3D fusion is superior to 2D point-to-point contrast-enhanced US to evaluate the ablative margin after RFA for hepatocellular carcinoma.

PURPOSE: To compare the efficiency of three-dimensional (3D) and two-dimensional (2D) contrast-enhanced ultrasound (CEUS)-derived techniques in evaluating the ablative margin (AM) after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). METHODS: In total, 98 patients with 98 HCCs were enrolled. The 2D CEUS point-to-point imaging (2D CEUS-PI) was conducted by comparing the pre- and post-RFA 2D CEUS images manually, and the 3D CEUS fusion imaging (3D CEUS-FI) was conducted by fusing the pre- and post-RFA 3D CEUS images automatically. These two techniques were compared in distinguishing an adequate AM ≥ 5 mm. Risk factors for local tumor progression (LTP) after RFA were analyzed by the Kaplan-Meier method with log-rank test. RESULTS: The mean registration time of 3D CEUS-FI and 2D CEUS-PI was 5.0 and 9.3 min, respectively (p < 0.0001). The kappa coefficient was 0.680 for agreement between 2D CEUS-PI and 3D CEUS-FI in the evaluation of AM (p < 0.0001). Tumors with AM < 5 mm by 2D CEUS-PI were all identified as AM < 5 mm by 3D CEUS-FI. Nonetheless, 16 (26%) tumors identified as AM ≥ 5 mm by 2D CEUS-PI were re-classified as AM < 5 mm by 3D CEUS-FI. During a median follow-up time of 31.2 months (range, 3.2-66.0 months), LTP was identified in 8 tumors. The estimated 1-/2-/3-year cumulative incidence of LTP was 4.4%, 8.1%, and 10.3%, respectively. Higher estimated cumulative incidence of LTP was identified in tumors with AM < 5 mm by 2D CEUS-PI (at 3-year, 27.2% vs 0%; p < 0.001), and by 3D CEUS-FI (at 3-year, 20.7% vs 0%; p = 0.004). CONCLUSION: 3D CEUS-FI excelled in the evaluation of AM when compared with 2D CEUS-PI. With equivalent efficacy in the prediction of LTP, 3D CEUS-FI was superior to 2D CEUS-PI for its automatic and time-saving procedure. CLINICAL RELEVANCE STATEMENT: 3D CEUS fusion imaging may serve as an effective tool in evaluating ablative margin and predicting local tumor progression after RFA in HCC. KEY POINTS: • Both 2D and 3D CEUS-derived techniques could evaluate ablative margin (AM) after RFA for hepatocellular carcinoma. • 3D CEUS fusion imaging was more precise in the evaluation of AM compared to 2D CEUS point-to-point imaging, with advantages of its automatic and time-saving procedure. • An inadequate AM < 5 mm evaluated by CEUS-derived techniques was the only risk factor of LTP after RFA for hepatocellular carcinoma (p < 0.001 for 2D CEUS point-to-point imaging, and p = 0.004 for 3D CEUS fusion imaging).

A randomized phase II study of secondary cytoreductive surgery in patients with relapsed ovarian cancer who have progressed on a PARP inhibitor as first-line maintenance therapy: the SOCCER-P study (KGOG 3067/JGOG 3036/APGOT-OV11).

BACKGROUND: Although two recent phase III randomized controlled trials showed survival benefits of undergoing secondary cytoreductive surgery for an initial relapse of ovarian cancer, patients who received a poly-ADP ribose polymerase inhibitor (PARPi) as the first-line maintenance treatment, which is currently the standard treatment for advanced ovarian cancer, were not included in those trials. Therefore, determining an optimal treatment strategy, including secondary cytoreductive surgery, in patients whose cancer progresses even with PARPi treatment, is needed. PRIMARY OBJECTIVE: To determine whether secondary cytoreductive surgery is beneficial in patients who have progressed on PARPi maintenance treatment. STUDY HYPOTHESIS: Secondary cytoreductive surgery followed by chemotherapy is superior to chemotherapy alone for patients who have progressed on PARPi maintenance treatment. TRIAL DESIGN: The SOCCER-P study is a multicenter randomized phase II clinical trial. Patients who meet the eligibility criteria will be randomized to either undergo secondary cytoreductive surgery and subsequent platinum-based chemotherapy plus or minus bevacizumab, or to receive platinum-based chemotherapy plus or minus bevacizumab alone. Patients randomly allocated to the surgery group will undergo secondary cytoreductive surgery followed by six cycles of a physician's choice of platinum-based chemotherapy once they have recovered from surgery. MAJOR INCLUSION/EXCLUSION CRITERIA: The major inclusion criteria are as follows: first recurrence of disease with treatment-free interval from last platinum dose (TFIp) ≥6 months and progression during PARPi maintenance or treatment-free interval from last PARPi therapy (TFIPARPi) <3 months. The major exclusion criteria are as follows: >1 line of prior chemotherapy, TFIp <6 months, and radiological signs suggesting metastases not accessible to surgical removal (complete resection is deemed not possible). PRIMARY ENDPOINT: Progression-free survival. SAMPLE SIZE: 124 patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual completion approximately the end of 2026 and the results are expected after 2 years of follow-up in 2029. TRIAL REGISTRATION: NCT05704621.

