Intermediate-risk endometrial cancer treated with adjuvant brachytherapy using single dosimetric planning: long-term outcome and toxicity assessment.

OBJECTIVE: Brachytherapy of the vaginal dome is the recommended adjuvant treatment for intermediate-risk endometrial cancer. This study assessed the results of dosimetric planning of high-dose-rate brachytherapy exclusively in the first treatment session. STUDY DESIGN: This retrospective study included all patients who underwent hysterectomy for endometrial cancer followed by adjuvant brachytherapy of the vaginal dome between 2012 and 2015. Local recurrence rates, overall survival (OS) rates, recurrence-free survival (RFS) rates, and related acute and late toxicity rates were evaluated. RESULTS: This analysis included 250 patients, of whom 208 were considered to be at high-intermediate risk of disease recurrence. After a median follow-up of 56 months, the cumulative incidence of local recurrence was 4.8% at 3 years [95% confidence interval (CI) 2.8-8.3] and 7.8% at 5 years (95% CI 4.8-12.6). The 5-year OS rate was 86.2% (95% CI 80.6-90.3), and the 5-year RFS rate was 77.5% (95% CI 71.1-82.7). Acute toxicity occurred in 20 (8%) patients, of which two patients had grade ≥3 toxicity. Only one patient (0.4%) presented with late grade ≥3 toxicity. CONCLUSION: These findings confirm the tolerability of this brachytherapy approach, indicating minimal cases of late grade ≥3 toxicity, associated with a good 5-year OS rate. With the advent of molecular prognostic factors, the current focus revolves around discerning those individuals who gain the greatest benefit from adjuvant therapy, and tailoring treatment more effectively.

Interstitial needles versus intracavitary applicators only for locally advanced cervical cancer: results from real-life dosimetric comparisons.

Background and purpose: Image-guided adapted brachytherapy (IGABT) is superior to other radiotherapy techniques in the treatment of locally advanced cervical cancer (LACC). We aimed to investigate the benefit of interstitial needles (IN) for a combined intracavitary/interstitial (IC/IS) approach using IGABT over the intracavitary approach (IC) alone in patients with LACC after concomitant external beam radiotherapy (EBRT) and chemotherapy. Materials and methods: We included consecutive patients with LACC who were treated with IC/IS IGABT after radiochemotherapy (RCT) in our retrospective, observational study. Dosimetric gain and sparing of organs at risk (OAR) were investigated by comparing the IC/IS IGABT plan with a simulated plan without needle use (IC IGABT plan) and the impact of other clinical factors on the benefit of IC/IS IGABT. Results: Ninety-nine patients were analyzed, with a mean EBRT dose of 45.5 ± 1.7 Gy; 97 patients received concurrent chemotherapy. A significant increase in median D90% High Risk Clinical target volume (HR-CTV) was found for IC/IS (82.8 Gy) vs IC (76.2 Gy) (p < 10-4). A significant decrease of the delivered dose for all OAR was found for IC/IS vs IC for median D2cc to the bladder (77.2 Gy), rectum (68 Gy), sigmoid (53.2 Gy), and small bowel (47 Gy) (all p < 10-4). Conclusion: HR-CTV coverage was higher with IC/IS IGABT than with IC IGABT, with lower doses to the OAR in patients managed for LACC after RCT. Interstitial brachytherapy in the management of LACC after radiotherapy provides better coverage of the target volumes, this could contribute to better local control and improved survival of patients.

Impact of surgery and chemotherapy in ovarian sex cord-stromal tumors from the multicentric Salomé study including 469 patients. A TMRG and GINECO group study.

