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Background/Aim: The role of neoadjuvant chemotherapy (NACT) is under investigation in locally advanced cervical cancer (LACC). Patients and Methods: A total of 49 patients with FIGO stage IB1-IIB cervical cancer who underwent two different regimens of weekly dose-dense NACT were included. The objective was to evaluate clinical/pathological response and toxicity profile. Results: A clinical complete response and partial response were obtained in 43 patients with a clinical overall response rate of 88%. Among the 42 surgically treated patients, 7 (17%) and 35 (83%) achieved a pathological overall optimal response and a suboptimal pathological response, respectively. G3-G4 neutropenia occurred in 16% of patients, whereas no cases of G3 thrombocytopenia, G3 anemia and febrile neutropenia were observed. Conclusion: Dose-dense NACT is safe, has acceptable toxicity, and obtains good clinical response, but is less effective in terms of pathological overall optimal response rates compared to other regimens.

Background/Aim: To assess response rates and survival in patients with recurrent platinum-sensitive epithelial ovarian cancer (EOC) who received PARP inhibitor (PARP-i) maintenance and who subsequently underwent salvage chemotherapy for disease progression after PARPi. Patients and Methods: This retrospective investigation analyzed 103 patients who were treated in five Italian Gynecologic centers. The PARPi used was olaparib in 46 patients, niraparib in 55, and rucaparib in 2. The interval time between the last cycle of pre- PARPi platinum–based chemotherapy and the diagnosis of progression during PARPi maintenance was defined as platinum–free interval (PFI). Results: Of the 28 patients with PFI [removed]12 months received chemotherapy (platinum-based chemotherapy, 23; trabectedin + PLD, 3; non platinum – single agent, 5). An objective response was found in 13.0%, 26.2% and 41.9 % of the patients with PFI [removed]12 months (p= 0.03), respectively, and the corresponding median survivals after PARPi were 8.9 months, 17.5 months and 24.1 months (p= 0.002), respectively. Conclusion: Before the PARPi era, some randomized trials on platinum rechallenge in patients with recurrent EOC after more than 6 months from the last platinum cycle have shown response rates ranging from 47.2% to 66%. Response rates to chemotherapy for progression after PARPi appear to be lower than those expected according to PFI.

Background/Aim: The aim of the study was to assess the outcome of advanced ovarian cancer patients who i) underwent primary surgery followed by carboplatin/paclitaxel-based chemotherapy with or without bevacizumab, ii) were in complete response after chemotherapy, iii) and subsequently recurred. Patients and Methods: The hospital records of 138 complete responders after chemotherapy with (n=58) or without (n=80) bevacizumab were reviewed. Results: Both survival after recurrence and overall survival were related to age (=61 vs. >61 years, p=0.002 and p=0.0001), performance status (0 vs. =1, p=0.002 and p=0.001), histotype (serous vs. non serous, p=0.005 and p=0.01), time to recurrence (=12 vs. <12 months, p<0.0001 and p<0.0001) and treatment at recurrence (surgery plus chemotherapy vs. chemotherapy, p=0.01 and p=0.004), but not to first-line treatment. Conclusion: This investigation failed to detect a more aggressive behavior of recurrent ovarian cancer after bevacizumab-containing primary treatment.

Background/Aim: The aim of the study was to assess the clinical outcome of patients with malignant transformation of an ovarian mature teratoma. Patients and Methods: This study was conducted on 23 patients who underwent primary surgery at three Italian Gynecological Centers. Histologically, nine (39.1%) patients had squamous cell carcinoma, five (21.7%) had a thyroid carcinoma, six (26.1%) had a carcinoid, one (4.3%) patient had papillary renal carcinoma, one (4.3%) had medulloblastoma and one (4.3%) had intestinal-type mucinous adenocarcinoma. Results: All six patients with stage I squamous cell carcinoma had no evidence of disease (NED) after a median time of 141 months. Of the three patients with stage IIb-IIIc squamous cell carcinoma, two had NED after 119 and 154 months, and one died of the disease 9 months after diagnosis. All five women with stage I thyroid carcinoma had NED after a median of 60 months. Of the six patients with stage I carcinoid, five had NED after a median of 168 months, whereas one died due to carcinoid heart disease. The three patients with stage I renal carcinoma, medulloblastoma and mucinous adenocarcinoma had NED after 24, 141 and 149 months, respectively. Conclusion: The clinical outcome of early-stage malignancies associated with mature ovarian teratomas is excellent following treatment.