TRImodal DEfinitive invasive vagiNal carcinoma Treatment (TRIDENT protocol): how a standardized approach may change prognostic outcomes.

OBJECTIVE: Vaginal carcinoma is a rare malignancy accounting for 1-2% of all gynecological cancers. Surgery has a limited role, while definitive radiotherapy-chemotherapy followed by interventional radiotherapy is considered a valid alternative. The aim of the TRIDENT (TRImodal DEfinitive invasive vagiNal carcinoma Treatment) pilot study was to report the results of a modern standardized trimodal protocol treatment consisting of image guided definitive radiotherapy-chemotherapy followed by image guided interventional radiotherapy in terms of safety and efficacy. METHODS: Between January 2019 and December 2021, we analyzed 21 consecutive patients with primary vaginal cancer who had received radiotherapy-chemotherapy followed by interventional radiotherapy. The primary study endpoint was local control, and secondary endpoints were metastasis free survival, overall survival, and rate and severity of acute and late toxicities. RESULTS: 14 patients had FIGO (International Federation of Gynecology and Obstetrics) stage II, five patients had stage III, and two had stage IVB disease. Median total external beam radiotherapy dose for the tumor was 45 Gy. Median total dose on positive nodes was 60 Gy. Median total dose for interventional radiotherapy was 28 Gy over four high dose rate fractions to achieve between 85 and 95 Gy equivalent dose, in 2 Gy fractions (EQD2)α/ß10, to the high risk clinical target volume, and 60 Gy EQD2α/ß10 to the intermediate risk clinical target volume. All patients received weekly platinum based chemotherapy. Median follow-up was 20 months (range 10-56 months). Two year actuarial local control, metastasis free survival, and overall survival rate were 79.4%, 90.5%, and 79.4%, respectively. In terms of acute toxicity, there were no grade 4 events and only one acute grade (G) 3 toxicity (skin). Only vaginal stenosis (G3) was documented 12 months after therapy due to late toxicity. CONCLUSIONS: In this study, definitive radiotherapy-chemotherapy followed by interventional radiotherapy was a safe and effective treatment modality for primary vaginal cancer.

Optimizing patient selection for secondary cytoreductive surgery in recurrent endometrial cancer.

OBJECTIVE: This retrospective, multicenter, observational study aimed to refine patient selection criteria for secondary cytoreductive surgery in recurrent endometrial cancer. The objective was to identify preoperative predictors of complete cytoreduction, assess surgical complexity, and propose a preoperative predictive scoring system to identify suitable candidates for secondary cytoreductive surgery. METHODS: Data from 331 women with recurrent endometrial cancer were analyzed across three Italian centers from January 2010 to December 2021. Patients were categorized based on treatment received (medical treatment, diagnostic laparoscopy/examination under anesthesia, or secondary cytoreductive surgery). Preoperative predictors, surgical complexity, complications, and a predictive scoring system were assessed. Logistic regression and receiver operating characteristic analysis were used for statistical evaluation. RESULTS: Of the cohort, 56.2% underwent debulking surgery, 17.2% had diagnostic laparoscopy, and 26.6% received medical treatment. Patients undergoing secondary cytoreductive surgery were younger, with a lower body mass index, better performance status, and fewer comorbidities. Single site locoregional relapse was common in secondary cytoreductive surgery patients. Age <65 years, single site relapse, lymph node, and hematogenous relapse were independent predictors of complete cytoreduction. A predictive scoring system demonstrated a clear relationship between the score and the likelihood of complete cytoreduction. CONCLUSION: This study identified age <65 years, single site recurrence, as well as nodal and hematogenous recurrence, as predictive factors for achieving optimal cytoreduction. A predictive scoring system incorporating these factors has been proposed to identify optimal candidates for secondary cytoreductive surgery in recurrent endometrial cancer. The scoring system showed promising predictive accuracy and could aid in refining the decision making process, ensuring appropriate patient selection for secondary cytoreductive surgery. Further prospective studies are warranted to validate and enhance the predictive model.

Low-grade versus high-grade serous ovarian cancer: comparison of surgical outcomes after secondary cytoreductive surgery.

