon were delineated at the time of each brachytherapy fraction on axial MR images with the applicator in place. Dose-volume histograms were calculated to evaluate doses to tumour, target volumes and organs at risk. Dose values were biologically normalised to equivalent doses in 2 Gy fractions (EQD(2), equivalent to 50 cGy/h low dose rate) applying the linear-quadratic model. RESULTS: Total doses to point A from external beam therapy plus brachytherapy ranged from 85 to 91 Gy and were close to the dose covering 90% of HR CTV (D90=85-87 Gy). D90 of IR CTV was within 69-73 Gy. Doses to organs at risk were comparable. CONCLUSIONS: This study indicates the feasibility of the GEC-ESTRO recommendations. Despite different treatment concepts, biologically normalised total doses to tumour, target volumes and organs at risk were comparable.
Brachytherapy↗
Recommendations from gynaecological (GYN) GEC ESTRO working group (II): concepts and terms in 3D image-based treatment planning in cervix cancer brachytherapy-3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics, radiobiology.
The second part of the GYN GEC ESTRO working group recommendations is focused on 3D dose-volume parameters for brachytherapy of cervical carcinoma. Methods and parameters have been developed and validated from dosimetric, imaging and clinical experience from different institutions (University of Vienna, IGR Paris, University of Leuven). Cumulative dose volume histograms (DVH) are recommended for evaluation of the complex dose heterogeneity. DVH parameters for GTV, HR CTV and IR CTV are the minimum dose delivered to 90 and 100% of the respective volume: D90, D100. The volume, which is enclosed by 150 or 200% of the prescribed dose (V150, V200), is recommended for overall assessment of high dose volumes. V100 is recommended for quality assessment only within a given treatment schedule. For Organs at Risk (OAR) the minimum dose in the most irradiated tissue volume is recommended for reporting: 0.1, 1, and 2 cm3; optional 5 and 10 cm3. Underlying assumptions are: full dose of external beam therapy in the volume of interest, identical location during fractionated brachytherapy, contiguous volumes and contouring of organ walls for >2 cm3. Dose values are reported as absorbed dose and also taking into account different dose rates. The linear-quadratic radiobiological model-equivalent dose (EQD2)-is applied for brachytherapy and is also used for calculating dose from external beam therapy. This formalism allows systematic assessment within one patient, one centre and comparison between different centres with analysis of dose volume relations for GTV, CTV, and OAR. Recommendations for the transition period from traditional to 3D image-based cervix cancer brachytherapy are formulated. Supplementary data (available in the electronic version of this paper) deals with aspects of 3D imaging, radiation physics, radiation biology, dose at reference points and dimensions and volumes for the GTV and CTV (adding to [Haie-Meder C, Pötter R, Van Limbergen E et al. Recommendations from Gynaecological (GYN) GEC ESTRO Working Group (I): concepts and terms in 3D image-based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV. Radiother Oncol 2005;74:235-245]). It is expected that the therapeutic ratio including target coverage and sparing of organs at risk can be significantly improved, if radiation dose is prescribed to a 3D image-based CTV taking into account dose volume constraints for OAR. However, prospective use of these recommendations in the clinical context is warranted, to further explore and develop the potential of 3D image-based cervix cancer brachytherapy.
Brachytherapy↗
Functional outcome of patients with benign meningioma treated by 3D conformal irradiation with a combination of photons and protons.