Aim: To assess the patterns of recurrence and clinical outcomes of patients with cervical adenocarcinoma who underwent neoadjuvant platinum-based chemotherapy (NACT) followed by radical hysterectomy. Patients and Methods: Data were retrospectively analyzed for 82 patients with International Federation of Gynecology and Obstetrics stage Ib2-IIb cervical adenocarcinoma who underwent this chemo-surgical treatment. The median follow-up of survivors was 89 months (range=5-208 months). Results: Pathological complete response, optimal response and suboptimal response with intra-cervical residual disease were obtained in five (6%), 10 (12%) and 36 (44%) patients, respectively. Adjuvant external-beam radiotherapy with or without concurrent chemotherapy was administered to 47 patients. Nineteen (23%) out of the 82 patients experienced recurrence after a median of 12 months (range=5.3-86.8 months). Recurrent disease was pelvic in 12 (63%) patients, extra-pelvic in five (26%), and both pelvic and extra-pelvic in two (10%). According to pathological response, tumor relapsed in 10% of optimal responders, 14% of sub-optimal responders with intra-cervical residual disease, and 36% of sub-optimal responders with extra-cervical residual disease or non-responders. Five-year recurrence-free and overall survival were 77% and 84%, respectively. Patients who achieved an optimal response or sub-optimal response with intra-cervical residual disease had better 5-year recurrence-free (87% vs. 64%, p=0.017) and overall (92% vs. 74%, p=0.012) survival than those who had sub-optimal response with extra-cervical residual disease or no response. The latter had a 1.441-fold higher risk of recurrence and a 1.652-fold higher risk of death than those who obtained an optimal response or a sub-optimal response with intra-cervical residual disease. Conclusion: NACT followed by radical hysterectomy may be an option for patients with stage Ib2-IIb adenocarcinoma of the uterine cervix

Objectives The purpose of this retrospective study was to assess the clinical outcome of patients with high-risk, early-stage endometrioid endometrial cancer (stage Ib or II with myometrial invasion > 50%, grade 2-3). Methods We assessed 192 patients who underwent hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy, had histologically negative pelvic nodes, and had negative CT findings for aortic node involvement. Results Tumor relapsed in 36 patients after a median time of 21.2 months. The recurrence was vaginal in 7 (19.4%), distant in 16 (44.4%), aortic in 8 (22.2%), and involved multiple sites in 5 (13.9%). There was a trend to a lower vaginal recurrence rate in the 143 patients who received adjuvant radiotherapy (+ chemotherapy) compared with the 46 who did not (2.1% versus 8.7%). Distant or aortic recurrences were lower in the 37 patients who received adjuvant chemotherapy (+ radiotherapy) than in the 152 who did not (2.7% versus 18.4%, p = 0.02). Of the 29 patients who received sequential adjuvant chemotherapy and radiotherapy, none developed local recurrence and only one had distant recurrence. There was a trend for a better 5-year progression-free survival and overall survival for the patients who received chemotherapy (+ radiotherapy) compared with those who did not (86.0% versus 71.3%, and 92.3% versus 75.6%, respectively). Conclusions Our data appear to suggest that adjuvant chemotherapy reduces the risk of distant or aortic recurrences and that sequential adjuvant chemotherapy and radiotherapy achieve an excellent local and distant control of disease in these clinical settings. © 2014 Published by Elsevier Inc.

Purpose Neoadjuvant chemotherapy [NACT] followed by radical hysterectomy is an alternative therapeutic option to concurrent chemotherapy-radiotherapy for locally advanced cervical cancer. However there are very few data about the effectiveness of any post-operative treatment in this clinical setting. The purpose of this study was to correlate the patterns of recurrence and the clinical outcomes of cervical cancer patients who received NACT, with postoperative adjuvant treatment. Patients and methods This retrospective multicenter study included 333 patients with FIGO stage Ib2-IIb cervical cancer who underwent platinum-based NACT followed by radical surgery. Pathological responses were retrospectively assessed as complete; optimal partial; and suboptimal response. Overall optimal response rate was the sum of complete and optimal partial response rates. Results On the whole series, recurrence-free survival was significantly longer in patients who achieved an overall optimal response than in those who did not (p < 0.0001), and in patients who received adjuvant chemotherapy compared to those who did not (p = 0.0001). On multivariate analysis, consolidation therapy (p = 0.0012) was the only independent prognostic variable for recurrence-free survival; whereas FIGO stage (p = 0.0169) and consolidation therapy (p = 0.0016) were independent prognostic variables for overall survival. Conclusion Optimal responders after chemo-surgical treatment for FIGO stage Ib2-IIb cervical cancer do not need any further treatment. Additional cycles of chemotherapy could be of benefit for patients with suboptimal response and intra-cervical residual disease. Both adjuvant chemotherapy and adjuvant radiation treatments do not seem to improve the clinical outcome of patients with extra-cervical residual disease compared to no further treatment. © 2014 Elsevier Inc.