OBJECTIVE: Retrospective series have shown secondary cytoreductive surgery improves oncological outcomes in recurrent low-grade serous ovarian cancer. We aim to compare surgical procedures and complications between patients with low-grade and high-grade recurrent serous ovarian cancer. METHODS: This retrospective single-institution study includes patients with recurrent low-grade and high-grade serous ovarian cancer undergoing surgery between January 2012 to December 2021. Patients were propensity matched 1:3 for residual tumor at first surgery, presence of ascites and performance status. Complexity of surgery and postoperative complications were analyzed. RESULTS: A total of 116 patients undergoing secondary cytoreductive surgery were included with 29 patients (25%) having low-grade ovarian cancer. The median age of the patients was 54 years (range: 19-85) and 57 years (range: 29-78) in low-grade and high-grade ovarian cancer, respectively (p=0.13). Stages III/IV at diagnosis were more frequent in patients with high-grade ovarian cancers (p<0.001). Peritoneal involvement was higher in low-grade compared with high-grade ovarian cancer as shown by the higher rate of diaphragmatic (41.4% vs 21.8%, p=0.05), abdominal wall (41.4% vs 18.4%, p=0.02) and pelvic (51.7% vs 21.8%, p=0.01) peritonectomy. Multiple bowel resections were higher in low-grade ovarian cancer (24.1% vs 8.0%, p=0.04), while high-grade ovarian cancer had a higher rate of nodal recurrences (73.2%% vs 37.9%, p=0.03). Overall, surgical complexity was higher in low-grade ovarian cancer (58.6% vs 36.8%; p=0.05), with higher median estimated blood loss (400 vs 200 mL; p=0.01) compared with high-grade. Complete cytoreduction was achieved in 26 patients (89.7%) with low-grade and 84 (96.6%) with high-grade (p=0.16) ovarian cancer, with no significant differences in postoperative complications. CONCLUSIONS: Secondary cytoreductive surgery in low-grade serous ovarian cancer patients was associated with higher complexity, multiple bowel resections, and higher median estimated blood loss than in high-grade serous ovarian cancer. The comparable rate of postoperative complications suggests that secondary cytoreductive surgery in this group of patients is feasible in expert centers.

Circulating tumor DNA as a biomarker for predicting progression-free survival and overall survival in patients with epithelial ovarian cancer: a systematic review and meta-analysis.

OBJECTIVES: Circulating tumor DNA (ctDNA) is emerging as a potential prognostic biomarker in multiple tumor types. However, despite the many studies available on small series of patients with ovarian cancer, a recent systematic review and meta-analysis is lacking. The objective of this study was to determine the association of ctDNA with progression-free-survival and overall survival in patients with epithelial ovarian cancer. METHODS: An electronic search was conducted using PubMed (MEDLINE), Embase, CENTRAL (Cochrane Library), and CINAHL-Complete from January 2000 to September 15, 2023. To be included in the analysis the studies had to meet the following pre-specified inclusion criteria: (1) evaluable ctDNA; (2) progression-free-survival and overall survival reported as hazard ratio (HR); and (3) the patient population had epithelial ovarian cancer at the time of ctDNA detection. We evaluated the association of ctDNA with progression-free survival and overall survival. Secondary outcomes focused on sub-group analysis of genomic alterations and international Federation of Gynecology and Obstetrics (FIGO) stage. RESULTS: A total of 26 studies reporting on 1696 patients with epithelial ovarian cancer were included. The overall concordance rate between plasma-based and tissue-based analyses was approximately 62%. We found that a high level of ctDNA in epithelial ovarian cancer was associated with worse progression-free survival (HR 5.31, 95% CI 2.14 to 13.17, p<0.001) and overall survival (HR 2.98, 95% CI 1.86 to 4.76, p<0.0001). The sub-group analysis showed a greater than threefold increase in the risk of relapse in patients with positive HOXA9 meth-ctDNA (HR 3.84, 95% CI 1.57 to 9.41, p=0.003). CONCLUSIONS: ctDNA was significantly associated with worse progression-free survival and overall survival in patients with epithelial ovarian cancer. Further prospective studies are needed. PROSPERO REGISTRATION NUMBER: CRD42023469390.

Can "no-touch" radiofrequency ablation for hepatocellular carcinoma improve local tumor control? Systematic review and meta-analysis.

OBJECTIVES: Percutaneous radiofrequency ablation (RFA) is one of the curative treatments for hepatocellular carcinoma (HCC), but local tumor progression (LTP) has been a main limitation of RFA. This study aims to evaluate the LTP of percutaneous no-touch RFA (NtRFA) for HCC ≤ 5 cm and compare with conventional RFA (intratumoral puncture) through a systematic review and meta-analysis. METHODS: MEDLINE, EMBASE, and Cochrane Library were searched for studies on percutaneous NtRFA for HCC ≤ 5 cm. The pooled proportions of the overall and cumulative incidence rates at 1, 2, and 3 years for LTP after NtRFA were assessed using a random-effects model. For studies comparing NtRFA with conventional RFA, relative risks (RR) and hazard ratios (HR) were meta-analytically pooled with LTP as the outcome. RESULTS: Twelve studies with 900 patients were included. The pooled overall rate of LTP after NtRFA was 6% (95% CI, 4-8%). The pooled 1-, 2-, and 3-year cumulative incidence rates of LTP were 3% (95% CI, 2-5%), 5% (95% CI, 3- 9%), and 8% (95% CI, 6-11%), respectively. Compared to conventional RFA, the pooled RR and HR of LTP were 0.26 (95% CI, 0.16-0.41) and 0.28 (95% CI, 0.11-0.70), respectively (both p < 0.01). Subgroup analysis including only randomized controlled studies also showed better local tumor control of NtRFA with HR of 0.13 (95% CI, 0.14-0.42). CONCLUSIONS: Percutaneous NtRFA is an effective treatment for HCC ≤ 5 cm with an overall LTP rate of 6% and provides lower LTP compared with conventional RFA. KEY POINTS: • The pooled 1-, 2-, and 3-year cumulative incidence rates of local tumor progression after no-touch radiofrequency ablation for HCC ≤ 5 cm were 3% (95% CI, 2-5%), 5% (95% CI, 3-9%), and 8% (95% CI, 6-11%). • No-touch radiofrequency ablation had significantly lower rates of local tumor progression compared to conventional radiofrequency ablation (hazard ratio, 0.28; 95% CI, 0.11-0.70; relative risk, 0.26; 95% CI, 0.16-0.41; p < 0.01, respectively).