PURPOSE: To evaluate efficacy and tolerance of external fractionated combination of photon and proton radiation therapy (RT) for intracranial benign meningiomas. METHODS AND MATERIALS: Between 1994 and 2002, 51 patients with intracranial meningiomas of the base of the skull were treated with a combination of photon and proton RT. Median total dose was 60.6 cobalt Gy equivalent (54-64). One hundred eight eye-related symptoms were collected; 80 other symptoms were noted and followed up. RESULTS: Mean follow-up was 25.4 months. Acute tolerance was excellent. Out of the 108 eye-related symptoms, 106 (96%) were evaluated. Improvements were reported for 73 (68.8%) of them. Out of the 88 other miscellaneous symptoms, 81 (92%) were evaluated. Improvements were reported in 54 cases (67%). Median time to improvement ranged from 1 to 24 months after completion of the radiotherapy, depending on the symptom. We did not observe any worsening of primary clinical signs. Radiologically, 1 patient relapsed 4 months after the end of irradiation. Pathology revealed a malignant (Grade 3) transformation of the initial Grade 1 meningioma. Four-year local control and overall survival rates were, respectively, 98% and 100%. Stabilization of the tumor was observed in 38 cases (72%), volume reduction in 10 cases (20%), and intratumor necrosis in 3 cases. Two patients complained of Grade 3 side effects: 1 unilateral hearing loss requiring aid and 1 case of complete pituitary deficiency. CONCLUSION: These results stressed the clinical efficacy of fractionated-associated photon-proton RT in the treatment of meningiomas, especially on cranial nerve palsies, without severe toxicity in almost all patients.
Adolescent↗
Recommendations for image-based intracavitary brachytherapy of cervix cancer: the GYN GEC ESTRO Working Group point of view: in regard to Nag et al. (Int J Radiat Oncol Biol Phys 2004;60:1160-1172).
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Brachytherapy↗
Results of hysterectomy in patients with bulky residual disease at the end of chemoradiotherapy for stage IB2/II cervical carcinoma.
BACKGROUND: We assessed the clinical outcome after hysterectomy in patients with bulky residual disease after chemoradiotherapy for stage IB2/II cervical carcinoma. METHODS: Subjects were 10 patients who had bulky (>2 cm) residual disease in the cervix after external radiotherapy (45 Gy) combined with concomitant chemotherapy (cisplatin 40 mg/m2/week) and uterovaginal brachytherapy (15 Gy). RESULTS: Extrafascial hysterectomy was performed in three patients, type II radical hysterectomy was performed in six patients, and pelvic exenteration was performed in one patient. Pelvic lymphadenectomy was performed in eight patients, and para-aortic lymphadenectomy was performed in eight. Five patients had nodal involvement (pelvic nodes in four and para-aortic nodes in four), and six had lymphovascular space involvement. Surgical margins were free in nine patients. Seven patients developed grade 2 (n = 3) and/or grade 3 (n = 4) complications. The median duration of follow-up after surgery was 22 months (range, 1-37 months). With follow-up available in nine patients, seven relapsed, and only two remained disease free. CONCLUSIONS: This series confirms the high rate of nodal spread in patients with bulky residual cervical disease after chemoradiotherapy. Furthermore, patients who underwent hysterectomy had a high complication rate. Only two patients are alive and disease free. The results of surgery are disappointing; surgery does not seem to improve the survival of these patients.
Adult↗
Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group (I): concepts and terms in 3D image based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV.
BACKGROUND AND PURPOSE: Brachytherapy (BT) plays a crucial role in the management of invasive cervix cancer from stage I to IV. Intracavitary techniques are based on afterloading devices, with different types of applicators. CT and/or MRI compatible applicators allow a sectional image based approach with a better assessment of gross tumour volume (GTV) and definition and delineation of target volume (CTV) compared to traditional approaches. Accurate and reproducible delineation of GTV, CTV and PTV, as well as of critical organs has a direct impact on BT treatment planning, especially if it is possible to adapt the pear-shape isodose by optimisation using DVH analysis. When introducing a 3D image based approach for GTV and CTV assessment, there is a need for a common language to describe the concepts and to define the terms which are to be used. METHODS: In 2000, GEC-ESTRO decided to support 3D imaging based 3D treatment planning approach in cervix cancer BT with the creation of a Working Group. The task was to describe basic concepts and terms and to work out a terminology enabling various groups working in this advanced field to use a common language. The recommendations described in this report were proposed based on clinical experience and dosimetric concepts of different institutions (IGR, Leuven, Vienna) and were stepwise validated against the background of different clinical experience. CONCLUSIONS: As GTV and CTV for BT change significantly during treatment, time frame for assessment of GTV and CTV for BT is specified in this report: at time of diagnosis GTV(D), CTV(D) and at time of BT GTV(B), CTV(B). Furthermore, CTV for BT is defined related to risk for recurrence: high risk CTV and intermediate risk CTV. Beside verbal descriptions detailed examples are given, partly in form of schematic drawings.