Objectives The purpose of this retrospective multicenter study was to correlate patterns of recurrences and clinical outcome of cervical cancer patients who underwent neoadjuvant chemotherapy [NACT] to surgery. Methods This study was conducted on 333 patients with FIGO stage Ib2-IIb cervical cancer who underwent NACT to surgery with pelvic lymphadenectomy. The median follow-up was 66.5 months (range, 8-212 months). Overall optimal response rate was the sum of complete and optimal partial response rates. Results An overall optimal response was obtained in 64 patients (19.2%). As for the 220 sub-optimal responders (66.1%), 127 patients had negative nodes and negative parametria and/or surgical margins, 75 patients had positive nodes with positive or negative parametria and/or surgical margins, and 18 patients had positive parametria and/or surgical margins with negative nodes. At the time of the present analysis, 79 (23.7%) of the 333 patients had a recurrence after a median time of 14.9 months (range, 4.5-123 months). Recurrent disease was pelvic in 50 (63.3%), extra-pelvic in 22 (27.9%), and both in 7 (8.8%). On multivariate analysis, pathological response to NACT was an independent prognostic variable for recurrence-free and overall survival. Patients who did not achieve an overall optimal response had a 2.757-fold higher risk of recurrence and a 5.413-fold higher risk of death than those who obtained an overall optimal response. Conclusions Results appear to suggest that the chemo-surgical approach is an effective therapeutic option for patients with stage Ib2-IIb cervical cancer and that pathological response to NACT is the strongest prognostic factor for the outcome. © 2013 Elsevier Inc.

Objective: To assess the pattern of failures and the survival of patients with uterine papillary serous carcinoma (UPSC). Methods: The hospital records of 119 women with UPSC were reviewed. Surgery was the initial therapy for all the cases. The median follow-up of survivors was 133 months (range, 3Y216 months). Results: Postoperative treatment was used in 98 patients (82.4%). Adjuvant treatment was radiotherapy in 25 women, chemotherapy in 61 women, and chemotherapy plus radiotherapy in 12 women. Tumor recurred in 44 (37.0%) of the 119 patients, after a median time of 15.1 months. Relapse was symptomatic in 15 patients (34.1%), and recurrent disease involved peritoneum or distant sites in 26 (66.7%) of the 39 patients for whom the site of failure was known. Five- and 10-year survival rates were 61.8% and 54.6%, respectively. Survival was related to disease stage (P G 0.0001). Among patients with advanced tumor, 5-year survival was lower in women who had macroscopic residual disease after surgery than in those who had not (15.4% vs 37.5%; P = 0.08). Distant failures were higher in women with histologically proven positive nodes than in those with negative nodes (28.6% vs 9.1%; P = 0.048). There was a trend to better survival for patients with stage I to stage II disease who underwent chemotherapy when compared with those who did not. Conclusions: Uterine papillary serous carcinoma has an aggressive clinical behavior with a great tendency to recur especially in peritoneal and distant sites. Tumor stage is a strong prognostic factor, whereas the role of adjuvant treatment is still uncertain. © 2012 by IGCS and ESGO.

The aim of this retrospective investigation was to assess the pattern of failures of 412 patients with recurrent ovarian cancer followed up with different surveillance protocols.Time to recurrence was less than 6 months in 98 women (23.8%), 6 to 12 months in 102 women (24.7%), and more than 12 months in 212 women (51.5%). Symptoms at relapse were referred by 81 women (19.7%). Among the 331 asymptomatic patients, the surveillance procedure that raised the suspect of recurrent disease was clinical examination in 49 (14.8%), imaging technique in 90 (27.2%), serum CA 125 in 77 (23.3%), and both serum CA 125 and imaging technique in 115 (34.7%). At univariate analysis, survival from initial diagnosis was related to stage (P = 0.004), residual disease after initial surgery (P < 0.0001), time to recurrence (P < 0.0001), site of relapse (P = 0.04), and treatment at recurrence (P < 0.0001), and survival after recurrence was related to stage (P = 0.01), residual disease (P < 0.0001), time to recurrence (P < 0.0001), and treatment at recurrence (P < 0.0001). Conversely, symptoms at recurrence had no prognostic relevance. Cox proportional hazards model showed that residual disease and time to recurrence were the only independent prognostic variables for both survival from initial diagnosis (P < 0.0001) and survival after recurrence (P < 0.0001). In conclusion, there was no survival difference between asymptomatic and symptomatic patients at the time of relapse, and therefore, the diagnostic anticipation allowed by a scheduled follow-up protocol did not seem to improve the clinical outcome of patients who ultimately developed recurrent disease.

