Development of a Prognostic Model for Early Breast Cancer Integrating Neutrophil to Lymphocyte Ratio and Clinical-Pathological Characteristics.

BACKGROUND: Breast cancer-related inflammation is critical in tumorigenesis, cancer progression, and patient prognosis. Several inflammatory markers derived from peripheral blood cells count, such as the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII) are considered as prognostic markers in several types of malignancy. METHODS: We investigate and validate a prognostic model in early patients with breast cancer to predict disease-free survival (DFS) based on readily available baseline clinicopathological prognostic factors and preoperative peripheral blood-derived indexes. RESULTS: We analyzed a training cohort of 710 patients and 2 external validation cohorts of 980 and 157 patients with breast cancer, respectively, with different demographic origins. An elevated preoperative NLR is a better DFS predictor than others scores. The prognostic model generated in this study was able to classify patients into 3 groups with different risks of relapse based on ECOG-PS, presence of comorbidities, T and N stage, PgR status, and NLR. CONCLUSION: Prognostic models derived from the combination of clinicopathological features and peripheral blood indices, such as NLR, represent attractive markers mainly because they are easily detectable and applicable in daily clinical practice. More comprehensive prospective studies are needed to unveil their actual effectiveness.

Expanding the Use of HIPEC in Ovarian Cancer at Time of Interval Debulking Surgery to FIGO Stage IV and After 6 Cycles of Neoadjuvant Chemotherapy: A Prospective Analysis on Perioperative and Oncologic Outcomes.

BACKGROUND: Randomized data on patients with FIGO stage III ovarian cancer receiving ≤ 3 cycles of neoadjuvant chemotherapy (NACT) showed that hyperthermic intraperitoneal chemotherapy (HIPEC) after interval debulking surgery (IDS) improved patient's survival. We assessed the perioperative outcomes and PFS of FIGO stage IV and/or patients receiving up to 6 cycles of NACT undergoing IDS+HIPEC. METHODS: Prospectively collected cases from January 1, 2019 to July 31, 2022 were included. Patients underwent HIPEC if: age ≥ 18 years but < 75 years, body mass index ≤ 35 kg/m2, ASA score ≤ 2, FIGO stage III/IV epithelial disease treated with up to 6 cycles of NACT, and residual disease < 2.5 mm. RESULTS: A total of 205 patients were included. No difference was found in baseline characteristics between FIGO Stage III and IV patients, whereas rate of stable disease after NACT (p = 0.004), mean surgical complexity score at IDS (p = 0.001), and bowel resection rate (p = 0.046) were higher in patients undergoing delayed IDS. A lower rate of patients with at least one G3-G5 postoperative complications was observed in FIGO stage IV versus FIGO stage III disease (5.3% vs. 14.0%; p = 0.052). This difference was confirmed at multivariable analysis (odds ratio [OR] 0.24; 95% confidence interval [CI] 0.07-0.80; p = 0.02), whereas age, SCS, bowel resection, and number of cycles did not affect postoperative complications. No difference in PFS was identified neither between FIGO stage III and IV patients (p = 0.44), nor between 3 and 4 versus > 4 cycles of NACT (p = 0.85). CONCLUSIONS: Because of the absence of additional complications and positive survival outcomes, HIPEC administration can be considered in selected FIGO stage IV and patients receiving > 4 cycles of NACT.

Distribution and prognostic role of BRCA status in elderly ovarian cancer patients.

OBJECTIVE: In the era of target therapy and personalized medicine, BRCA mutational status has a major influence on survival in ovarian cancer patients. Our aim is to verify if the poorer prognosis of elderly ovarian cancer patients can be related to the biology of the tumor beyond their own morbidities and/or suboptimal treatments. METHODS: This is a retrospective single-institution study evaluating prognosis of patients with a diagnosis of ovarian cancer and known BRCA status. We collected clinical and surgical characteristics and the distribution of BRCA mutational status according to age groups. RESULTS: 1840 patients were included in the analysis. The rate of BRCA mutated decreased over age-range from 49.7% in patients aged <50 years to 18.8% in ≥80 years old women. The prognostic role of BRCA status on survival is maintained when focusing on the elderly population, with improved Disease Free Survival (27.2 months vs 16.5 months for BRCA mutated and wild type respectively, p = 0.001) and Cancer Specific Survival (117.6 months vs 43.1 months for BRCA mutated and wild type respectively, p = 0.001) for BRCAmut compared to BRCAwt patients. In the multivariable analysis, among elderly women, upfront surgery and BRCA mutation are independent factors affecting survival. CONCLUSIONS: Elderly patients experiment a poorer prognosis due to multiple factors that include both their medical condition and comorbidities, under-treatment and most importantly disease characteristics. We found that beyond disparities, BRCA mutation is still the strongest independent prognostic factor affecting both the risk of recurrence and death due to disease.

Clinical characteristics and survival outcome of early-stage, high-grade, serous tubo-ovarian carcinoma according to BRCA mutational status.