Brachytherapy↗
3D image based concepts in brachytherapy for cervical cancer.
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Brachytherapy↗
[Use of the functional imaging modalities in radiation therapy treatment planning in patients with glioblastoma].
Glioblastoma multiforme still remains, at present, the most frequent and deadly primary malignant glioma in adult. Despite safer and larger neurosurgical resections, patients almost always relapse very close or inside the tumor bed. Since more than 20 years, radiation therapy (RT) continue delivering the same dose of 60 Gy in 6 weeks, more precisely guided with CT-scanner and magnetic resonance imaging (MRI) in the treatment position. If morbidity has decreased with "non whole-brain" volumes, RT is nearly always failing locally, as surgery. Until now, all the series evaluating escalating doses (up to 80-90 Gy) in limited volumes have failed. One can really question : is the good dose delivered in the adequate volume? Main goal of new imaging techniques is to better visualize microscopic extension of malignant glioma cells. As based on metabolic principles, areas of abnormalities visualized with functional imaging have a different meaning, often complementary from conventional data. The four evaluated techniques are : magnetic resonance spectroscoy (MRS), functional MRI (fMRI), 18FDG or methionine PET, IMT (123iodine-alpha-methyl-thyrosine) SPECT. Each technique has potential interests and limits, MRS and fMRI appearing the most promising : they have both acceptable spatial resolution and can be executed just after conventional MRI acquisition. Areas of functional abnormalities are only partially including areas of hyperintensity in T1, T2 weighted MRI. It is therefore highly possible that, using it complementary to conventional CT and MRI for RT treatment planning, they add some precious informations; consequently, the very limited efficacy/toxicity ratio could be increased. This hypothesis will only be confirmed by prospective studies registering in parallel both functional and morphological abnormalities, linking them with sites of local recurrence. Once "targeted" the real microscopically invaded areas, one can speculate on new escalating dose studies, delivering RT in "adequate" volumes, combining it with new "targeted" drugs, as already recently demonstrated in head and neck cancers.
Brain Neoplasms↗
[Concomitant chemoradiation in patients with cervix cancer].
Cervical cancer is the 2nd most common cancer among women, behind breast cancer. Concomitant chemoradiation has been assessed in more than 15 randomised clinical trials. A meta-analysis for overall survival showed a statistically significant difference in favour of chemoradiotherapy: relative risk (RR) = 1.20, 95% confidence interval (CI) = 1.14-1.26, p < 0.001, p hetero = 0.21). Disease-free survival was also statistically significantly higher in favour of chemoradiotherapy: RR = 1.26, 95%CI = 1.17-1.35, p < 0.001). The benefit was more pronounced in trials including a higher proportion of stage I and II patients. Concomitant chemoradiotherapy showed a significant benefit for both local control and distant metastasis. Gastrointestinal and haematological toxicities were significantly more frequent in the chemoradiotherapy group. Details of late toxicity were sparse and therefore it was not possible to conclude on an increase of late complication rate with concomitant chemoradiotherapy. The inclusion criteria were not the same in all the trials, resulting in populations with varying distributions in disease stages. In addition, the treatment schemas for both radiotherapy and chemotherapy used in these trials were different. These results were obtained with chemotherapy based on various molecules, including cisplatin, either alone or with other cytotoxic drugs, such as 5-fluorouracil. For a similar level of benefit, the combination of cisplatin, 5-fluorouracil and hydroxyurea was more toxic than cisplatin alone in one trial in which the two protocols were compared. Future randomised trials should also aim to establish optimal chemotherapy regimens for combination with radiotherapy.