This is a retrospective study of patients treated for early-stage cervical cancer to identify pathologic risk factors associated with ovarian metastases and, therefore, to establish when ovarian preservation can be performed without increasing the risk of relapse in order to improve the quality of life in premenopausal patients. Between 1982 and 2004, 1965 patients with FIGO stage IA2-IB-IIA cervical squamous cell carcinoma and nonsquamous histology types were surgically treated; 1695 (86%) patients underwent primary radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic node dissection, the remaining 270 patients (14%) had their ovaries preserved. The clinical records were reviewed for all patients and clinical features at presentation, the histopathology and follow-up data were recorded. Overall, ovarian metastases were diagnosed in 16 of 1695 patients, for an incidence rate of 0.9%. Univariate analysis shows age (≤45 vs >45 years: P = 0.0079), FIGO stage (IB1-IIA ≤4 cm vs IB2-IIA >4 cm: P = 0.0133), histology (squamous vs nonsquamous, P = 0.0014), noninvolved peripheral stromal thickness (<3 vs >3 mm: P = 0.0001), lymphvascular space involvement (present vs absent, P = 0.0007), lymph node status (positive vs negative, P = 0.00009) to be statistically associated with the presence of ovarian metastases. Multivariate analysis shows only age (P = 0.0119), FIGO stage (P = 0.011), histology (P = 0.001), and unaffected peripheral stromal thickness (<3 mm: P = 0.037) to be independent risk factors for ovarian metastases. Based on the present data and on the data available in the literature, ovarian preservation could be safely performed in young patients with early-stage squamous cell carcinoma (histology as the most significant risk factor), with macroscopically normal ovaries, and with preserved peripheral unaffected cervical stroma

Epithelial ovarian cancer is the leading cause of death from gynecological cancer in the Western countries. Approximately 20%-30% of patients with early-stage disease and 50%-75% of those with advanced disease who obtain a complete response following first-line chemotherapy will ultimately develop recurrent disease, which more frequently involves the pelvis and abdomen. Few formal guidelines exist regarding the surveillance of these patients, and there is no agreement in the literature about the type and timing of examinations to perform. Moreover, the objective of follow-up is unclear as recurrent epithelial ovarian cancer continues to be a therapeutic dilemma and quite all the relapsed patients will eventually die of their disease. The follow-up of asymptomatic patients generally include complete clinical history, serum cancer antigen (CA)125 assay, physical examination, and often ultrasound examination, whereas additional radiologic imaging techniques are usually performed when symptoms or signs appear. 18Fluoro-2-deoxy-glucose (18FDG)-positron emission tomography (PET) has a sensitivity of 90% and a specificity of 85% approximately for the detection of recurrent disease, and this examination appears to be particularly useful for the diagnosis of recurrence when CA125 levels are rising and conventional imaging is inconclusive or negative. Recently, technologic advances have led to novel combined 18FDG-PET/ computed tomography (CT) devices, which perform contemporaneous acquisition of both 18FDG-PET and CT images. The role of 18FDG-PET/CT for the detection of recurrent ovarian cancer is very promising, and this technique may be especially useful for the selection of patients with late recurrent disease who may benefit from secondary cytoreductive surgery

