Journal

Cancer/Radiothérapie

Papers (32)

Evaluation of adjuvant vaginal vault brachytherapy in early stage cervical cancer patients

Adjuvant external beam radiotherapy (EBRT) was shown to decrease pelvic relapses in patients with an early stage cervical cancer and intermediate-risk histopathological prognostic factors, at the cost of increased bowel morbidity. We examined the feasibility and results of adjuvant brachytherapy alone as an alternative to EBRT in this situation. Medical records of consecutive patients receiving adjuvant brachytherapy between 1991 and 2018 for an early stage cervical cancer were examined. Patients were included if they presented a pT1a2N0 or pT1b1N0 disease following radical colpohysterectomy. Adjuvant vaginal wall brachytherapy (without EBRT) was indicated because of a tumor size≥2cm and/or presence of lymphovascular space invasion (LVSI). Patients received 60Gy to 5mm of the vaginal wall, through low-dose or pulse-dose rate technique. Patients' outcome was examined for disease control, toxicities and prognostic factors. A total of 40 patients were included. Eight patients (20%) had LVSI, 26 patients (65%) had a tumor size≥2cm. With median follow-up time of 42.0 months, 90% of patients were in complete remission and four patients (10%) experienced tumor relapse, all in the peritoneal cavity, and associated with synchronous pelvic lymph node failure in 2/4 patients. No vaginal or isolated pelvic nodal failure was reported. At 5 year, overall survival was 83.6% (CI95%: 67.8-100%) and disease-free survival was 85.1% (CI95%: 72.6-99.9%). In univariate analysis, probability of relapse correlated with tumor size≥3cm (P=0.004). No acute or late toxicity grade more than 2 was reported. Brachytherapy alone was a well-tolerated adjuvant treatment for selected patients with intermediate risk factors. The risk of relapse in patients with tumor size≥3cm was however high, suggesting that EBRT is more appropriate in this situation.

Correlation between changes in the number of peripheral blood lymphocytes and survival rate in patients with cervical cancer after radio-chemotherapy

This study aimed to compare the absolute numbers of various types of lymphocytes in the peripheral blood before and after chemotherapy following radio-chemotherapy in patients with cervical cancer, so as to explore the correlation between the changes in the absolute numbers of peripheral various types of lymphocytes and the overall survival rate of patients. Data of 205 patients with cervical cancer admitted to the hospital from June 2014 to August 2016 were retrospectively analyzed. These patients underwent concurrent radio-chemotherapy, followed by chemotherapy. The absolute numbers of peripheral blood lymphocytes and subtypes were compared before and after re-chemotherapy. For patients with a good prognosis, the number of lymphocytes, T cells, and cytotoxic T cells (Tc) significantly decreased (P<0.05) after re-chemotherapy, while this phenomenon was not observed in patients with poor prognosis. Kaplan-Meier univariate analysis showed that patients with cervical cancer who had an advanced FIGO stage before treatment, presence of lymph node metastasis, and increased numbers of Tc and T helper cells after re-chemotherapy showed a low 30-month survival rate; the overall log-rank analysis showed significant differences (P<0.05). Multivariate Cox proportional hazards regression analysis, presence of lymph node metastasis: HR=9.718, P=0.002, 95% CI=0.183-0.679; Tc grouping: HR=3.239, P=0.0.072, 95% CI=0.950-03.347; Th group: HR=3.197, P=0.074, 95% CI=0.943-3.564. After radio-chemotherapy, in patients with advanced cervical cancer, the change in the numbers of peripheral blood Tc and Th before and after re-chemotherapy was associated with the 30-month overall survival rate of patients. It can be considered as a predictor of the survival of patients with advanced cervical cancer.

