Reproductive outcomes after conservative treatment in early and advanced stage MOGCTs.

BACKGROUND: Malignant ovarian germ cell tumors usually occur in young women. The standard of care is fertility sparing surgery and comprehensive surgical staging followed by adjuvant chemotherapy with BEP (bleomycin, etoposide, cisplatin) if needed. The aim of this study was to analyze the reproductive outcomes after conservative treatment in patients diagnosed, treated and followed up in MITO (Multicenter Italian Trials in Ovarian Cancer) centers. METHODS: A questionnaire concerning gynecological symptoms, reproductive outcomes and fertility treatment was administered to 164 MOGCTs survivors. Data regarding patients deceased were collected from MITO-9 database. There were 114 patients diagnosed at reproductive age between 1983 and 2019 included. RESULTS: 109 patients answered the questionnaire and 5 patients decesased were included (median age 24.9 years). 78.1% were stage I,4.4% stage II, 14.9% stage III and 2.6% stage IV. 57.9% received chemotherapy, the mean number of cycles was 4.1. Median time to menstrual recovery after BEP was of 5.6 months range, only 1 case of premature ovarian failure was reported. Among the 114 patients 38 (33.3%) attempted to become pregnant, 29/38 (76.3%) got pregnant with a total of 44 conceptions. 40.9% received chemotherapy and 22.9% did not (p 0.048). Pregnancy desire was the only predictive factor associated with live births among women who attempted pregnancy after treatment. CONCLUSIONS: As MOGCTs affect women of child-bearing age, fertility preservation represents a major treatment issue. Our results are consistent with the available evidence, confirming that adjuvant chemotherapy for MOGCT does not impact the reproductive function and fertility.

Surveillance alone in stage I malignant ovarian germ cell tumors: a MITO (Multicenter Italian Trials in Ovarian cancer) prospective observational study.

OBJECTIVE: The aim of this study was to analyze the oncological outcome of stage I malignant ovarian germ cell tumors patients included in the MITO-9 study to identify those who might be recommended routine surveillance alone after complete surgical staging. METHODS: MITO-9 was a prospective observational study analyzing data collected between January 2013 and December 2019. Three groups were identified: group A included 13 patients stage IA dysgerminoma and IAG1 immature teratoma; group B included 29 patients with stage IB-C dysgerminomas, IA-C G2-G3 immature teratomas and stage IA mixed malignant ovarian germ cell tumors and yolk sac tumors; and group C included five patients (two patients with stage IC1 and one patient with stage IC2 yolk sac tumors and two patients with mixed-stage IC2 malignant ovarian germ cell tumors). RESULTS: A total of 47 patients with stage I conservatively treated malignant ovarian germ cell tumors were analyzed. Two patients in group B were excluded from the routine surveillance alone group due to positive surgical restaging. Therefore, a total of 45 patients were included in the study. Median follow-up was 46.2 months (range; 6-83). In total, 14 of 45 patients (31.1%) received chemotherapy, while 31 (68.9%%) underwent surveillance alone. One patient in group A, with stage IA dysgerminoma had a relapse, successfully managed with conservative surgery and chemotherapy. None of the patients in group B and C relapsed. All patients were alive at completion of the study. Overall, among 31 patients (68.9%) who underwent surveillance alone, only one patient relapsed but was treated successfully. CONCLUSIONS: Our data showed that close surveillance alone could be an alternative option to avoid adjuvant chemotherapy in properly staged IB-C dysgerminomas, IA-IC G2-G3 immature teratomas, and IA mixed malignant ovarian germ cell tumors with yolk sac tumor component.

Validation of the AJCC prognostic stage for HER2-positive breast cancer in the ShortHER trial.