A multicenter comparative matched-pair analysis of percutaneous tumor ablation and robotic-assisted partial nephrectomy of T1b renal cell carcinoma (AblatT1b study-UroCCR 80).

OBJECTIVE: Renal cell carcinomas represent the sixth- and tenth-most frequently diagnosed cancer in men and women. Recently, percutaneous-guided thermal ablations have proved to be as effective as partial nephrectomy and safer for treating small renal masses (i.e., < 3 cm). This study compared the perioperative and recurrence outcomes of percutaneous thermal ablation (TA) and robotic-assisted partial nephrectomy (RAPN) for the treatment of T1b renal cell carcinomas (4.1-7 cm). METHODS: Retrospective data from 11 centers on the national database, between 2010 and 2020, included 81 patients treated with thermal ablation (TA) and 308 patients treated with RAPN for T1b renal cell carcinoma, collected retrospectively and matched for tumor size, histology results, and the RENAL score. TA included cryoablation and microwave ablation. Endpoints compared the rate between the two groups: local recurrence, metastases, complications, renal function decrease, and length of hospitalization. RESULTS: After matching, 75 patients were included in each group; mean age was 76.6 (± 9) in the TA group and 61.1 (± 12) in the RAPN group, including 69.3% and 76% men respectively. The local recurrence (LR) rate was significantly higher in the TA group than in the PN group (14.6% vs 4%; p = 0.02). The LR rate was 20% (1/5) after microwave ablation, 11.1% (1/9) after radiofrequency ablation, and 14.7% (9/61) after cryoablation. The major complication rate (Clavien-Dindo ≥ 3) was higher following PN than after TA (5.3% vs 0%; p < 0.001). Metastases, eGFR decrease, and length of hospitalization did not differ significantly between the two groups. CONCLUSIONS: The local recurrence rate was significantly higher after thermal ablation; however, thermal ablation resulted in significantly lower rates of complications. Thermal ablation and robotic-assisted partial nephrectomy are effective treatments for T1b renal cancer; however, the local recurrence rate was higher after thermal ablation. KEY POINTS: • The local recurrence rate was significantly higher in the thermal ablation group than in the partial nephrectomy group. • The major complication rate (Clavien-Dindo ≥ 3) was higher following PN than after TA (5.3% vs. 0%; p < 0.001).

Effect of BMI change on recurrence risk in patients with endometrial cancer.

OBJECTIVE: Our study aimed to explore the effect of body mass index (BMI) change on cancer recurrence risk during the routine surveillance of endometrial cancer patients. METHODS: Data on patients with endometrial adenocarcinoma that had a staging procedure and continued follow-up was retrospectively collected. We compared patients' BMI at time of surgery and during the last clinic follow-up. Univariate and multivariate analyses were performed to examine the effect of predictors on BMI change and the risk of recurrence. RESULTS: A total of 211 patients were included in the final analysis. The majority of patients had stage I disease (n=176, 89%) and endometrioid histology (n=178, 86%). Median follow-up time was 53.4 (standard deviation (SD) 40) months. The mean BMI was 30.4 kg/m2 (interquartile range (IQR) 25-34) at surgery compared with 30.9 kg/m2 (IQR 26-36) at last follow-up (p<0.001). The BMI increase was most pronounced in patients with endometroid histology that recurred, 31.6 (IQR 24-35) kg/m2 at surgery compared with 33.5 (IQR 27-36) kg/m2 at last follow-up (p=0.016). On multivariate analysis, age and BMI change were the only predictors that were significantly associated with the risk of recurrence (overall response (OR 1.07 (0.99-1.14), p=0.05, OR 1.37 (1.12-1.67), p=0.002, respectively). CONCLUSION: Patients with endometroid endometrial cancer that had an increase in BMI during follow-up were at an increased risk for cancer recurrence compared with patients that did not change or had a decrease in BMI.

Role of salvage radiotherapy for recurrent ovarian cancer.

OBJECTIVE: This study aimed to report clinical outcomes of salvage radiotherapy for recurrent ovarian cancer and identify predictors of clinical outcomes. METHODS: We retrospectively reviewed data of patients who received salvage radiotherapy for recurrent ovarian cancer between January 2011 and June 2021. Stereotactic body radiotherapy, involved-field radiotherapy with conventional fractionation, and non-involved-field radiotherapy with conventional fractionation were included in this study. Local failure-free survival, progression-free survival, chemotherapy-free survival, and overall survival were assessed. Additionally, potential prognostic factors for survival were analyzed. RESULTS: A total of 79 patients were included with 114 recurrent lesions. The median follow-up was 18.3 months (range 1.7-83). The 2-year local failure-free survival, progression-free survival, chemotherapy-free survival, and overall survival rates were 80.7%, 10.6%, 21.2%, and 74.7%, respectively. Pre-radiotherapy platinum resistance (hazard ratio (HR) 3.326, p<0.001) and short pre-radiotherapy CA-125 doubling time (HR 3.664, p<0.001) were associated with poor chemotherapy-free survival. The 1-year chemotherapy-free survival rates of patients with both risk factors, a single risk factor, and no risk factor were 0%, 20.4%, and 53.5%, respectively. The difference between risk groups was statistically significant: low risk versus intermediate risk (p<0.001) and intermediate risk versus high risk (p<0.001). CONCLUSIONS: Salvage radiotherapy for recurrent ovarian cancer resulted in local control with improved chemotherapy-free survival in carefully selected patients. Our results suggest that the consideration of pre-radiotherapy platinum resistance and pre-radiotherapy CA-125 doubling time could help with patient selection.