Antineoplastic Agents↗
Outcomes after combined therapy including surgical resection in patients with epithelial ovarian cancer recurrence(s) exclusively in lymph nodes.
BACKGROUND: The aim was to study the prognosis for and survival of patients treated with combined therapy (including surgical resection) for nodal recurrences from epithelial ovarian cancer (EOC). METHODS: This was a retrospective study of a group of 12 patients with a recurrence from EOC, a priori, exclusively located in lymph node(s). All patients underwent surgical resection of nodal metastases, followed by adjuvant therapy. RESULTS: The median age of patients was 51 (range, 42-71) years. The initial disease stages were as follows: stage IA, n = 5; stage IIA, n = 1; and stage IIIC, n = 6. The median interval between the end of initial treatment and the nodal relapse was 21 (range, 6-72) months. The recurrence was located in the abdominal nodes in 10 patients (pelvic and/or para-aortic area) and was extra-pelvic in one patient, and the last patient had concomitant para-aortic and supraclavicular nodal involvement. Ten patients received postoperative chemotherapy and two had radiation therapy (one patient received both treatments). Eight patients relapsed and four did not. To date, three patients have died of the disease, three are alive with persistent disease, and six are alive and disease-free (including two patients who were treated by surgical resection after relapses twice in abdominal nodes). Five-year overall survival from the time of treatment of recurrent disease is 71% (confidence interval, 41%-90%). CONCLUSIONS: The prognosis of patients with an a priori isolated nodal recurrence from EOC was good in this group of treated with surgical resection followed by chemoradiation or radiation therapy. This finding argues in favor of proposing surgical resection in such patients.
Adult↗
Audit of effectiveness of routine follow-up clinics after radiotherapy for cancer: a report of the REACT working group of ESTRO.
BACKGROUND AND PURPOSE: The European Society for Therapeutic Radiology and Oncology was funded by the EU for a project on recording providing education, and ameliorating the consequences of treatment (REACT). An European audit was carried out as part of which to assess the usefulness of current follow-up practices. PATIENTS AND METHODS: Over a 4-month period in 15 cancer centres in 10 countries, patients attending for routine follow-up completed a questionnaire covering their expectations of and satisfaction with the visit. This was matched with a questionnaire completed by the physician about the content and usefulness of the consultation. The feasibility of a short toxicity scale developed by Dische and Saunders was also investigated. RESULTS: In total, 2303 matched questionnaires were analysed. Forty percent of the patients had symptoms or medical problems related to their disease. In 18% there was a positive finding on clinical examination. In 28% investigations were undertaken part of departmental routine practice. Ten percent of the investigations showed an abnormal result. Ninety nine percent of physicians and 85% of the patients expressed satisfaction. Using the short toxicity scale rates of recording toxicity could be increased from 28 to 93%. CONCLUSIONS: There is wide variation in follow-up practices among European centres. There was a low incidence of positive findings clinically or with routine investigations. A simple scale for recording morbidity has proved easy to use by departments, which have not routinely used one of the standard measures. Further work will attempt to produce an European guideline for effective routine follow-up after radiotherapy.
Ambulatory Care Facilities↗
Bladder-conserving surgery and interstitial brachytherapy for lymph node negative transitional cell carcinoma of the urinary bladder: results of a 28-year single institution experience.