BACKGROUND: The 8th edition of the American Joint Committee on Cancer (AJCC) staging has introduced prognostic stage based on anatomic stage combined with biologic factors. We aimed to validate the prognostic stage in HER2-positive breast cancer patients enrolled in the ShortHER trial. METHODS: The ShortHER trial randomized 1253 HER2-positive patients to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy. Patients were classified according to the anatomic and the prognostic stage. Distant disease-free survival (DDFS) was calculated from randomization to distant relapse or death. RESULTS: A total of 1244 patients were included. Compared to anatomic stage, the prognostic stage downstaged 41.6% (n = 517) of patients to a more favorable stage category. Five-year DDFS based on anatomic stage was as follows: IA 96.6%, IB 94.1%, IIA 92.4%, IIB 87.3%, IIIA 81.3%, IIIC 70.5% (P < 0.001). Five-year DDFS according to prognostic stage was as follows: IA 95.7%, IB 91.4%, IIA 86.9%, IIB 85.0%, IIIA 77.6%, IIIC 67.7% (P < 0.001). The C index was similar (0.69209 and 0.69249, P = 0.975). Within anatomic stage I, the outcome was similar for patients treated with 9 weeks or 1 year trastuzumab (5-year DDFS 96.2% and 96.6%, P = 0.856). Within prognostic stage I, the outcome was numerically worse for patients treated with 9 weeks trastuzumab (5-year DDFS 93.7% and 96.3%, P = 0.080). CONCLUSIONS: The prognostic stage downstaged 41.6% of patients, while maintaining a similar prognostic performance as the anatomic stage. The prognostic stage is valuable in counseling patients and may serve as reference for a clinical trial design. Our data do not support prognostic stage as guidance to de-escalate treatment. TRIAL REGISTRATION: EUDRACT number: 2007-004326-25; NCI ClinicalTrials.gov number: NCT00629278.

Does methotrexate (MTX) dosing in a 8-day MTX/FA regimen for the treatment of low-risk gestational trophoblastic neoplasia affect outcomes? The MITO-9 study.

OBJECTIVE: To compare clinical outcomes of patients diagnosed with low-risk gestational trophoblastic neoplasia (GTN) receiving intramuscular methotrexate 50 mg total dose/day versus 1 mg/kg/day in a 8-day methotrexate/folinic acid (MTX/FA) regimen. METHODS: This retrospective, multicenter study included 176 patients: 99 (56%) receiving methotrexate 50 mg total dose/day on days 1, 3, 5, 7 alternated with FA 7,5 mg on days 2, 4, 6, 8, every 14 days (group A); and 77 patients (44%), receiving methotrexate 1 mg/kg/day on days 1, 3, 5, 7 alternated with FA 7,5 mg on days 2, 4, 6, 8, every 14 days (group B). Patients' characteristics and outcomes were compared by univariate analysis. RESULTS: Forty-five patients (25.6%) developed resistance to MTX and received a second-line treatment, 7 (4%) received a third-line treatment and 8 (4.5%) relapsed after initial remission. There was no difference between group A and B patients in the average number of chemotherapy cycles required to achieve remission (5.7 ±â€¯2.6 vs 6.3 ±â€¯2.3, p = 0.106). The 2 treatment groups showed comparable rates of MTX resistance (28.3% vs 22.1%, p = 0.387) and relapse (3% vs 6.5%, p = 0.300). There was no difference in the incidence of treatment toxicity of any CTCAE grade between group A and B patients (16.2% vs 15.2%, p = 0.999). Subgroup analysis stratifying patients by weight (<50 kg, ≥60 kg, ≥70 kg, ≥80 kg) confirmed these results. CONCLUSION: The 2 MTX schedules showed comparable efficacy in the treatment of low-risk GTN with an acceptable rate of toxicity.

Laparoscopic Nerve-Preserving Sacropexy.