Major determinants of survival in recurrent endometrial cancer-the role of secondary cytoreductive surgery: a multicenter study.

OBJECTIVE: The main objective of the study was to assess the influence of different clinical and therapeutic variables on the oncological outcomes of patients with endometrial cancer relapse. In particular, we evaluated the impact of cytoreductive surgery with the achievement of complete gross resection. METHODS: This is a multicenter retrospective cohort study conducted in three centers in Italy and including all patients with first relapse of endometrial cancer from January 2010 to December 2021. RESULTS: Data from 331 women with recurrent endometrial cancer were analyzed. Secondary cytoreductive surgery was performed in 56.2% of cases (186 patients). Complete gross resection was achieved in 178 patients (95.7%). Complete gross resection conferred a statistically significant survival benefit both for post-relapse survival and post-relapse free survival (3 years post-relapse survival: 75.4% vs 56.4%, p<0.001; 3 years post-relapse free survival: 32.6% vs 26.5%, p=0.027). At multivariate Cox regression analysis, age ≥75 years, Eastern Cooperative Oncology Group Performance Status ≥2, the advanced-metastatic risk group, complete gross resection, and multiple site relapses were identified as independent significant predictors for post-relapse survival; regarding post-relapse free survival, only age ≥75, the high and advanced-metastatic risk groups, and complete gross resection confirmed their statistical significance. CONCLUSIONS: Secondary cytoreductive surgery with achievement of complete gross resection was confirmed to be an independent positive predictor for survival in patients with recurrent endometrial cancer and should be considered a valid primary treatment in the therapeutic decision-making process.

Role of minimally invasive secondary cytoreduction in patients with recurrent ovarian cancer.

OBJECTIVE: Retrospective series have shown minimally invasive secondary cytoreductive surgery is a feasible approach in selected cases of recurrent ovarian cancer. However, no predictors of minimally invasive secondary cytoreductive surgery feasibility are currently available. This study aims to identify predictive factors of minimally invasive secondary cytoreductive surgery feasibility and to compare perioperative and survival outcomes in a matched series of recurrent ovarian cancer patients who underwent secondary cytoreduction via an open or minimally invasive surgical approach. METHODS: We retrospectively identified all platinum-sensitive recurrent epithelial ovarian cancer patients who underwent minimally invasive or laparotomic secondary cytoreductive surgery between January 2013 and July 2020. Each patient underwent a preoperative positron emission tomography (PET) computerized tomography (CT) scan and diagnostic laparoscopy before secondary cytoreductive surgery. A 1:2 propensity score-matched analysis was performed to balance predictive factors of minimally invasive secondary cytoreductive surgery. RESULTS: Overall, 276 patients were identified (62 minimally invasive and 214 open), and a complete gross resection was achieved in 262 (94.9%) patients. At multivariate analysis, predictive factors for minimally invasive secondary cytoreductive surgery were neoadjuvant chemotherapy at first diagnosis (p=0.007), site of recurrence (p=0.031), and number of lesions (p=0.001). In the 1:2 propensity-matched population (39 minimally invasive and 78 open), complete gross resection was similar for both groups (p=0.082). Early post-operative complications were significantly higher in the laparotomy (33.3%) than in the minimally invasive surgery (10.3%) group (p=0.004). Only one (2.6%) patient experienced a grade >3 early post-operative complication in the minimally invasive surgery group compared with 13 (16.7%) patients in the open cohort (p<0.001). The median follow-up period was 32 months (range: 1-92) in the propensity-matched population. The median post-recurrence survival was 81 months in the minimally invasive surgery group and was not reached in the open group (p=0.11). CONCLUSIONS: Patients with single or oligometastatic recurrences can be offered minimally invasive secondary cytoreductive surgery, mainly if localized in the lymph-nodes, and/or if they received neoadjuvant chemotherapy at primary diagnosis. Minimally invasive secondary cytoreductive surgery is associated with favorable perioperative outcomes with no differences in terms of post-recurrence survival with respect to open approach.

Minimally invasive versus open pelvic exenteration in gynecological malignancies: a propensity-matched survival analysis.