OBJECTIVE: Identifying prognostic factors and evaluating the impact of adjuvant chemotherapy in patients with sex cord stromal tumors (SCST) is crucial. In this study, we aimed to address these challenges. METHODS: We conducted a retrospective analysis of data from 13 centers of the French Rare malignant gynecological tumors (TMRG) network. We enrolled 469 adult patients with malignant SCST who received upfront surgery since 2011 to July 2015. RESULTS: 75% were diagnosed with adult Granulosa cell tumors, and 23% had another subtype. With a median follow-up of 6.4 years, 154 patients (33%) developed a first recurrence, 82 (17%) two recurrences, and 49 (10%) three recurrences. Adjuvant chemotherapy was administered in 14.7% of patients at initial diagnosis. In relapse, perioperative chemotherapy was administered in 58.5%, 28.2%, and 23.8% of patients, respectively, in the first, second, and third relapse. In the first-line therapy, age under 70 years, FIGO stage, and complete surgery were associated with longer progression-free survival (PFS). Chemotherapy had no impact on PFS in early-stage disease (FIGO I-II). The PFS was similar using BEP or other chemotherapy regimens (HR 0.88 [0.43; 1.81]) in the first-line therapy. In case of recurrence, PFS was statistically prolonged by complete surgery, but perioperative chemotherapy use did not impact PFS. CONCLUSION: Chemotherapy use did not impact survival in the first-line or relapse setting in SCST. Only surgery and its quality demonstrated benefit for PFS in ovarian SCST in any lines of treatment.

Results of a 20 Year Retrospective Analysis of Early-Stage Cervical Cancer: Should 3 cm Be Considered the New Ariadne's Thread in Early Cervical Cancer Treatment?

(1) This study aims to evaluate the overall survival (OS) and recurrence-free survivals (RFS) and assess disease recurrence of early-stage cervical cancer (ESCC) patients treated with minimally invasive surgery (MIS). (2) This single-center retrospective analysis was performed between January 1999 and December 2018, including all patients managed with MIS for ESCC. (3) All 239 patients included in the study underwent pelvic lymphadenectomy followed by radical hysterectomy without the use of an intrauterine manipulator. Preoperative brachytherapy was performed in 125 patients with tumors measuring 2 to 4 cm. The 5-year OS and RFS rates were 92% and 86.9%, respectively. Multivariate analysis found two significant factors associated with recurrence: previous conization with HR = 0.21, p = 0.01, and tumor size > 3 cm with HR = 2.26, p = 0.031. Out of the 33 cases of disease recurrence, we witnessed 22 disease-related deaths. Recurrence rates were 7.5%, 12.9%, and 24.1% for tumors measuring ≤ 2 cm, 2 to 3 cm, and > 3 cm, respectively. Tumors ≤ 2 cm were mostly associated with local recurrences. Tumors > 2 cm were frequently associated with common iliac or presacral lymph node recurrences. (4) MIS may still be considered for tumors ≤ 2 cm subject to first conization followed by surgery with the Schautheim procedure and extended pelvic lymphadenectomy. Due to the increased rate of recurrence, a more aggressive approach might be considered for tumors > 3 cm.

Prophylactic Radical Fimbriectomy with Delayed Oophorectomy in Women with a High Risk of Developing an Ovarian Carcinoma: Results of a Prospective National Pilot Study.

Risk-reducing salpingo-oophorectomy is the gold standard for the prophylaxis of ovarian cancer in high-risk women. Due to significant adverse effects, 20-30% of women delay or refuse early oophorectomy. This prospective pilot study (NCT01608074) aimed to assess the efficacy of radical fimbriectomy followed by a delayed oophorectomy in preventing ovarian and pelvic invasive cancer (the primary endpoint) and to evaluate the safety of both procedures. The key eligibility criteria were pre-menopausal women ≥35 years with a high risk of ovarian cancer who refused a risk-reducing salpingo-oophorectomy. All the surgical specimens were subjected to the SEE-FIM protocol. From January 2012 to October 2014, 121 patients underwent RF, with 51 in an ambulatory setting. Occult neoplasia was found in two cases, with one tubal high-grade serous ovarian carcinoma. Two patients experienced grade 1 intraoperative complications. No early or delayed grade ≥3 post-operative complications occurred. After 7.3 years of median follow-up, no cases of pelvic invasive cancer have been noted. Three of the fifty-two patients developed de novo breast cancer. One BRCA1-mutated woman delivered twins safely. Twenty-five patients underwent menopause, including fifteen who had received chemotherapy for breast cancer, and twenty-three underwent menopause before the delayed oophorectomy, while two did not undergo a delayed oophorectomy at all. Overall, 46 women underwent a delayed oophorectomy. No abnormalities were found in any delayed oophorectomy specimens. Radical fimbriectomy followed by delayed oophorectomy appears to be a safe and well-tolerated risk-reducing approach, which avoids early menopause for patients with a high risk of breast and ovarian cancer.

