Valentina Chiappa

Delivery delay with neoadjuvant chemotherapy for cervical cancer patients during pregnancy: A series of nine cases and literature review

OBJECTIVE Treatment of locally invasive cervical cancer diagnosed during pregnancy in women who desire to retain their pregnancy is a major challenge to physicians. Neoadjuvant chemotherapy followed by radical hysterectomy has been reported to be an attractive option to delay delivery until fetal viability has been reached. METHODS Between 1994 and 2009 9 patients were treated at San Gerardo Hospital (Monza, Italy) for cervical cancer during pregnancy. RESULTS FIGO stage was IB1 in four patients and IB2 in five. Tumor diameter ranged between 20 and 70 mm. After neoadjuvant platinum-based chemotherapy partial response was achieved in 5 patients, while 4 had a stable disease. One patient received a second-line chemotherapy during pregnancy due to progressive disease, achieving a partial response. Median duration of therapy delay until cesarean section was 16 weeks. Between 30 and 36 weeks of gestation all patients underwent cesarean section. Piver II radical hysterectomy with pelvic lymphadenectomy was performed. Two children had mild perinatal morbidities and were discharged in good conditions after 14 and 40 days. Three patients received adjuvant therapy for pathological risk factors. Four patients relapsed (44%) and two of them (23%) died because of tumor progression. CONCLUSION During pregnancy, the oncological outcome of cervical cancer patients is similar to non-pregnant ones. Chemotherapy does not seem to affect fetal health and development, even if longer follow-up is required. Therefore, neoadjuvant chemotherapy for the treatment of locally invasive cervical cancer during pregnancy seems to be a reasonable option for delay definitive treatment until fetal viability is obtained.

Adjuvant chemotherapy in stage I–II uterine leiomyosarcoma: A multicentric retrospective study of 140 patients

OBJECTIVE About 50-60% of patients with stage I-II uterine leiomyosarcoma (ULMS), primarily treated with surgery, relapse and die from progressive disease. In this retrospective study we describe the impact of adjuvant chemotherapy in this subset of patients. METHODS 140 women treated from 1976 to 2011 were included in the study. Univariate and multivariate analysis were used to test the association of clinical features and adjuvant treatments with overall survival (OS) and disease-free survival (DFS). RESULTS 62 women did not receive any further treatment after hysterectomy, 14 had radiotherapy (RT), 52 chemotherapy and 12 chemo-radiotherapy. Chemotherapy based on doxorubicin and ifosfamide combination was used in 54 cases. After a median follow-up of 63months, 87 women (62%) have relapsed, and 62 (44%) have died. The vast majority of patients who relapsed had distant recurrences (72%). The 5year median DFS and OS were 43% and 64% respectively. After 5years of follow up 68.7% of women treated with chemotherapy (±RT) vs 65.6% of patients only observed were alive (p=0.521). In the univariate analysis no factors had a statistical impact on DFS, while number of mitosis (>20×10HPF), age (>60years) and adjuvant radiotherapy were found as negative prognostic factors for OS. In the multivariate analysis only mitosis and age remained significant for OS. CONCLUSION Adjuvant chemotherapy was not associated with a significant survival benefit and should not be considered as standard of care for patients with stage I-II ULMS until randomized clinical studies will give further information.

Harmonic scalpel versus conventional electrosurgery in the treatment of vulvar cancer

To compare differences in blood loss, operative time, and intra‐ and postoperative complications with the harmonic scalpel or conventional electrosurgery in the treatment of vulvar cancer.