OBJECTIVE: The primary endpoint of this study was to compare the disease-free survival of patients undergoing open versus minimally invasive pelvic exenteration. The secondary endpoints were cancer-specific survival and peri-operative morbidity. METHODS: A multi-center, retrospective, observational cohort study was undertaken. Patients undergoing curative and palliative anterior or total pelvic exenteration for gynecological cancer by a minimally invasive approach and an open approach between June 2010 and May 2021 were included. Patients with distant metastases were excluded. A 1:2 propensity match analysis between patients undergoing minimally invasive and open pelvic exenteration was performed to equalized baseline characteristics. RESULTS: After propensity match analysis a total of 117 patients were included, 78 (66.7%) and 39 (33.3%) in the open and minimally invasive group, respectively. No significant difference in intra-operative (23.4% vs 10.3%, p=0.13) and major post-operative complications (24.4% vs 17.9%, p=0.49) was evident between the open and minimally invasive approach. Patients undergoing open pelvic exenteration received higher rates of intra-operative transfusions (41.0% vs 17.9%, p=0.013). Median disease-free survival was 17.0 months for both the open and minimally invasive groups (p=0.63). Median cancer-specific survival was 30.0 months and 26.0 months in the open and minimally invasive groups, respectively (p=0.80). Positivity of surgical margins at final histology was the only significant factor influencing the risk of recurrence (hazard ratio (HR) 2.38, 95% CI 1.31 to 4.31) (p=0.004), while tumor diameter ≥50 mm at the time of pelvic exenteration was the only significant factor influencing the risk of death (HR 1.83, 95% CI 1.08 to 3.11) (p=0.025). CONCLUSION: In this retrospective study no survival difference was evident when minimally invasive pelvic exenteration was compared with open pelvic exenteration in patients with gynecological cancer. There was no difference in peri-operative complications, but a higher intra-operative transfusion rate was seen in the open group.

Impact of pattern of recurrence on post-relapse survival according to surgical timing in patients with advanced ovarian cancer.

OBJECTIVE: Our study aimed to evaluate the association between timing of cytoreductive surgery and pattern of presentation of the first recurrence in patients with advanced ovarian cancer. We also aimed to assess the impact of the pattern of recurrence on post-relapse overall survival according to surgical timing. METHODS: This retrospective multicenter study evaluated patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IV ovarian cancer. Patients had undergone either primary debulking surgery, early interval debulking surgery after 3-4 cycles of neoadjuvant chemotherapy, or delayed debulking surgery after 6 cycles, with minimal or no residual disease, between January 2008 and December 2015. Survival analyses were conducted using the Log-rank test and the Cox model. Cumulative incidences of the different patterns of recurrence were estimated using a competing risks methodology. RESULTS: A total of 549 patients were included: 175 (31.9%) patients had primary, 224 (40.8%) early interval, and 150 (27.3%) delayed debulking surgery. The cumulative incidence of peritoneal recurrences at 2 years was higher with increasing neoadjuvant cycles (24.4%, 30.9% and 39.2%; p=0.019). For pleural or pulmonary recurrences, it was higher after early interval surgery (9.9%, 13.0% and 4.1%; p=0.022). Median post-relapse overall survival was 33.5 months (95% confidence interval (CI) (24.3 to 44.2)), 26.8 months (95% CI (22.8 to 32.6)), and 24.5 months (95% CI (18.6 to 29.4)) for primary, early interval, and delayed debulking surgery groups, respectively (p=0.025). The pattern of recurrence in a lymph node (hazard ratio (HR) 0.42, 95% CI (0.27 to 0.64)), delayed surgery (HR 1.53, 95% CI (1.11 to 2.13)) and time to first recurrence (HR 0.95, 95% CI (0.93 to 0.96)) were associated with post-relapse overall survival. For primary and early interval surgery, lymph node recurrences were associated with significantly longer post-relapse overall survival. CONCLUSIONS: The pattern of first recurrence was associated with timing of surgery, with peritoneal recurrences being more frequent with the increasing number of cycles of neoadjuvant chemotherapy. Lymph node recurrences were associated with better prognosis, having higher post-relapse overall survival. This improved prognosis of lymphatic recurrences was not observed in patients who underwent delayed surgery.

Trabectedin plus pegylated liposomal doxorubicin in patients with disease progression after PARP inhibitor maintenance: a real-life case-control study.

OBJECTIVE: Poly (ADP-ribose) polymerase (PARP) inhibitor resistance is problematic in epithelial ovarian cancer management and sequencing strategies may be performed to overcome this issue. In this context, our study evaluated the role of non-platinum doublet pegylated liposomal doxorubicin/trabectedin in ovarian cancer platinum-sensitive patients who experienced disease progression under PARP inhibitor maintenance. METHODS: This case-control study includes patients with recurrent epithelial ovarian cancer treated between March 2016 and April 2021 who progressed under PARP inhibitor maintenance. Data of patients treated with pegylated liposomal doxorubicin/trabectedin (experimental group) were matched 1:1 with a series of patients who received platinum-based treatment (control group). The study outcomes were overall clinical benefit (including complete, partial, and stable response), progression-free survival, and overall survival. The safety of both treatments was also evaluated. RESULTS: A total of 26 patients in both groups were analyzed. Clinical benefit was achieved in 15 (57%) patients in the study group and 17 (65%) patients in the control group (p=0.38). Patients receiving pegylated liposomal doxorubicin/trabectedin had 5 months of progression-free survival, compared with 5 months in patients treated with platinum-based treatment (p=0.62). Patients in the experimental group achieved a median overall survival of 16 months compared with 19 months in the control group (p=0.26) There was no difference concerning severe toxicities (G3-G4) between groups, except for hepatic toxicity, which was experienced in 30% of the patients receiving pegylated liposomal doxorubicin/trabectedin and none in the control group (p<0.009). CONCLUSIONS: Pegylated liposomal doxorubicin/trabectedin might be an alternative option to platinum-based treatment in patients experiencing disease progression during PARP inhibitor maintenance with an acceptable toxicity profile. This might be a therapeutic option in this setting, sparing platinum compounds for subsequent relapse.