Stage I Clear Cell and Serous Uterine Carcinoma: What Is the Right Adjuvant Therapy?

This single-center study aimed to retrospectively evaluate the survival outcomes of patients with FIGO stage I clear cell and serous uterine carcinoma according to the type of adjuvant treatment received. The data were collected between 2003 and 2020 and only patients with stage I clear cell or serous uterine carcinoma treated with primary surgery were included. These were classified into three groups: No treatment or brachytherapy only (G1), radiotherapy +/- brachytherapy (G2), chemotherapy +/- radiotherapy +/- brachytherapy (G3). In total, we included 52 patients: 18 patients in G1, 16 in G2, and 18 in G3. Patients in the G3 group presented with poorer prognostic factors: 83.3% had serous histology, 27.8% LVSI, and 27.8% were FIGO stage IB. Patients treated with adjuvant radiotherapy showed an improved 5-year overall survival (OS) (p = 0.02) and a trend towards an enhanced 5-year progression-free survival (PFS) (p = 0.056). In contrast, OS (p = 0.97) and PFS (p = 0.84) in the chemotherapy group with poorer prognostic factors, were similar with increased toxicity (83.3%). Radiotherapy is associated with improved 5-year OS and tends to improve 5-year PFS in women with stage I clear cell and serous uterine carcinoma. Additional chemotherapy should be cautiously considered in serous carcinoma cases presenting poor histological prognostic factors.

Conservative treatment of glassy cell cervical cancer: A case report.

Glassy cell carcinoma (GCC) constitutes a rare yet histologically aggressive subtype of cervical cancer known for its rapid proliferation and high risk of recurrence and metastasis. Due to its low prevalence, the medical literature lacks large retrospective and prospective studies, and thus, no standardized management has been defined. The recommended treatment for GCC is radical hysterectomy with bilateral pelvic lymphadenectomy; however, since it mainly affects young women of reproductive age, data in the literature suggest conservative management, such as radical trachelectomy. The present report describes the cases of 2 young patients treated conservatively with pelvic lymphadenectomy and radical trachelectomy for early-stage GCC of the cervix. The first patient was a 37-year-old patient who presented a 15-mm GCC tumor [International Federation of Gynecology and Obstetrics (FIGO) stage IB1], and the second patient was a 23-year-old patient who presented a 14-mm GCC tumor (FIGO stage IB1). The first patient presented early vaginal recurrence 3 months postoperatively, which was treated with concomitant pelvic chemoradiation (45 Gy) followed by vaginal and uterine brachytherapy (15 Gy). The second patient presented internal iliac nodal recurrence 1 year after treatment, which was treated by carboplatin-paclitaxel-Avastin-based chemotherapy, followed by laparoscopic paraaortic lymph node dissection and pelvic chemoradiation (45 Gy). Both patients were tumor-free after 5 and 6 years, respectively. Due to the aggressiveness of GCC of the cervix and its high risk of recurrence, conservative treatment should be considered cautiously and should not be the standard of care.

Prognostic impact of tumor size reduction assessed by magnetic resonance imaging after radiochemotherapy in patients with locally advanced cervical cancer.