STUDY OBJECTIVE: To demonstrate our developed nerve-preserving technique during laparoscopic sacropexy (LSP) for multicompartment pelvic organ prolapse. DESIGN: A step-by-step demonstration of our surgical procedure on video (Canadian Task Force classification II-2). Informed consent was obtained from the subject, and the applicable Institutional Review Board provided approval. SETTING: Although sacropexy does remain the 'gold standard' procedure for apical prolapse [1], the subjective outcome of the procedure has been reported to be not so satisfactory as its anatomic outcome [2]. New onset bowel symptoms have been observed with voiding and sexual dysfunctions [3]. Published data revealed a correlation between iatrogenic denervation during LSP and postoperative dysfunctions [4-6]. We adopted a nerve-preserving approach with the aim of reducing the iatrogenic morbidity. INTERVENTIONS: Our surgical nerve-preserving LSP technique from the promontory down to the right uterosacral ligament and the rectovaginal space proceeds in 3 steps: Step 1: Opening the peritoneum. The peritoneum is opened just medial to the right common iliac artery, approximately 20 to 30 mm above the sacral promontory, allowing a safe approach in an area far from nerves and vascular structures. Peritoneal incision is extended toward the promontory. The underlying presacral fascia containing the right hypogastric nerve (rHN) is identified and incised longitudinally. The presacral fascia and the rHN are then pushed medially to expose the longitudinal anterior vertebral ligament; the finding of the middle sacral veins represents the limit of any further medial dissection. Opening and displacement of the prevertebral fascia are not mandatory. Step 2: Opening the peritoneum of the right pelvic sidewall, respecting the integrity of the presacral fascia and of the rHN contained within it. An inverted L-shaped peritoneal incision extending from the sacral promontory up to the left uterosacral ligament is completed, with care taken to preserve the rHN identified previously. In proximity to the uterus, the dissection line crosses the upper edge of the right uterosacral ligament at its proximal third and extends medially. The rectovaginal space is opened and joined to the peritoneal tunnel with a section of the superficial layer of the right uterosacral ligament, preserving its deep nervous portion. Step 3: Dissection of the rectovaginal space, respecting the integrity of the rectal fascia. The rectovaginal space is fully dissected, and at its caudal edge the dissection is carried out laterally to the rectum upward to identify the pelvic parietal fascia covering the levator ani muscle, in the middle to the cranial edge of the perineal body. Preservation of the rectal fascia prevents possible injury to the middle rectal vessels and the rectal branches of the inferior hypogastric plexus, which runs close to the pelvic floor. The complete dissection of the rectovaginal space appears in an inverted V-shaped space covering approximately two-thirds of the posterior vaginal wall, with the apex at the convergence of the uterosacral ligaments. The procedure is completed with dissection of the vesicovaginal space through the creation of an avascular triangular-shaped space with the apex at the dorsal end of the bladder trigone and laterally limited by the superficial vascular layer of the vesicouterine ligaments. The bladder branches of the inferior hypogastric plexus run far from the surgical field in the deep portion of the vesicouterine ligaments. CONCLUSION: A nerve-sparing approach to pelvic spaces during LSP is feasible following well-defined surgical steps, which allow the surgeon to visualize all of the nerve pathways and potentially dangerous anatomic structures.

5-Fluorouracil, epirubicin and cyclophosphamide versus epirubicin and paclitaxel in node-positive early breast cancer: a phase-III randomized GONO-MIG5 trial.

The study was designed to compare an anthracycline-containing regimen to a regimen combining both anthracycline and paclitaxel as adjuvant therapy for high-risk breast cancer patients. In this multicenter, randomized phase-III trial, node-positive early breast cancer patients were randomly assigned to receive either 6 cycles of FEC (5-fluorouracil 600 mg/m(2), epirubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2), day 1, every 3 weeks) or 4 cycles of EP (epirubicin 90 mg/m(2) and paclitaxel 175 mg/m(2), day 1, every 3 weeks). The primary endpoint was overall survival (OS). Secondary endpoints included toxicity and event-free survival (EFS). From 1996 to 2001, 1055 patients were enrolled. At a median follow-up of 12.8 years, 335 deaths had been recorded. The 10-year OS was 73 % (95 % CI 69-77) in the FEC arm and 74 % (95 % CI 70-78) in the EP arm (p = 0.405). The 10-year EFS was 51 % (95 % CI 45-56) in the FEC arm and 49 % (95 % CI 44-55) in the EP arm (p = 0.572). No difference in the hazard of death was observed (HR for EP 0.85, 95 % CI 0.68-1.06, p = 0.15). Patients treated with FEC experienced more frequently nausea and vomiting, stomatitis, and leukopenia as compared to patients treated with EP. Toxicities which occurred more frequently with EP were anemia, fever, myalgias, and neurotoxicity. Our study failed to demonstrate a superiority of an adjuvant treatment with four EP as compared to six FEC in node-positive breast cancer patients.