Efficacy of adjuvant chemotherapy in early stage uterine leiomyosarcoma: A systematic review and meta-analysis

OBJECTIVE We sought to review the current evidence in order to test the efficacy of adjuvant chemotherapy in improving disease-free survival in patients affected by early stage uterine leiomyosarcoma. METHODS On July 2016, literature was searched in order to identify trials comparing different postoperative adjuvant strategies for patients diagnosed with early stage uterine leiomyosarcoma. RESULTS Our analysis included 360 patients: 145 (40%), 53 (15%), and 155 (43%) had chemotherapy (with or without radiotherapy), radiotherapy, and observation, respectively. Seven (2%) patients who had radiotherapy with or without chemotherapy were excluded from further analysis in order to reduce risk of biases. Administration of chemotherapy (with or without radiotherapy) did not improve outcomes in comparison to observation (OR: 0.79 (95%CI: 0.48, 1.29)), or radiotherapy (OR: 0.90 (95%CI: 0.42, 1.94)). Loco-regional recurrence rate was similar comparing patients undergoing chemotherapy (with or without radiotherapy) with having observation alone (OR: 0.84 (95%CI: 0.44, 1.60)). Similarly, pooled results suggested that chemotherapy administration did not affect distant recurrence rate in comparison to no chemotherapy (OR: 0.80 (95%CI: 0.50, 1.28)), and observation alone (OR: 0.99 (95%CI: 0.60, 1.64)). However, patients undergoing chemotherapy (with or without radiotherapy) experienced a trend towards lower risk of developing distant recurrences (OR: 0.49 (95%CI: 0.24, 1.03)) and a higher risk of developing loco-regional recurrences (OR: 3.45 (95%CI: 1.02, 11.73)) than patients undergoing radiotherapy. CONCLUSIONS In early stage uterine leiomyosarcoma, the role of adjuvant chemotherapy remains unclear. Owing to the high recurrence rate, even in the early stage of disease, further innovative therapeutic strategies have to be tested.

How often parametrial involvement leads to post-operative adjuvant treatment in locally advanced cervical cancer after neoadjuvant chemotherapy and type C radical hysterectomy?

OBJECTIVE Parametrial involvement (PMI) is one of the most important factors influencing prognosis in locally advanced stage cervical cancer (LACC) patients. We aimed to evaluate PMI rate among LACC patients undergoing neoadjuvant chemotherapy (NACT), thus evaluating the utility of parametrectomy in tailor adjuvant treatments. METHODS Retrospective evaluation of consecutive 275 patients affected by LACC (IB2-IIB), undergoing NACT followed by type C/class III radical hysterectomy. Basic descriptive statistics, univariate and multivariate analyses were applied in order to identify factors predicting PMI. Survival outcomes were assessed using Kaplan-Meier and Cox models. RESULTS PMI was detected in 37 (13%) patients: it was associated with vaginal involvement, lymph node positivity and both in 10 (4%), 5 (2%) and 12 (4%) patients, respectively; while PMI alone was observed in only 10 (4%) patients. Among this latter group, adjuvant treatment was delivered in 3 (1%) patients on the basis of pure PMI; while the remaining patients had other characteristics driving adjuvant treatment. Considering factors predicting PMI we observed that only suboptimal pathological responses (OR: 1.11; 95% CI: 1.01, 1.22) and vaginal involvement (OR: 1.29 (95%) CI: 1.17, 1.44) were independently associated with PMI. PMI did not correlate with survival (HR: 2.0; 95% CI: 0.82, 4.89); while clinical response to NACT (HR: 3.35; 95% CI: 1.59, 7.04), vaginal involvement (HR: 2.38; 95% CI: 1.12, 5.02) and lymph nodes positivity (HR: 3.47; 95% CI: 1.62, 7.41), independently correlated with worse survival outcomes. CONCLUSIONS Our data suggest that PMI had a limited role on the choice to administer adjuvant treatment, thus supporting the potential embrace of less radical surgery in LACC patients undergoing NACT. Further prospective studies are warranted.

Incorporating 3D laparoscopy for the management of locally advanced cervical cancer: a comparison with open surgery.