Objective: Pelvic magnetic resonance imaging (MRI) is a key exam used for the initial assessment of loco-regional involvement of cervical cancer. In patients with locally advanced cervical cancer, MRI is used to evaluate the early response to radiochemotherapy before image-guided brachytherapy, the prognostic impact of which we aimed to study. Methods: Patients with locally advanced cervical cancer treated using concomitant radiochemotherapy followed by closure treatment between January 2010 and December 2015 were included in this study. Clinical, anatomopathological, radiological, therapeutic, and follow-up data were evaluated. Results: After applying the inclusion and exclusion criteria to the initially chosen 310 patients, 232 were included for evaluation (median follow-up period, 5.3 years). The median age was 50 years (range, 25-83 years), and the median tumor size was 47.5 mm (range, 0-105 mm). Based on the International Federation of Gynaecology and Obstetrics classification system, 9 patients were in stage IB2; 20, IB3; 2, IIA; 63, IIB; 4, IIIA; 7, IIIB; and 127, IIIC1 or higher. The re-evaluation MRI was performed at the median dose of 55.5 Gy, and median reduction in tumor size was 55.2% (range, -20-100%). There was a difference between the disease-free and overall survival rates of the patients with a tumor response greater or lesser than 50%. The risk of recurrence or death reduced by 39% in patients with a tumor size reduction >50%. The overall 5-year survival rate of patients with a response greater and lesser than 50% were 77.7% and 61.5%, respectively. The 5-year disease-free survival rate for these two groups of patients were 68.8% and 51.5%, respectively. Conclusion: Our study confirms the prognostic impact of tumor size reduction using MRI data obtained after radiochemotherapy in patients with locally advanced cervical cancer.

Tumor-Infiltrating Lymphocytes (TILs) in Epithelial Ovarian Cancer: Heterogeneity, Prognostic Impact, and Relationship with Immune Checkpoints.

Epithelial ovarian cancers (EOC) are often diagnosed at an advanced stage with carcinomatosis and a poor prognosis. First-line treatment is based on a chemotherapy regimen combining a platinum-based drug and a taxane-based drug along with surgery. More than half of the patients will have concern about a recurrence. To improve the outcomes, new therapeutics are needed, and diverse strategies, such as immunotherapy, are currently being tested in EOC. To better understand the global immune contexture in EOC, several studies have been performed to decipher the landscape of tumor-infiltrating lymphocytes (TILs). CD8+ TILs are usually considered effective antitumor immune effectors that immune checkpoint inhibitors can potentially activate to reject tumor cells. To synthesize the knowledge of TILs in EOC, we conducted a review of studies published in MEDLINE or EMBASE in the last 10 years according to the PRISMA guidelines. The description and role of TILs in EOC prognosis are reviewed from the published data. The links between TILs, DNA repair deficiency, and ICs have been studied. Finally, this review describes the role of TILs in future immunotherapy for EOC.

Primary or Interval Debulking Surgery in Advanced Ovarian Cancer: a Personalized Decision-a Literature Review.

PURPOSE OF REVIEW: Summarize the writings published in the last 5 years on the management of surgery in the first line of treatment for advanced ovarian cancer. RECENT FINDINGS: For patients with a significant tumor burden, the neoadjuvant chemotherapy therapy (NACT) with interval debulking surgery (IDS) strategy shows comparable efficacy than primary debulking surgery (PDS) in terms of survival in randomized studies with less morbidity. Advanced epithelial ovarian cancer generates more than half cases a recurrence. First-line treatment is based on a chemotherapy regimen combining a platinum-based and a taxane-based, associated with surgery. This review considers papers of last 5 years of timing, thinking tools, and innovation in the management. The choice of strategy, PDS or IDS, would be a personalized recommendation. The challenge is to adapt the timing of the surgery to the patient's characteristics and that of her disease.

Protected Laparoscopic Large Ovarian Cyst Aspiration: A 5-Step Alternative to Laparotomy.