Electrochemotherapy with intravenous bleomycin for heavily pre-treated vulvar cancer patients.

OBJECTIVE: The management of vulvar cancer recurrences is complicated by patients' advanced age and comorbidities. Bleomycin-based electrochemotherapy is a potential treatment option in this setting. However, no data on long-term outcomes are available. Therefore, a multicenter observational study was designed to evaluate the 5-year results in these patients. METHODS: Data about patients and tumor characteristics, electrochemotherapy cycles, clinical response, and follow-up were recorded. Treatment procedures were performed according to the European Standard Operating Procedures of Electrochemotherapy (ESOPE) guidelines. Response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. RESULTS: Fifty-one patients (mean age 82.31±7.28 years) with squamous cell vulvar cancer underwent electrochemotherapy (median number of sessions 1; range 1-4). 20 patients had complete response and 32% of these were disease-free after 2 years (median progression-free survival 16.8 months). In 13 patients with partial response the median progression-free survival was 15.36 months, while patients with stable or progressive disease showed tumor relapse after 6.95 and 3.26 months, respectively (p<0.001). Median overall survival was 18.77, 13.07, 6.73, and 11.13 months in patients with complete response, partial response, stable disease, and progressive disease, respectively (p=0.001). CONCLUSION: Long-term follow-up of vulvar cancer patients showed reasonable tumor control after electrochemotherapy and improved progression-free survival and overall survival in responder subjects compared with non-responders. Further studies aimed at improving local response after electrochemotherapy are warranted. Thus, this approach represents a potential alternative for these patients.

Efficacy of chemotherapy according to BRCA status in patients with high-grade serous ovarian carcinoma at first platinum-sensitive relapse.

OBJECTIVE: Chemotherapy for high-grade serous ovarian cancers in platinum-sensitive relapse includes carboplatin/paclitaxel, carboplatin/gemcitabine, and carboplatin/pegylated liposomal doxorubicin. According to in vitro data, BRCA mutated patients are sensitive to replicative stress agents but BRCA status is not yet used for the choice of chemotherapy at relapse. Our aim was to assess these doublets according to BRCA status in first platinum-sensitive relapse. METHODS: The ESME ovarian cancer database comprises a multicenter retrospective cohort of patients with ovarian cancer treated in French cancer centers between January 2011 and December 2017. Patients with high-grade serous ovarian cancers at first platinum-sensitive relapse who received one of these doublets were included. The objective was to compare progression-free survival of each chemotherapy doublet according to BRCA status. RESULTS: Among the 10 263 patients in the database, 1539 patients had a first platinum-sensitive relapse: 825 BRCA wild type patients (53.6%) and 304 BRCA mutated patients (19.8%) (7 patients had a homologous recombination mutation and BRCA status was unkown for 403 patients). Median progression-free survival was longer in BRCA mutated patients than in BRCA wild type patients when receiving carboplatin/pegylated liposomal doxorubicin without maintenance treatment (15.8 vs 11.8 months; p<0.001). In contrast, we observed no difference in patients treated with carboplatin/paclitaxel (14.6 vs 14.3 months, respectively; p=0.70) or in those treated with carboplatin/gemcitabine (12.0 vs 9.8 months, respectively; p=0.18). In BRCA wild type patients without maintenance, better progression-free survival occurred with carboplatin/paclitaxel (median progression-free survival 14.3 months) than with carboplatin/gemcitabine and carboplatin/pegylated liposomal doxorubicin (9.8 and 11.8 months, respectively; p=0.017). In BRCA mutated patients without maintenance, there was no difference between the three doublets (median progression-free survival of 14.6, 12.0, and 15.8 months with carboplatin/paclitaxel, carboplatin/gemcitabine, and carboplatin/pegylated liposomal doxorubicin, respectively; p=0.40). CONCLUSION: While treatment with carboplatin/paclitaxel, carboplatin/gemcitabine, and carboplatin/pegylated liposomal doxorubicin shows comparable efficacy in BRCA mutated patients, treatment with carboplatin/paclitaxel appears to be more effective than carboplatin/gemcitabine and carboplatin/pegylated liposomal doxorubicin in BRCA wild type patients with high-grade serous ovarian cancers at first platinum-sensitive relapse.

Endometrial adenocarcinoma recurring in the lung: impact of molecular profile and role of local therapies on prognosis.