Glassy cell carcinoma of the uterine cervix: 20-year experience from a comprehensive cancer center

Glassy cell carcinoma (GCC) of the uterine cervix is a rare entity. This study aims at describing the clinical characteristics and outcomes of cervical GCC patients treated in a comprehensive cancer center. We retrospectively reported patients and tumors characteristics, therapeutic management, overall survival (OS), progression-free progression (PFS), relapse rates, and toxicities. Between 1994 and 2014, 55 patients were treated with curative intent. The median age at diagnosis was 41 years (range, 20-68). Among 22 patients with early stage tumors (IA2-IB1-IIA1), 17 had preoperative brachytherapy, followed by radical hysterectomy. Among 33 patients with locally advanced disease (≥IB2), 32 underwent chemoradiation±brachytherapy boost. After a median follow-up of 5.4 years (range, 0.15-21.7 years), 18/55 (33%) patients experienced tumor relapse. Local recurrence occurred in 2/22 (9%) patients with early disease (treated with upfront surgery) and in 3/32 (9%) patients with locally advanced disease. Most frequent relapses were distant, occurring in a total of 11/55 patients (20%). PFS rates at 5-year were 86.4% (95% CI: 63.4-95.4) for early stage versus 75.9% (95% CI: 55.2-89.2) for locally advanced stages, respectively (P=0.18). Large cohort data are warranted to guide the optimal management of GCC. From this retrospective analysis, a multimodal approach yielded to good disease control in early stages tumors. Given the high-risk of distant failure, consideration should be given to adjuvant chemotherapy in locally advanced disease.

Impact of external beam pelvic radiotherapy of endometrial carcinoma: A focus on chronic digestive toxicity

The standard treatment for endometrial cancer is surgery, although depending on the risk factors, adjuvant radiation therapy may also be given. It is proposed for high-risk carcinomas for which an improvement in progression-free survival though not overall survival has been shown. However, despite the development of radiotherapy treatments with intensity modulation and image guidance, adjuvant radiation therapy remains toxic to the digestive system. We aimed to investigate the incidence of digestive toxicity and the presence of any predictive factors. Data were retrospectively collected from patients treated with adjuvant radiotherapy for endometrial carcinoma at the Institut de cancérologie de Lorraine and centre hospitalier Émile-Durkheim between January 2010 and October 2016 and analyzed to identify factors associated with chronic digestive toxicity. One hundred and thirty-nine patients received a total dose of 50Gy fractionated into 25 sessions, five per week for five weeks. The median follow-up after irradiation completion was 38 months. The incidence of gastrointestinal and rectal toxicity in all patients treated with pelvic irradiation for endometrial carcinoma was 11.1% (95% confidence interval [95%CI]: 5.4-19%) for grade 3-4 and 25.6% (95%CI: 17.0-34.9%) for grade 2-4. No factor was found to be significantly predictive of chronic digestive toxicity. At five years, the overall survival was 74.3%, (95%CI: 65.3-81.4%), progression-free survival was 69.6% (95%CI: 60.1-77.3%) and incidence of pelvic recurrence was 7.9% (95%CI: 3.8-13.9%). Our results confirmed that pelvic radiotherapy can induce a relatively high rate of digestive toxicity but failed to identify relevant factors able to predict it.

Automatic segmentation of high-risk clinical target volume and organs at risk in brachytherapy of cervical cancer with a convolutional neural network

This study aimed to design an autodelineation model based on convolutional neural networks for generating high-risk clinical target volumes and organs at risk in image-guided adaptive brachytherapy for cervical cancer. A novel SERes-u-net was trained and tested using CT scans from 98 patients with locally advanced cervical cancer who underwent image-guided adaptive brachytherapy. The Dice similarity coefficient, 95th percentile Hausdorff distance, and clinical assessment were used for evaluation. The mean Dice similarity coefficients of our model were 80.8%, 91.9%, 85.2%, 60.4%, and 82.8% for the high-risk clinical target volumes, bladder, rectum, sigmoid, and bowel loops, respectively. The corresponding 95th percentile Hausdorff distances were 5.23mm, 4.75mm, 4.06mm, 30.0mm, and 20.5mm. The evaluation results revealed that 99.3% of the convolutional neural networks-generated high-risk clinical target volumes slices were acceptable for oncologist A and 100% for oncologist B. Most segmentations of the organs at risk were clinically acceptable, except for the 25% sigmoid, which required significant revision in the opinion of oncologist A. There was a significant difference in the clinical evaluation of convolutional neural networks-generated high-risk clinical target volumes between the two oncologists (P<0.001), whereas the score differences of the organs at risk were not significant between the two oncologists. In the consistency evaluation, a large discrepancy was observed between senior and junior clinicians. About 40% of SERes-u-net-generated contours were thought to be better by junior clinicians. The high-risk clinical target volumes and organs at risk of cervical cancer generated by the proposed convolutional neural networks model can be used clinically, potentially improving segmentation consistency and efficiency of contouring in image-guided adaptive brachytherapy workflow.