Accuracy of a new diagnostic tool in deep infiltrating endometriosis: Positron emission tomography-computed tomography with 16α-[18F]fluoro-17ß-estradiol.

AIM: Preoperative workup of deep infiltrating endometriosis is limited in the evaluation of extragenital and extrapelvic disease and in distinguishing between the previous surgical scar and active lesion. Histological verification remains the gold standard for diagnosis. The aim of this study was therefore to evaluate positron emission tomography-computed tomography (PET/CT) with an experimental estrogen receptor tracer (16α-[18F]fluoro-17ß-estradiol; [18F]FES) for accurate staging and non-invasive diagnosis of the disease. The primary endpoint was the feasibility of this tool on comparison with histology. The secondary endpoint was the accuracy of PET/CT in comparison with magnetic resonance imaging (MRI). METHODS: Four eligible subjects with extragenital endometriosis underwent MRI, PET/CT with [18F]FES, and laparoscopic excision of endometriosis in the same month. Region-by-region analysis was used to compare the findings of the two diagnostic tools with surgical histological specimens obtained during laparoscopy. RESULTS: A total of 40 anatomical regions were examined: seven were [18F]FES positive, four were positive on MRI and eight positive on histology. A total of nine regions were discordant. PET/CT agreed with histology in 9/9 of the discrepant findings. CONCLUSION: PET/CT with [18F]FES was feasible and had greater accuracy than MRI, particularly in patients with previous surgery. Further studies are needed, however, to investigate its role in bowel endometriosis in sites other than recto-sigmoid junction, nerve localization, and subcentimetric disease.

The "Sandwich" Schedule: A Well-Tolerated Adjuvant Treatment Both in Intermediate-High- and High-Risk Endometrial Cancer.

(1) Background: In intermediate-high- and high-risk endometrial cancer (EC), radiotherapy (RT) and chemotherapy (CT) play a basic role. However, there is controversy regarding the optimal timing of their combination. The "sandwich" schedule involves adjuvant CT followed by RT and subsequent CT. The aim of this study is to assess the tolerability and efficacy of the "sandwich" schedule. (2) Methods: A retrospective study was conducted in two gynecological oncology units in Torino, Italy, from 1 January 2003 until 31 December 2021. Intermediate-high- and high-risk patients with available clinical data were included. Compliance with treatment, CT and RT toxicities, disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS) were analyzed. (3) Results: A total of 118 patients were selected: 27.1% FIGO I-II stages and 72.9% III-IV. Most of the patients (75.4%) received a carboplatin-paclitaxel combination, and as much as 94.9% of CT cycles were completed. Chemotherapy-related G3-4 toxicities were detected in 5.3% of the patients, almost half of which were hematological. Grade 2 gastrointestinal and genitourinary toxicities were reported in 8.4% and 4.2% of cases, respectively. With a median follow-up of 46 months, DFS was 77.6%, CSS was 70% and 5-year OS was 54%. (4) Conclusions: The "sandwich" schedule for CT and RT combination is an effective adjuvant treatment with low toxicity both in intermediate-high- and high-risk EC.

Risk of unexpected uterine leiomyosarcoma during laparoscopic procedures: Experience from a single tertiary institute in Italy.

OBJECTIVE: To evaluate the incidence of occult uterine sarcomas and investigate whether an accurate and well-established preoperative assessment for uterine fibroids could help identify uterine sarcomas more effectively. METHODS: A retrospective analysis of patients who underwent gynecological laparoscopic surgery for presumed uterine fibroids at Sant'Anna Hospital, a single tertiary institute in Turin, Italy, between January 2003 and December 2019. RESULTS: Over the 17-year period, 5826 laparoscopic surgical procedures (myomectomies or subtotal/total hysterectomies) were performed for presumed uterine fibroids. A total of 48 patients with a final diagnosis of uterine sarcoma were identified, the majority of which (n = 39; 81.3%) were recognized as suspicious uterine sarcomas during the preoperative assessment, and morcellement was avoided. The occurrence of unexpected uterine sarcomas was 0.1% (6/5826). Morcellation was conducted in one patient with uterine sarcoma. CONCLUSION: Analysis of our data showed that unexpected uterine sarcomas are uncommon. Accurate preoperative evaluation can help avoid, but does not exclude, the possibility of morcellation of unknown uterine sarcomas.