STUDY OBJECTIVE: In this video, we describe a 5-step surgical technique that allows us to safely incise and aspirate the content of large ovarian cysts through a single-port laparoscopic incision. This allows performing laparoscopic oophorectomies instead of large xipho-pubic laparotomies. DESIGN: A stepwise demonstration of the technique with narrated video footage. SETTING: Ovarian masses, especially cysts, are common gynecologic conditions [1]. However, depending on their size, large adnexal cysts are usually managed with transverse or midline laparotomies [2]. This is to prevent cyst ruptures and abdominal contamination and ensure oncological safety of the procedure [3-5]. Different leak-proof aspiration techniques have been described in the literature allowing for safe large cyst aspiration and adnexectomy through a mini-laparotomy incision or via laparoscopy [2,3,6-10]. We describe a 5-step surgical technique allowing for closed aspiration of ovarian intracystic fluid and adnexectomy while respecting oncological safety. INTERVENTIONS: Step 1: Perform diagnostic laparoscopy to rule out peritoneal carcinomatosis contraindicating this procedure and then after cyst exposition, thoroughly dry the cyst wall. Step 1 Bis: Cut the cuff of a sterile glove to prepare a square piece of membrane. Step 2: Place a protective gauze and then apply the surgical glue to the ovarian cyst wall followed by the glove/membrane application. Perform a purse suture through the glove/membrane and the ovarian wall superficially to ensure further adhesion and prevent ovarian fluid spillage. Step 3: Incise the ovarian wall, introduce the aspiration cannula and tighten the purse suture to aspirate the cystic fluid. Step 4: After aspiration is complete, tighten the suture and close the glove to guarantee a closed space and prevent abdominal contamination. Step 5: Perform laparoscopic oophorectomy or cystectomy. Safely remove the specimen in an endoscopic retrieval bag through the trocar incision. CONCLUSION: This technique allows safe laparoscopic large ovarian cysts resections while respecting oncologic safety and preventing intra-abdominal spillage and contamination.

Radical Hysterectomy After the LACC Trial: Back to Radical Vaginal Surgery.

OPINION STATEMENT: Classical radical vaginal hysterectomy first performed by Anton Pawlik in Prague in 1888 and popularized by Frederic Schauta is now a historical technique virtually abandoned due to painful perineal incision, a high rate of urinary dysfunction, and the inability to perform lymph node assessment. However, the heritage of this approach has been still used and taught in a few centers outside their Austrian birthplace. A combined vaginal and laparoscopic approach was developed in the 1990s by French and German surgeons who designed diverse surgical techniques for which a novel classification is proposed. All these techniques are different from the so-called laparoscopically assisted radical vaginal hysterectomy (LARVH), a term widely used for laparoscopic radical hysterectomies with vaginal extraction of the specimen. Interestingly, after the publication of the LACC trial (Laparoscopic Approach to Cervical Cancer), the radical vaginal approach has found a very timely application. The creation of a vaginal cuff before performing radical laparoscopic hysterectomy described in 2007 by Leblanc as "Schautheim" operation can be used as a protective maneuver to avoid tumor spillage and potentially overturn the negative outcome of minimally invasive surgery in early-stage cervical cancer. As a result, the combination of radical vaginal and laparoscopic steps of surgery is one possible evolution after the LACC trial that needs further investigation. The forgotten vaginal surgical technique needs a specific learning curve. The creation of a vaginal cuff should be mastered by every gynecological oncologist.

Laparoscopic ureteral reimplantation applying the modified psoas hitch and Lich-Gregoir onlay technique: a 10-step surgical video.

INTRODUCTION AND HYPOTHESIS: Describe the surgical technique of laparoscopic ureterovesical reimplantation applying the modified psoas hitch with Lich-Gregoire onlay technique to manage a distal ureteral fistula after a hysterectomy for a gynecologic malignancy. MATERIALS AND METHODS: This video illustrates the surgical technique of laparoscopic ureteral reimplantation applying the modified psoas hitch with Lich-Gregoire onlay technique in a ten-step surgical video. RESULTS: Step 1: closure of the caudal ureter.Step 2: Ureter mobilization. Step 3: Ureter spatulation. Step 4: Bladder mobilization. Step 5: Detrusor muscle incision. Step 6: Bladder suspension. Step 7: Mucosal incision. Step 8: Ureterovesical anastomosis. Step 9: JJ stent insertion. Step 10: Detrusor muscle closure. CONCLUSION: Intraoperative identification of ureteral injury and prompt repair are recommended. Ureteral repair technique depends on the ureteral injury site. Distal ureteral injuries (UIs) might require either uretero-ureterostomy or ureteral reimplant with or without a psoas hitch. The Lich-Gregoir is one of the two most frequently used anti-vesicoureteral reflux techniques and has acceptable complication rates.

A New Paradigm in Managing Advanced Ovarian Cancer: Differentiating Patients Requiring Neoadjuvant Treatment from Primary Cytoreduction.