BACKGROUND AND PURPOSE: We retrospectively analyzed results for lymph node negative transitional cell carcinoma of the bladder treated with brachytherapy. PATIENTS AND METHODS: From 1975-2002, 58 patients received preoperative external irradiation, partial cystectomy (in 69%), iliac node dissection, and iridium-192. Pathologic stage was: 10 pT1, 41 pT2, and 7 pT3. A median total brachytherapy dose of 60 Gy was delivered to the tumor bed. RESULTS: Mean follow-up was 76 months (range, 0.5-296). Tumor stage significantly impacted cause-specific and disease-free survival (P=0.02). Eight pT1 patients were free of disease and 2 died of other cause. For pT2 patients, 5-year cause-specific and overall survival rates were, respectively, 70% (CI 95%: 53-87) and 60% (CI 95%: 43-77). Three pT3 patients died of cancer. For the pT2 patients, the probability of 5-year local control was 65% (CI 95%: 47-83) and being alive without disease with a functional bladder, 50% (CI 95%: 33-67). Previous transurethral resection (TUR) increased the bladder relapse risk among pT2 patients (P=0.03). Twelve patients had severe acute complications and 5 had severe late effects. A high dose of external irradiation increased risk of late complications (P=0.01). Most complications occurred in patients treated before 1985. CONCLUSIONS: Highly select patients presenting with pT2 tumors less than 5 cm with no history of previous TUR may be successfully treated with low-dose external irradiation, limited partial cystectomy, and interstitial brachytherapy. High-risk pT1 patients may also benefit. Postoperative complications and late side effects are minimized with modern management. We recommend lifelong cystoscopic surveillance, with prompt surgical salvage for recurrence.
Aged↗
First case of a centropelvic recurrence after radical trachelectomy: literature review and implications for the preoperative selection of patients.
BACKGROUND: To report the first case of a centropelvic recurrence in a patient who underwent a radical trachelectomy (RT) for a stage IB1 cervical carcinoma. CASE: A 32-year-old woman presented with a stage IB1 adenocarcinoma that was treated by radical trachelectomy. The tumor measured 21 x 20 mm. Minimal lymphatic space involvement was observed close to the tumor associated with 30 negative nodes and free margins. The upper free margin measured only 5 mm. Twenty-six months after the surgical procedure, the patient became pregnant. Clinical examination and pap smears were normal 2 months prior. During the first trimester, ultrasonography depicted a suspicious lesion in the bladder. Abdomino-pelvic magnetic resonance imaging (MRI) demonstrated a suspicious 20-mm tumor in the bladder associated with suspicious common iliac nodes. Cystoscopy and biopsies were carried out which confirmed recurrent disease. The patient received external radiation therapy combined with concomitant chemotherapy. CONCLUSIONS: More data are required to establish what is the safety distance between the tumor and the uterine transection. A distance of 5 mm or less is likely to be too limited for radical trachelectomy to be accepted as treatment for cervical cancer.
Adenocarcinoma↗
[Role of radiotherapy in recurrent gliomas].
Intracranial gliomas account for less than 2% of primary solid tumors in adults, but are among the most frequent causes of death from cancer in children. Their increasing incidence and the weak impact of treatments on the prognosis justify all the efforts expended to improve results. Surgery, radiation therapy (RT) and chemotherapy are proposed as first-line therapy, according to indications and modalities that remain controversial. In this palliative setting, the only consensus is to search for an optimal efficacy/toxicity ratio. Finally, after a very variable duration of local control depending on the histologic type, recurrence is virtually inevitable, with mainly local progression. The prognosis is then generally dismal, with a median survival of less than 6 months. Although re-operation is efficient for the rapid relief of symptoms, it is often rejected. After or in the absence of surgery, different chemotherapy schedules are proposed according to the histologic type and the patient's general status and objective response rates are very limited, except in the case of oligodendrogliomas. Re-irradiation has a rather bad reputation: even as first-line therapy, total doses never exceed 60 Gy in 30 fractions of 2 Gy over six weeks (conventional fractionation). The main reasons are concerns about increasing unacceptable late neurologic complications and the absence of a demonstrated