Oncophone20 study: Patients' perception of telemedicine in the COVID-19 pandemic during follow-up visits for gynecological and breast cancers.

OBJECTIVE: To analyze oncological patients' perception of telemedicine during the COVID-19 pandemic. METHODS: A total of 345 women, of whom 267 experienced breast cancer and 78 experienced a gynecological cancer, were enrolled. Specific questionnaires about their experiences and feelings about telemedicine in the COVID-19 era were collected. RESULTS: In the breast group, "enhanced care" showed moderate positive perception (mean 4.40) among less-educated women that was slightly lower among better-educated women (mean 4.14) with a significant difference (P = 0.034). "satisfaction" had an opposite pattern: a mean of 3.99 for a lower level of education and 4.78 for a higher level of education, with a strong significant difference (P < 0.001). "privacy and discomfort" approached neutrality for less-educated women, while for higher-educated women the lower mean of 2.93 indicted a more positive perception (P = 0.007). In the pelvic group, younger women had a better perception towards telemedicine for "telemedicine as a substitution" (mean 3.68) compared to older women (mean 3.05). The privacy and discomfort subscale was in favor of better-educated women (mean 2.57) compared to less-educated women (mean 3.28; P = 0.042). CONCLUSION: Telemedicine was generally well accepted, not only among younger and higher-educated women but also by women needing intensive care, in both cancer groups.

Obstetric outcomes in patients who have undergone excisional treatment for high-grade cervical squamous intra-epithelial neoplasia.

OBJECTIVE: To evaluate the relationships between excisional treatment for high-grade cervical intra-epithelial neoplasia (CIN2+) and obstetric outcomes in terms of preterm delivery risk, premature rupture of membrane (PROM) and type of delivery, and between pre-term delivery and the type of excisional technique (radio frequency excision, laser conization). METHODS: This was a retrospective study of the obstetric outcomes of 2316 women aged 25-45 years who underwent excisional treatment for CIN2+ at the Obstetric and Gynecological Clinic of Ospedale Maggiore della Carità in Novara and at the Obstetric and Gynecological Department of Ospedale Sant'Anna in Torino in the period 2005-2014 and were evaluated until April 2016, and 57,937 untreated women of the same age, from the same centers. RESULTS: After treatment, 320 women had at least one pregnancy leading to delivery after a mean of 3.35 years. Treatment significantly increased the risk of preterm delivery. Compared with no treatment, the risk of preterm birth was higher in women who had undergone treatment (33.13% vs. 6.60%). Techniques removing or ablating more tissue, such as large loop excision of the transformation zone, were associated with worse outcomes (OR 2.96, 95% IC 1.72-5.10). Smoking habits significantly increase the risk of preterm delivery in the treated women (OR 2.82, 95% IC 1.61-4.9). The risk of premature rupture of the membranes (PROM) (40% vs. 23.22%), the risk of preterm PROM (pPROM) (13.13% vs. 2.71%) and dystocic births (18.75% vs 4.48%) were also significantly increased after treatment. Caesarean sections were less frequent among the treated women (15.94% vs. 32.41%). CONCLUSIONS: Our findings reveal a relationship between cervical excisional treatment and pre-term delivery, PROM, and the method of delivery. In order to minimise risk and guarantee the best obstetric outcome, patient treatment and follow-up should be personalised.

Axillary Dissection vs. no Axillary Dissection in Breast Cancer Patients With Positive Sentinel Lymph Node: A Single Institution Experience.