OBJECTIVES: The objective of our study was to describe the characteristics of patients with endometrial cancer diagnosed with a first recurrence involving the lung, and to describe the prognostic role of the molecular profile. We also aimed to describe the prognostic outcomes after local treatment of recurrence (resection of lung metastases or stereotactic body radiation therapy) in a group of patients with isolated lung recurrence. METHODS: This was a retrospective, single-center study between June 1995 and July 2021. The study included patients diagnosed with a first recurrence of endometrial cancer involving the lung. We defined two groups of patients: patients with isolated lung recurrence (confined to the lung) and patients with multisystemic recurrence (in the lung and other locations). RESULTS: Among 1413 patients diagnosed with endometrial cancer in stage IA to IVA of the International Federation of Gynecology and Obstetrics (FIGO) 2009, 64 (4.5%) patients had a first recurrence involving the lung. Of these, 15 (39.1%) were of a non-specific molecular profile, 16 (25%) were p53-abnormal, 15 (23.4%) were mismatch-repair deficient, and 0% POLE-mutated. P53-abnormal patients had the shortest 3 year progression-free survival after recurrence and those with mismatch-repair deficient had the longest 3 year progression-free survival (14.3% (range; 1.6-40.3) and 47.6% (range; 9.1-79.5) respectively, p=0.001). We found no differences on overall survival after recurrence by molecular profile. Thirty-one of 64 (48.4%) patients had an isolated recurrence in the lung, and 16 (25%) patients received local treatment. When comparing patients with isolated lung recurrence, locally treated patients had a longer median progression-free survival than patients treated systemically (41.9 (range, 15.4-NA) vs 7.8 (range, 7.2-10.6) months respectively, p=0.029), a complete response rate of 80% for stereotactic body radiation therapy and a complete resection of 90.9% for surgery. CONCLUSION: Although few patients will benefit from local treatment (stereotactic body radiation therapy or resection) after a recurrence involving the lung, local therapies might be considered as an option in oligometastatic lung recurrences as they achieve high local control rates and better oncological outcomes than systemic treatment alone.

Machine learning endometrial cancer risk prediction model: integrating guidelines of European Society for Medical Oncology with the tumor immune framework.

OBJECTIVE: Current prognostic factors for endometrial cancer are not sufficient to predict recurrence in early stages. Treatment choices are based on the prognostic factors included in the risk classes defined by the ESMO-ESGO-ESTRO (European Society for Medical Oncology-European Society of Gynaecological Oncology-European Society for Radiotherapy and Oncology) consensus conference with the new biomolecular classification based on POLE, TP53, and microsatellite instability status. However, a minority of early stage cases relapse regardless of their low risk profiles. Integration of the immune context status to existing molecular based models has not been fully evaluated. This study aims to investigate whether the integration of the immune landscape in the tumor microenvironment could improve clinical risk prediction models and allow better profiling of early stages. METHODS: Leveraging the potential of in silico deconvolution tools, we estimated the relative abundances of immune populations in public data and then applied feature selection methods to generate a machine learning based model for disease free survival probability prediction. RESULTS: We included information on International Federation of Gynecology and Obstetrics (FIGO) stage, tumor mutational burden, microsatellite instability, POLEmut status, interferon γ signature, and relative abundances of monocytes, natural killer cells, and CD4+T cells to build a relapse prediction model and obtained a balanced accuracy of 69%. We further identified two novel early stage profiles that undergo different pathways of recurrence. CONCLUSION: This study presents an extension of current prognostic factors for endometrial cancer by exploiting machine learning models and deconvolution techniques on available public biomolecular data. Prospective clinical trials are advisable to validate the early stage stratification.

Prognostic factors in patients with endometrial cancer with isolated lymphatic recurrence.

OBJECTIVE: To analyze the clinicopathological features and outcomes in patients with endometrial cancer with isolated lymphatic recurrence after lymphadenectomy, stratified by different isolated lymphatic recurrence sites and treatment approaches. METHODS: We retrospectively reviewed all surgically treated patients with endometrial cancer, identifying those with recurrence. We defined primary isolated lymphatic recurrence as the first and unique evidence of recurrence in lymph node-bearing areas, without concomitant vaginal, hematogenous, or peritoneal recurrence. Isolated lymphatic recurrences were classified as pelvic, para-aortic, distant, or multiple sites. Our primary outcome was cause-specific survival after diagnosis of the recurrence. RESULTS: Among 4216 patients with surgically staged endometrial cancer, we identified 66 (1.6%) women with isolated lymphatic recurrence. The overall median cause-specific survival for patients with isolated lymphatic recurrence was 24 months. Although cause-specific survival was not significantly different between the four isolated lymphatic recurrence groups (p=0.21), 7 of 15 (47%) patients with isolated lymphatic recurrence in the para-aortic area were long-term survivors. At multivariate Cox regression, the absence of lymphovascular space invasion and grade 1 histology in the primary tumor were significantly associated with improved cause-specific survival. In addition, patients with isolated lymphatic recurrence who underwent surgery for recurrence (with/without other associated therapies) had improved cause-specific survival compared with patients who did not undergo surgery, also after adjusting for age. CONCLUSIONS: Low-grade histology and absence of lymphovascular space invasion in the primary tumor were predictors of improved prognosis in patients with endometrial cancer with isolated lymphatic recurrence. In addition, in this retrospective cohort, patients with isolated lymphatic recurrence who were selected for eradicative surgical treatment had improved cause-specific survival.