Purpose: To assess whether the interval from primary surgery to the start of taxane- plus platinum-based chemotherapy has any impact on the clinical outcome of advanced ovarian cancer patients. Patients and Methods: The study was conducted on 313 patients who underwent surgery followed by taxane- plus platinum-based chemotherapy. The median follow-up of survivors was 30.7 months (range, 6 to 109 months). Results: The 25%, 50%, and 75% quantiles of intervals from surgery to the start of chemotherapy were 11, 21, and 31 days, respectively. After the sixth cycle, 102 patients achieved a pathologic complete response at second-look surgery and 98 obtained a clinical complete response but were not submitted to second-look surgery. Taking into consideration the best assessed response, a complete (either clinical or pathologic) response was found in 200 patients. Residual disease (≤ 1 v > 1 cm; P < .0001) and ascites (absent v present; P = .003) were independent predictive factors for achieving a complete response, whereas residual disease (P = .001 ) and stage (IIc to III v IV; P = .04) were independent prognostic variables for survival. Conversely, statistical analyses failed to detect significant differences in complete response rates and survival among patients with an interval from surgery to chemotherapy shorter than 11 days, 12 to 21 days, 22 to 31 days, and longer than 31 days. Conclusion: The interval from surgery to the start of taxane- plus platinum-based chemotherapy seems to have neither a predictive value for response to treatment nor a prognostic relevance for survival of advanced ovarian cancer patients

Objective. The objective of this retrospective multicenter study was to assess the pattern of failures and survival of patients with primary carcinoma of the fallopian tube. Methods. The hospital records of 88 patients with primary carcinoma of the fallopian tube were reviewed. Surgery was the initial therapy for all patients. Tumor stage was I in 21 (23.9%), II in 21 (23.9%), III in 43 (48.8%), and IV in 3 (3.4%) patients. Postoperative treatment was given without well-defined protocols. The median follow-up of survivors was 55 months (range, 7-182). Results. Of the 21 patients with stage I disease, 10 had no postoperative treatment and 11 had platinum-based chemotherapy. Five (23.8%) patients recurred after a median of 29 months (range, 8-93) from initial surgery. Of the 21 patients with stage II disease, 2 had no postoperative treatment, 2 underwent external pelvic irradiation, 16 received platinum-based chemotherapy, and 1 patient had oral melphalan. Eight (38.1%) patients recurred after a median of 25.5 months (range, 7-57). Of the 46 patients with stage III-IV disease, 1 patient refused chemotherapy and died after 19 months and 45 patients received platinum-based chemotherapy. A clinical complete response was obtained in 29 (64.4%) patients and a partial response in 8 (17.8%). A second-look laparotomy was performed in 14 of the 29 clinically complete responders: 12 patients were found to be in pathological complete response and 2 had persistent disease. Six (50.0%) of the former recurred after a median of 22 months (range, 13-101) from initial surgery. The two patients with persistent disease developed tumor progression after 15 and 11 months, respectively. Fifteen clinically complete responders did not undergo second-look, and 7 (46.7%) of them had a recurrence after a median of 18 months (range, 9-41). For the whole series, 5-year survival was 57%. By log-rank test, survival was related to FIGO stage (III-IV vs I-II, P = 0.0001), tumor grade (G3 vs G1 + G2

This multicenter retrospective study is based on 192 patients with advanced ovarian cancer in pathological complete response at second-look surgery. Ninety-four (48.9%) patients developed recurrent disease after a median time of 18 months (range, 4-89 months) from surgical reassessment. The recurrence involved the pelvis in 45 (47.9%) cases, the abdomen in 42 (44.7%), the retroperitoneal lymph nodes in 13 (13.8%), and distant sites in 20 (21.2%). On the whole series, 5- and 7-year disease-free survival rates after negative second-look were 47.4 and 44.5%, respectively. By log-rank test the disease-free survival rate was related to FIGO stage (P = 0.008), tumor grade (P = 0.0021), size of residual disease after initial surgery (P = 0.0038), and type of second-look (laparoscopy vs laparotomy, P = 0.0061), but not to histological type and first-line chemotherapy. Cox proportional hazard model showed that tumor grade, size of residual disease, and type of second- look were independent prognostic variables for disease-free survival. The risk ratio of relapse was 2.386 (95% CI, 1.140-4.990) for grade 2 and 3.118 (95% CI, 1.515-6.416) for grade 3 compared to grade 1 disease. For patients with residual disease 1-2 cm and >2 cm the risk ratio was, respectively, 1.877 (95% CI, 1.117-3.156) and 2.156 (95% CI, 1.324-3.511) compared to patients with residual disease <1 cm. The risk ratio was 1.826 (95% CI, 1.121-2.973) for patients who were submitted to a laparoscopic second-look compared to those who underwent a laparotomic reassessment. Poorly differentiated grade and large residual disease after initial surgery are the strongest prognostic variables for recurrence after a negative second-look