Purpose To test the effects of the implementation of 3D laparoscopic technology for the execution of nerve-sparing radical hysterectomy. Methods Thirty patients undergoing nerve-sparing radical hysterectomy via 3D laparoscopic (3D-LNSRH, n = 10) or open surgery (NSRH, n = 20) were studied prospectively. Results No significant differences were observed in baseline patient characteristics. Operative times were similar between groups. We compared the first 10 patients undergoing 3D-LNSRH with the last 20 patients undergoing NSRH. Baseline characteristics were similar between groups (p>0.2). Patients undergoing 3D-LNSRH had longer operative time (264.4 ± 21.5 vs 217.2 ± 41.0 minutes; p = 0.005), lower blood loss (53.4 ± 26.1 vs 177.7 ± 96.0 mL; p<0.001), and shorter length of hospital stay (4.3 ± 1.2 vs 5.4 ± 0.7 days; p = 0.03) in comparison to patients undergoing open abdominal procedures. No intraoperative complication occurred. One (10%) patient had conversion to open surgery due to technical difficulties and the inability to insert the uterine manipulator. A trend towards higher complication (grade 2 or worse) rate was observed for patients undergoing NSRH in comparison to 3D-LNSRH (p = 0.06). Considering only severe complications (grade 3 or worse), no difference was observed (0/10 vs 2/20; p = 0.54). Conclusions 3D-laparoscopic nerve-sparing radical hysterectomy is a safe and effective procedure. The implementation of 3D laparoscopic technology allows the execution of challenging operations via minimally invasive surgery, thus reducing open abdominal procedure rates. Further large prospective studies are warranted.

Treatment of Recurrent Endometrial Carcinoma: Progress Toward a More Personalized Approach

TO THE EDITOR: The article by Slomovitz et al addresses an important and compelling clinical question regarding the treatment of recurrent endometrial cancer (EC). In their investigation, the authors provided further evidence for the safety profile and effectiveness of mammalian target of rapamycin (ie, everolimus) and aromatase inhibitors (ie, letrozole) for treating patients affected by progressive or recurrent EC. The authors reported important information regarding this combined therapy, thus seeding larger prospective investigations. They observed that the administration of everolimus plus letrozole correlates with encouraging response rates and survival outcomes, especially when compared with other therapeutic strategies. Of interest, one of the most important findings of the study is that serous histology is the strongest factor predicting nonresponse. However, two points regarding the treatment of recurrent EC deserve to be addressed: First, although the authors reported a complete analysis of the tumor specimens (reporting analyses on genes mutations), it should be interesting to evaluate the effect of this combined treatment in high-grade endometrioid EC. In fact, growing evidence questions the Bokhman’s dualistic model and supports that high-grade endometrioid EC much more closely resembles nonendometrioid type 2 cancer than endometrioid EC. By this point of view, we can speculate that in grade 1 and 2 endometrioid EC, everolimus plus letrozole may possibly provide more pronounced survival results in comparison with grade 3 and serous tumors. Moreover, the advantage of the combined treatment over both single strategies should be carefully evaluated in a risk-benefit ratio, given that indirect comparison of response rates in trials reporting activity of single-agent aromatase inhibitors or mammalian target of rapamycin inhibitors seems to show that they are roughly superimposable on the rates obtained with the combination at the price of reduced toxicity. Second, although the majority of patients affected by progressive or recurrent EC have systemic disease, we believe that, in selected cases, both exenterative and nonexenterative surgical procedures play an important role in locoregional control, thus improving progression-free and overall survival, especially in those patients suffering late recurrences. It would be extremely interesting to know the opinion of the authors on these issues. To us, in absence of clear evidence suggesting the more efficient treatment for recurrent EC, a personalized treatment is advocated. Novel therapies are needed for patients affected by high-grade and nonendometrioid EC.