dose-effect beyond this threshold. However, some arguments have led clinicians to consider lifting the ban on re-irradiation. Among adult patients receiving focal RT for low-grade gliomas, late neurologic toxicity was recently evaluated prospectively using a battery of neurocognitive tests. Compared with the initial status, no significant deleterious effects were observed with a follow-up of at least 3 years. In addition, studies on primates demonstrated that the spinal cord was capable of repairing, at least partially, RT-induced injury. There appears to be room for further irradiation: the results of re-irradiation in more than 300 patients have been documented. The techniques used, patient selection and re-irradiation modalities reported were varied: interstitial brachytherapy or intraoperative-RT within the surgical bed, conformal 3D RT, stereotactic-RT delivered in one or several fractions. Treatment efficacy and toxicity endpoints were very heterogeneous. Nevertheless, with a clearly defined prospective assessment, re-irradiation seems possible without any unacceptable clinical neurotoxicity under the following conditions: a good general status (WHO 0-1); at least a one-year disease-free interval; an initial WHO grade 2 or 3 histology with a maximal tumor diameter not exceeding 3 cm. In this very selective setting, re-irradiation is possible at a dose of 30 to 40 Gy, if possible in stereotactic mode, with a hypofractionated schedule (less than 4 Gy/fraction). Median survival exceeding one year is expected, the main endpoint being the control of symptoms and quality of life.
Age Factors↗
Fibrogenic signals in patients with radiation enteritis are associated with increased connective tissue growth factor expression.
PURPOSE: To investigate the expression of a new fibrogenic cytokine the connective tissue growth factor (CTGF) in intestinal radiation fibrosis and to characterize the mesenchymal cell subtypes involved in CTGF synthesis and collagen deposition. METHODS AND MATERIALS: Sixteen patients with radiation enteritis that occurred after radiotherapy for pelvic malignancies and 6 with histologically normal bowel entered the study. Immunohistochemistry, Western blot analysis, and real-time reverse transcriptase-polymerase chain reaction were performed to study CTGF expression, along with other known markers of radiation fibrosis: the pro-fibrogenic cytokine transforming growth factor (TGF)-beta1 and phenotypic markers of the fibroblast differentiation the alpha-sm actin (A), vimentin (V), and desmin (D). Finally, the collagen accumulation was measured by Sirius red staining and colorimetric assay. RESULTS: Radiation enteritis was characterized by increased collagen content within the intestinal wall. CTGF immunoreactivity, protein, and mRNA level were increased in radiation enteritis compared with the healthy bowel. On the contrary, no increase of the TGF-beta1 mRNA level was observed in radiation enteritis compared with healthy bowel, and the level of TGF-beta protein was slightly increased in radiation enteritis. A co-localization of CTGF immunoreactivity and collagen deposition was found in the extracellular matrix and subtypes of activated mesenchymal cells with a fibroblast phenotype (V(+)/D(-)/A(-)) and myofibroblast phenotype (V(+)/D(-/+)/A(+)). CONCLUSION: The increased level of CTGF protein and mRNA associated with the accumulation of fibroblasts/myofibroblasts and collagen deposition were parts of the fibrogenic signals involved in the persistence of late intestinal radiation fibrosis.
Adult↗
[Standards, Options and Recommendations for the management of invasive cervical cancer patients (non metastastic)].
CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French cancer centers and specialists from French public university and general hospitals and private clinics. Its main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop, according to the definitions of the Standards, Options and Recommendations, clinical practice guidelines for the management of invasive cervical cancer patients. Methods : Data were identified by searching Medline and the personal reference lists of members of the expert groups, then submitted for review to independent reviewers. RESULTS: This is a synthesis of the Standards, Options and Recommendations elaborated by a working group of experts. Pretherapeutic assessment, classification, diagnosis, therapeutic modalities (surgery, radiotherapy, radiochemotherapy, chemotherapy), therapeutic strategies by disease stage and follow-up are covered. Algorithms for the management of patients are also included.
Algorithms↗