BACKGROUND/AIM: Axillary surgery of breast cancer patients is undergoing a paradigm shift, as axillary lymph node dissection's (ALND) usefulness is being questioned in the treatment of patients with tumor-positive sentinel lymph node biopsy (SLNB). The aim of this study was to investigate the overall survival (OS) and relapse-free survival (RFS) of patients with positive SLNB treated with ALND or not. PATIENTS AND METHODS: We investigated 617 consecutive patients with cN0 operable breast cancer with positive SLNB undergoing mastectomy or conservative surgery. A total of 406 patients underwent ALND and 211 were managed expectantly. RESULTS: No significant difference in OS and RFS was found between the two groups. The incidence of loco-regional recurrence in the SLNB-only group and the ALND group was low and not significant. CONCLUSION: The type of breast cancer surgery and the omission of ALND does not improve OS or RSF rate in cases with metastatic SLN.

Retrospective evaluation of clinical outcomes in patients with HER2-positive advanced breast cancer progressing on trastuzumab-based therapy in the pre-lapatinib era.

BACKGROUND: Patients with HER2-positive breast cancer whose disease has become resistant to the anti-HER2 monoclonal antibody trastuzumab can benefit from lapatinib, a dual epidermal growth factor receptor/HER2 tyrosine kinase (TK) inhibitor. Before the availability of this compound, trastuzumab was often continued beyond disease progression, usually in addition to further chemotherapy, an approach which was not based on randomized studies. We sought to retrospectively compare the clinical outcomes of patients who, upon progression during an initial trastuzumab-based regimen, stopped or continued trastuzumab in addition to further chemotherapy. PATIENTS AND METHODS: From the clinical records of 407 patients with HER2-positive advanced breast cancer, we identified 279 patients progressing during an initial trastuzumab-based treatment. Of these patients, 83 continued trastuzumab in addition to chemotherapy, and 112 received chemotherapy alone. RESULTS: We found no difference in response rate (28% vs. 30%; P = .5), median time to second tumor progression (8.4 months vs. 7 months; P = .24), or median postprogression survival (20.6 months and 15.4 months; P = .29) according to whether patients continued or stopped trastuzumab. At multivariate analysis, continuation of trastuzumab was associated with a statistically insignificant trend toward reduced risk of second progression (hazard ratio, 0.753; P = .08). CONCLUSION: Patients with HER2-positive advanced breast cancer developing tumor progression during an initial trastuzumab-based regimen did not seem to benefit significantly from the continuation of trastuzumab in addition to chemotherapy. For these patients, there is evidence from a large randomized trial that effective HER2 targeting can be accomplished by inhibiting the HER2 TK activity with lapatinib.

Simplified laparoscopic sacropexy avoiding deep vaginal dissection.

OBJECTIVE: To evaluate the safety and efficacy of a "simplified" laparoscopic sacropexy approach. METHODS: Data were retrospectively assessed from women with apical prolapse of stage 2 or higher who underwent "simplified" laparoscopic sacropexy between October 1, 2010, and May 31, 2017 at the St Anna Hospital, City of Health and Science, Torino, Italy. Patients were treated with the "simplified" laparoscopic sacropexy, where meshes were anchored solely to the vaginal apex, even in the presence of advanced multi-compartment vaginal prolapse. Data on prolapse stage and urogenital functions collected through clinical examinations, and questionnaires at baseline, 6 months, 12 months, and annually thereafter were examined. RESULTS: Overall, 121 women were included in the analysis; the mean follow-up was 33.2 months. Mean operative time was 135.1 minutes; there were no intraoperative visceral or vascular injuries. There was 1 (0.8%) patient who experienced recurrence, and 2 (1.7%) who experienced vaginal erosion. Both urogenital symptom scores (all P<0.05) and quality of life scores (all P<0.05) improved significantly. CONCLUSION: Adequate re-suspension of only the apex was sufficient to correct other vaginal compartments, even for women with preoperative multi-compartment prolapse higher than POP-Q stage 2. The "simplified" laparoscopic sacropexy was an efficacious intraoperative time-saving technique; it could reduce adverse events caused by deep vaginal dissection up to puborectal muscles and the bladder trigone.

Nerve preserving vs standard laparoscopic sacropexy: Postoperative bowel function.