The association of pre-treatment HPV subtypes with recurrence of VIN

OBJECTIVE To assess whether pre-treatment HPV types are associated with recurrence of high-grade vulvar intraepithelial neoplasia (VIN2+). STUDY DESIGN Data of consecutive patients with pretreatment HPV DNA test undergoing treatment for VIN2+ were retrospectively collected. Risk factors promoting the risk of VIN2+ persistence and recurrence were analyzed using Kaplan-Meier and Cox hazard proportional models. RESULTS 64 patients had pretreatment vulvar-vaginal HPV DNA test. Two were excluded due to the presence of synchronous vulvar cancer, thus leaving 62 patients for the final analysis. HPV16, HPV18, HPV31 and HPV33 were the most common HPV genotype detected, occurring in 15 (24.2%), 4 (6.5%), 8 (12.9%) and 5 (8.0%) patients, respectively. HPV was not detected in 19 (30.6%) patients. During a mean (SD) follow up of 56.7 (±26.7) months, 10 (16.1%) patients had VIN2+ persistence/recurrence. Mean (SD) lesion-free interval was 51.7 (±31.4) months. Via multivariate analysis, pretreatment infection from HPV31 (HR:46.7(95%CI:4.21,518.4); p=0.02) and HPV33 (HR:77.0(95%CI:6.73,881.9); p<0.001) correlated with an increased risk of VIN2+ persistence/recurrence. Additionally, we observed that patients undergoing surgical excision followed by LASER ablation experienced a trend towards lower recurrence rate than patients undergoing other surgical or medical treatments (HR:0.20(95%CI:0.03,1.09); p=0.05). Two (3.2%) patients developed progression to vulvar cancer. CONCLUSIONS Owing to the inherent biases of the retrospective study design and the small sample size, our data have to be corroborated by larger and prospective studies. HPV31 and HPV33 have a potential role in predicting VIN2+ persistence/recurrence. These findings will be paramount, owing to the implementation of new immunization programs.

Human papillomavirus (HPV) persistence and HPV 31 predict the risk of recurrence in high-grade vaginal intraepithelial neoplasia

OBJECTIVE High-grade vaginal intraepithelial neoplasia (vaginal HSIL) represents an uncommon entity. Here, we sought to identify predictors for recurrence and risk factor for developing genital cancers after primary treatment for vaginal HSIL. METHODS Data of consecutive 5104 women who had human papillomavirus (HPV) DNA test were searched for identify women with histological confirmed vaginal HSIL. Disease-free interval and the risk of developing HPV-related gynecological cancers were assessed using Kaplan-Meier and Cox proportional hazard models. RESULTS Overall, 77 patients were included. After a mean (SD) follow-up of 69.3 (33.0) months, 11 (14%) and 4 (5%) patients experienced vaginal HSIL recurrence and the occurrence of HPV-related gynecological cancers, respectively. Via multivariate analysis factors predicting for vaginal HSIL recurrence were infection from HPV31 at diagnosis (HR: 5.0 (95%CI:1.17, 21.3); p=0.03) and persistence of HPV infection after treatment (HR: 7.0 (95%CI:1.54, 31.6); p=0.01). Additionally, patients who had LASER ablation experienced a trend toward a lower risk of recurrence in comparison to medical treatment (HR: 0.20 (95%CI:0.03, 1.09); p=0.06). Considering the occurrence of HPV-related gynecological cancers, we observed that no factors independently correlated with this risk; while, a trend towards higher risk was observed for women with HIV infection (HR:16.4 (95%CI:0.90, 300.1); p=0.06) and persistence of HPV infection (HR: 13.3 (95%CI:0.76, 230.2); p=0.07). CONCLUSIONS Patients affected by vaginal HSIL experienced a relatively high risk of recurrence. Persistence of HPV after treatment and pretreatment HPV-31 infection predicts for high-grade vaginal intraepithelial neoplasia recurrence. Further investigations are warranted in order to corroborate our data.

Agreement of two-dimensional and three-dimensional transvaginal ultrasound with magnetic resonance imaging in assessment of parametrial infiltration in cervical cancer

To compare two‐dimensional (2D) and three‐dimensional (3D) transvaginal ultrasound with magnetic resonance imaging (MRI) as the gold standard in assessment of parametrial infiltration of cervical cancer and to determine if all parts of the cervix are equally assessable with ultrasound.