Our study aims to evaluate the comparability of primary debulking surgery (PDS) and neoadjuvant chemotherapy (NACT) patients. This single-center retrospective study includes all patients treated for advanced stages high-grade serous ovarian carcinomas (HGSOC) between 2007 and 2017. Preoperative characteristics and postoperative outcomes were compared after a propensity score matching analysis. Of the 221 patients included, 38% underwent PDS, and 62% received NACT. There was no age difference at diagnosis; however, CA125 levels, PCI score levels, and rates of stage IV were higher in the NACT group. There were no differences concerning the rate and the severity of complications (p = 0.29). The propensity score distribution showed a broad distinction between PDS patients and NACT patients with no significant overlap. Survival analyses demonstrate, after a median follow-up of 66.5 months, an overall survival (OS) of 105.9 and progression-free survival (PFS) of 29.2 months in the PDS group, compared to OS of 52.8 and PFS of 18.9 months in the NACT group. Advanced HGSOC is a heterogeneous population, in which inoperable patients should be differentiated from PDS patients based on many factors, primarily tumor burden.

Subspecialty training in Europe: a report by the European Network of Young Gynaecological Oncologists.

BACKGROUND: ESGO (European Society of Gynaecological Oncology) and partners are continually improving the developmental opportunities for gynaecological oncology fellows. The objectives of this survey were to evaluate the progress in the infrastructure of the training systems in Europe over the past decade. We also evaluated training and assessment techniques, the perceived relevance of ENYGO (European Network of Young Gynaecological Oncologists) initiatives, and unmet needs of trainees. METHODOLOGY: National representatives of ENYGO from 39 countries were contacted with an electronic survey. A graduation in well/moderately/loosely-structured training systems was performed. Descriptive statistical analysis and frequency tables, as well as two-sided Fisher's exact test, were used. RESULTS: National representatives from 33 countries answered our survey questionnaire, yielding a response rate of 85%. A national fellowship is offered in 22 countries (66.7%). A logbook to document progress during training is mandatory in 24 (72.7%) countries. A logbook of experience is only utilized in a minority of nations (18%) for assessment purposes. In 42.4% of countries, objective assessments are recognized. Trainees in most countries (22 (66.7%)) requested additional training in advanced laparoscopic surgery. 13 (39.4%) countries have a loosely-structured training system, 11 (33.3%) a moderately-structured training system, and 9 (27.3%) a well-structured training system. CONCLUSION: Since the last publication in 2011, ENYGO was able to implement new activities, workshops, and online education to support training of gynaecological oncology fellows, which were all rated by the respondents as highly useful. This survey also reveals the limitations in establishing more accredited centers, centralized cancer care, and the lack of laparoscopic training.

Outcomes of the use of different vulvar flaps for reconstruction during surgery for vulvar cancer.

BACKGROUND: Vulvar carcinoma is a rare cancer, accounting for 3-5% of all gynecological cancers. Surgery is the standard treatment for patients with early stage vulvar cancer and vulvar reconstruction can be performed for these patients. The present study aimed to compare three different flap and to analyze the outcomes of vulvar surgery. METHODS: We performed a single-center retrospective study between October 2001 and December 2015. We compare patients who underwent radical surgery for vulvar cancer combined with three different vulvar flap reconstructions (GTF, gluteal thigh flap; RF, rhomboid flap; VYF, V-Y flap). We collected data on the operating time, length of hospital stay, reoperation rate, and postoperative complications. RESULTS: We reviewed 179 patients who underwent radical vulvar surgery and 61 (34%) of these underwent additional reconstruction. There were no significant differences in clinical characteristics between the three groups. The median hospital stay was significantly longer for the GTF group (24 days) than RF (17 days) and than VYF (14 days) (p = 0.002). No significant differences were found concerning the operating time. Regarding postoperative complications, reoperation rates of 69%, 41%, and 25% were noted in the GTF, RF, and VYF group, respectively (p = 0.04); partial necrosis was the most common postoperative complication. The overall and recurrence-free survivals were comparable between the three groups. CONCLUSION: When the defect is too large, VYF seems to be the procedure of choice for ensuring healing without a prolonged hospital stay compared to RF and GTF. Moreover, VYF was associated with a lower reoperation rate within 60 days compared to RF and GTF.