Comparaison entre Stump Cylinder et moule personnalisé, effet de la forme de l’applicateur sur la distribution de dose

The purpose of this study was to compare the efficacy of two applicators used in high dose rate vaginal brachytherapy. The first is the Stump Cylinder used in the "brachycenter" department at the Middle East Institute of Health in Lebanon and the second is the custom mold used in the radiotherapy department at Tenon Hospital in France. A comparison of the clinical target volume and the doses received by the rectum and bladder was performed in order to determine the best method of treatment and to optimize the dose distribution. 95 patients were treated in both departments. The average values of the D95% dose received by the CTV were respectively 89.43% for the Stump Cylinder and 110.16% for the custom mold. The conformity index was 0.84 for the Stump Cylinder while it was 0.97 for the custom mold, which ensures a better dose distribution. For the rectum, the maximum dose D2cc taken by volume was 71.23% for the Stump Cylinder and 79.51% for the custom mold. The bladder was better protected with Stump Cylinder with a D2cc value of 65.81% against 94.88% for the custom mold. The underdosing obtained using the Stump Cylinder was due to the shape of upper part of the cylinder which was not conform with the shape of the vaginal vault in women. A better protection of the organs at risk was observed with the Stump Cylinder since the dose taken by the rectum and bladder using a custom mold can reach the tolerance limits.

Adenoid cystic carcinoma of Bartholin's gland, a case report with genomic data and literature review

Adenoid cystic carcinoma of the Bartholin's gland (ACCBG) is a rare, slowly but aggressive malignancy. We reported the case of a 31-year-old woman who was treated by local excision and then hemi-vulvectomy, with positive margins and perineural invasion. Radiation therapy (RT) was then performed delivering 45Gy in 25 fractions in bilateral inguinal lymph nodes and 64.8Gy in 36 fractions on the vulvar area. After 30 months, there was no local relapse (LR) but the patient presented a histologically documented lung recurrence. Genomic profiling of the tumor showed a MYB-NFIB fusion transcript and a somatic mutation of PLCG1. A treatment by Lenvatinib was started. We conducted a literature review of 100 published cases. Patients were mainly treated by radical vulvectomy (30%), hemi-vulvectomy (17%), wide or local excision (21% and 24%, respectively) or other. Forty-four percent of patients received postoperative RT, more frequently in case of positive margin (71.9% versus 29.5%). RT may reduce the risk of LR regardless of margin status, with 15.4% vs. 41.9% of LR with or without RT, respectively, in patients with negative margins, and 13% vs. 33.3% of LR with or without RT, respectively, in patients with positive margins. The risk of relapse of any type was 40.9% in patients who received adjuvant RT vs. 48.2% in patients who did not. Median time to relapse was 24 months (range 6-156 months). The most frequent metastatic sites were lung (76.7%) and bone (26.7%). Optimal treatment for ACCBG is still not clearly defined but pooling the data from published case report help us better understand this rare disease and help in the therapeutic decision.