AIM: To compare our developed nerve preserving technique with the non-nerve preserving one in terms of de novo bowel symptoms. METHODS: Patients affected by symptomatic apical prolapse, admitted to our department and treated by nerve preserving laparoscopic sacropexy (LSP) between October, 2010 and April, 2013 (Group A or "interventional group") were compared to those treated with the standard LSP, between September, 2007 and December, 2009 (Group B or "control group"). Functional and anatomical data were recorded prospectively at the first clinical review, at 1, 6 mo, and every postsurgical year. Questionnaires were filled in by the patients at each follow-up clinical evaluation. RESULTS: Forty-three women were enrolled, 25/43 were treated by our nerve preserving technique and 18/43 by the standard one. The data from the interventional group were collected at a similar follow-up (> 18 mo) as those collected for the control group. No cases of de novo bowel dysfunction were observed in group A against 4 cases in group B (P = 0.02). Obstructed defecation syndrome (ODS) was highlighted by an increase in specific questionnaires scores and documented by the anorectal manometry. There were no cases of de novo constipation in the two groups. No major intraoperative complications were reported for our technique and it took no longer than the standard procedure. Apical recurrence and late complications were comparable in the two groups. CONCLUSION: Our nerve preserving technique seems superior in terms of prevention of de novo bowel dysfunction compared to the standard one and had no major intraoperative complications.

Residual neurotoxicity in ovarian cancer patients in clinical remission after first-line chemotherapy with carboplatin and paclitaxel: the Multicenter Italian Trial in Ovarian cancer (MITO-4) retrospective study.

BACKGROUND: Carboplatin/paclitaxel is the chemotherapy of choice for advanced ovarian cancer, both in first line and in platinum-sensitive recurrence. Although a significant proportion of patients have some neurotoxicity during treatment, the long-term outcome of chemotherapy-induced neuropathy has been scantly studied. We retrospectively assessed the prevalence of residual neuropathy in a cohort of patients in clinical remission after first-line carboplatin/paclitaxel for advanced ovarian cancer. METHODS: 120 patients have been included in this study (101 participating in a multicentre phase III trial evaluating the efficacy of consolidation treatment with topotecan, and 19 treated at the National Cancer Institute of Naples after the end of the trial). All patients received carboplatin (AUC 5) plus paclitaxel (175 mg/m2) every 3 weeks for 6 cycles, completing treatment between 1998 and 2003. Data were collected between May and September 2004. Residual sensory and motor neurotoxicity were coded according to the National Cancer Institute--Common Toxicity Criteria. RESULTS: 55 patients (46%) did not experience any grade of neurological toxicity during chemotherapy and of these none had signs of neuropathy during follow-up. The other 65 patients (54%) had chemotherapy-induced neurotoxicity during treatment and follow-up data are available for 60 of them. Fourteen out of 60 patients (23%) referred residual neuropathy at the most recent follow-up visit, after a median follow up of 18 months (range, 7-58 months): 12 patients had grade 1 and 2 patients grade 2 peripheral sensory neuropathy; 3 patients also had grade 1 motor neuropathy. The remaining 46/60 patients (77%) had no residual neuropathy at the moment of interview: recovery from neurotoxicity had occurred in the first 2 months after the end of chemotherapy in 22 (37%), between 2 and 6 months in 15 (25%), or after more than 6 months in 9 patients (15%). Considering all 120 treated patients, there was a 15% probability of persistent neurological toxicity 6 months after the end of chemotherapy. CONCLUSION: A significant proportion of patients with advanced ovarian cancer treated with first-line carboplatin/paclitaxel suffer long-term residual neuropathy. This issue should be carefully taken into account before considering re-treatment with the same agents in sensitive recurrent disease.

Time to progression in metastatic breast cancer patients treated with epirubicin is not improved by the addition of either cisplatin or lonidamine: final results of a phase III study with a factorial design.