Transformative clinical trials in gynaecologic radiation oncology in 2023–2024: Shaping modern treatment practices

The field of gynaecologic oncology has evolved rapidly in recent years, largely driven by advances in both radiotherapy and systemic therapies. These innovations have reshaped the management of key gynaecologic cancers, including cervical, endometrial, vaginal, and vulvar cancers, leading to more personalized and effective treatment approaches. This review explores pivotal clinical trials conducted between 2023 and 2024 that have potentially modified current practices. Through an extensive analysis of randomized controlled trials and meta-analyses, we examine the evolving role of radiotherapy, the integration and sequencing of immunotherapy, and the refinement of neoadjuvant and adjuvant treatments based on molecular classifications. The combination of immunotherapy with chemoradiotherapy has shown promising outcomes, particularly in patients with locally advanced cervical cancer. For endometrial cancer, molecular profiling has enabled a more precise classification of tumour subtypes, leading to better-targeted adjuvant therapies that reduce unnecessary interventions and increase treatment efficacy. In parallel, radiotherapy has advanced with the increasing use of modern techniques such as intensity-modulated radiotherapy and more recently the developments of adaptive treatments in order to minimize exposure to healthy tissue, thereby reducing toxicity and enhancing patient quality of life. Integration of image-guided brachytherapy and expansion of capabilities with newer generation of brachytherapy applicators have also increased possibilities to achieve efficient local treatments, including in very advanced cases. However, despite progress in common gynaecologic cancers, the management of rare cancers such as vulvar and vaginal cancers continues to face challenges due to limited clinical research and treatment data. This review highlights the transformative potential of these innovations and emphasizes the need for continued research and personalized treatment strategies to optimize patient outcomes in gynaecologic oncology.

Cancer de l’endomètre de stade localisé : la perspective d’une désescalade thérapeutique guidée par la classification moléculaire

In Europe, endometrial cancer is the fourth most common cancer among women. The majority of patients are diagnosed at a localized stage. For these patients, the standard of care is based on an hysterectomy with salpingo oophorectomy±lymph node staging. Through the assessment of histopathologic features, risk groups are determined: low, intermediate, high-intermediate, and high risk. Adjuvant strategies are guided by these risk groups. While the prognosis of low-risk and high-risk is well known, that of intermediate and high-intermediate risk is more heterogeneous, and the therapeutic index of adjuvant treatments is more questionable. Several trials (PORTEC [Post Operative Radiation Therapy in Endometrial Carcinoma] I, GOG [Gynecologic Oncology Group] 99, ASTEC [A Study in the Treatment of Endometrial Cancer] EN.5, PORTEC II, Sorbe et al trial) have assessed observation, vaginal cuff brachytherapy and/or pelvic external beam radiotherapy in this population. Vaginal cuff brachytherapy reduces the local recurrence rate, and pelvic external beam radiotherapy the pelvic recurrence rate. However, no benefit in terms of overall survival or occurrence of distant metastases is highlighted. Compared to observation, brachytherapy and above all external beam radiotherapy are associated with an increased morbidity, and with a decreased quality of life. In order to improve the therapeutic ratio and to optimize medico-economic decisions, therapeutic de-escalation strategies, based on the molecular profiles, are emerging in clinical trials, and in the recommendations for the management of intermediate and high-intermediate risk endometrial cancers. The four main molecular profiles highlighted by the genomic analyzes of The Cancer Genome Atlas (TCGA) - POLE (polymerase epsilon) mutation, non-specific molecular profile, MMR (MisMatch repair) deficiency, and p53 mutation - but also the quantification of lymphovascular space invasion (absent, focal or substantial), and the assessment of L1CAM (L1 cell adhesion molecule) overexpression represent growing concerns. Thus, the use of molecular-integrated risk profile to determine the best adjuvant treatment represent a major way to personalize adjuvant treatment of endometrial cancers, with therapeutic de-escalation opportunity for around half of the high-intermediate risks. However, in the absence of prospective data, inclusion in clinical trials assessing molecular profile-based treatment remains the best therapeutic opportunity.

Publisher

Elsevier BV

ISSN

1278-3218