PURPOSE: To investigate the value of the addition of either cisplatin (CDDP) or lonidamine (LND) to epirubicin (EPI) in the first-line treatment of advanced breast cancer. PATIENTS AND METHODS: Three hundred seventy-one metastatic breast cancer patients with no prior systemic chemotherapy for advanced disease were randomized to receive either EPI alone (60 mg/m(2) on days 1 and 2 every 21 days), EPI and CDDP (30 mg/m(2) on days 1 and 2 every 21 days), EPI and LND (450 mg orally daily, given continuously), or EPI, CDDP, and LND. Time to progression, response rates, side effects, and survival were compared according to the 2 x 2 factorial design of this study. RESULTS: The groups were well balanced with respect to prognostic factors. Time to progression did not differ in the comparison between CDDP arms and non-CDDP arms (median, 10.9 months v 9.4 months, respectively; P =.10) or between that of LND arms and non-LND arms (median, 10.8 months v 9.9 months, respectively; P =.47), nor did overall survival. The response rate did not significantly differ in the comparison between LND arms and non-LND arms (62.9% v 54.0%, P =.08). No difference in treatment activity was observed between CDDP arms and non-CDDP arms. Toxicity was significantly higher in the CDDP arms, leading to CDDP dose adjustment in 40% of cases. The most frequent side effects were of a hematologic and gastrointestinal nature. The addition of LND produced more myalgias and fatigue. CONCLUSION: Neither CDDP nor LND was able to significantly improve the time to progression obtained by EPI. CDDP, however, significantly worsened the drug's tolerability.

Topotecan compared with no therapy after response to surgery and carboplatin/paclitaxel in patients with ovarian cancer: Multicenter Italian Trials in Ovarian Cancer (MITO-1) randomized study.

PURPOSE: Topotecan is an active second-line treatment for advanced ovarian cancer. Its efficacy as consolidation treatment after first-line standard chemotherapy is unknown. PATIENTS AND METHODS: To investigate whether topotecan (1.5 mg/m(2) on days 1 through 5, four cycles, every 3 weeks) prolonged progression-free survival (PFS) for patients responding to standard carboplatin (area under the curve 5) and paclitaxel (175 mg/m(2) administered as a 3-hour infusion in six cycles; CP), a multicenter phase III study was performed with an 80% power to detect a 50% prolongation of median PFS. Patients were registered at diagnosis and randomized after the end of CP. RESULTS: Two hundred seventy-three patients were randomly assigned (topotecan, n = 137; observation, n = 136), with a median age of 56 years. Stage at diagnosis was advanced in three fourths of patients (stage III in 65% of patients; stage IV in 10%); after primary surgery, 46% had no residual disease and 20% were optimally debulked. After CP, 87% reached a clinical complete response, and 13% achieved a partial response. Neutropenia (grade 3/4 in 58% of the patients) and thrombocytopenia (grade 3 in 21%; grade 4 in 3%) were the most frequent toxicities attributed to topotecan. There was no statistically significant difference in PFS between the arms (P =.83; log-rank test): median PFS was 18.2 months in the topotecan arm and 28.4 in the control arm. Hazard ratio of progression for patients receiving topotecan was 1.18 (95% CI, 0.86 to 1.63) after adjustment for residual disease, interval debulking surgery, and response to CP. CONCLUSION: The present analysis indicates that consolidation with topotecan does not improve PFS for patients with advanced ovarian cancer who respond to initial chemotherapy with carboplatin and paclitaxel.

Combination regimen of epirubicin, vinorelbine and 5-fluorouracil continuous infusion as first-line chemotherapy in anthracycline-naive metastatic breast cancer patients.

We investigated the activity and toxicity of a combination of vinorelbine 25 mg/m2 on days 1 and 15; epirubicin 25 mg/m2 on days 1, 8, 15; and 5-fluorouracil continuous infusion at 200 mg/m2 every day, administered as first-line chemotherapy in anthracycline-naive metastatic breast cancer patients. Fifty-three patients entered the study. Cycles were repeated every 28 days. Objective response was 60% by World Health Organisation (WHO) criteria and 63% by Response Evaluation Criteria in Solid Tumours (RECIST). The median time to progression was 12.7 months (17.6 months in responders) and the median survival duration was 32.9 months. The dose-limiting toxicity was leucopenia (grade 3/4 in 36% of patients). Grade 3/4 non-haematological toxicities included mucositis in 11% of patients, skin and cardiac toxicity in 4% and 2%, respectively. The combination of vinorelbine, epirubicin and 5-fluorouracil continuous infusion was found to be an active and manageable first-line regimen for metastatic breast cancer patients.