OBJECTIVE: To investigate the role of BRCA1/2 mutations in early ovarian cancer (eOC) (International Federation of Gynecology and Obstetrics FIGO 2014 stage I-II), and its impact on prognosis after relapse. METHODS: In this multicenter retrospective study, clinical and survival data from high-grade serous (HGS)-eOC patients at presentation and recurrence were compared according to BRCA status: BRCA-mutated (BRCAmut) vs. BRCA wild-type (BRCAwt). RESULTS: Among 191 HGS-eOC patients, 89 were BRCAmut and 102 BRCAwt. There was no significant difference according to the BRCA status in terms of Progression-Free Survival (PFS). A longer Overall Survival (OS) was found in BRCAmut patients. Stage I patients had significantly improved PFS vs stage II, regardless of BRCA status. At multivariate analysis, stage at diagnosis was the only variable with a significant effect on PFS. No factors were significantly relevant on OS, albeit younger age and BRCA mutation showed a slight impact. Post-Recurrence Survival (PRS) in the BRCAmut population was significantly improved compared with BRCAwt. At multivariate analysis, Secondary Cytoreductive Surgery was the strongest predictor for longer PRS, followed by PARPi maintenance at recurrence. CONCLUSIONS: BRCA-status is not a prognostic factor in early ovarian cancer regarding PFS. However, our data suggest a better prognosis after relapse in BRCAm population.

Feasibility and operative outcomes of surgery in the liver area in advanced ovarian cancer.

OBJECTIVE: The study aimed to characterize intra-and postoperative complications according to a standardized anatomo-surgical classification for ovarian cancer metastases in the liver area. METHODS: Data from all patients with advanced ovarian cancer undergoing primary or secondary surgery with perihepatic liver involvement (May-2016 to May-2022), were retrospectively retrieved and classified according to a standardized anatomo-surgical classification, and clustered into four Classes: Class I "Peritoneal", Class II "Hepatoceliac-lymph-nodes", Class III "Parenchymal" and Class IV Mixed (≥ 2 classes). RESULTS: Data from 615 patients were collected. Intraoperative complications were observed in 15%, and severe postoperative complications in 17.6% of cases. While surgical complexity scores were similar, Class IV had longer operative times, higher blood loss, and a 30.4% intraoperative transfusion rate. Class II showed a higher prevalence of vascular injuries (8%). Classes II and IV were significantly associated with severe postoperative complications. Specific complications varied among classes, such as perihepatic collection and intrahepatic hematoma/abscess in Class III (p = 0.003, p < 0.001, respectively), and pleuric effusion, sepsis, anemia, and "other complications" in Class IV (p = 0.002, p = 0.004, p = 0.03, p = 0.03, respectively). Multivariable analysis identified Class II and IV (Class II: OR 4.991, p = 0.045; Class IV: OR 5.331, p = 0.030), Surgical Complexity Score group 3 (OR:3.922, p = 0.003), and the presence of residual tumor (OR:1.748, p = 0.048) as independent risk factors for severe postoperative complications. CONCLUSIONS: Liver procedures during advanced ovarian cancer surgery are feasible with acceptable complication rates According to the anatomo-surgical classification, metastatic patterns are related to both different surgical outcomes and postoperative complication profiles.

Real world data of niraparib in platinum sensitive relapsed ovarian cancer: A multicenter experience of the MITO group.

OBJECTIVE: PARP (poly adenosine diphosphate [ADP]-ribose polymerase) inhibitors are approved as maintenance therapy in platinum sensitive ovarian cancer (OC), in first line and in the recurrent setting, regardless of BRCA mutational status. Real-world data after the introduction of these agents are needed to evaluate whether the benefit observed in phase III randomized clinical trials can be translated into clinical practice. The aim of our study was to provide real-life data on efficacy and safety of niraparib administered as maintenance in platinum sensitive relapsed OC patients (PSROC). METHODS: This retrospective/prospective observational study included relapsed OC patients that received niraparib as maintenance, at the time of platinum sensitive recurrence within the Italian expanded-access program. Clinical data at the time of diagnosis and at the time of recurrence were collected and analyzed. Median progression free survival (PFS) and overall survival (OS) were calculated as the time from start of niraparib treatment to subsequent radiologically confirmed relapse and death or last contact, respectively. RESULTS: Among 304 eligible patients, 260 (85%) had BRCA wild-type tumor and 36. (11.9%) were BRCA mutated. Median PFS was 9.1 months (95% CI: 6.9-11.2) and 10.3 months (95% CI: 7.0-13.5) in the BRCAwt and BRCAmut cohorts, respectively. Furthermore, median OS was 41.7 months (95% CI: 31.6-41.9) and 34.6 months (95% CI: N.E.) in the BRCAwt and BRCAmut cohorts, respectively. CONCLUSION: Data from this large real-life dataset suggested that maintenance with niraparib in the real-life setting of platinum sensitive OC recurrence is effective and well tolerated.

Impact of targeted agents on survival of chronic lymphocytic leukemia patients age >65 relative to age- and sex-matched population.

Pooled analysis of six mature phase 3 trials (RESONATE2, ILLUMINATE, ALLIANCE041202, ELEVATE-TN, CLL14, and GLOW) evaluating Bruton's tyrosine kinase inhibitors (BTKis) and venetoclax-based treatments suggests that these agents have reduced but not completely eliminated the overall survival (OS) gap between elderly chronic lymphocytic leukemia (CLL) patients and the age and sex-matched general population (AGMGP).

Robotic-assisted versus conventional laparoscopic surgery in the management of obese patients with early endometrial cancer in the sentinel lymph node era: a randomized controlled study (RObese).

BACKGROUND: Nearly 65% of patients with endometrial cancer who undergo primary hysterectomy have concurrent obesity. Retrospective data show advantages in using robotic surgery in these patients compared with conventional laparoscopy, namely lower conversion rate, increased rate of same-day discharge, and reduced blood loss. Nevertheless, to date no prospective randomized controlled trials have compared laparoscopic surgery versus robotic-assisted surgery in morbidly obese patients. PRIMARY OBJECTIVE: The robotic-assisted versus conventional laparoscopic surgery in the management of obese patients with early endometrial cancer in the sentinel lymph node era: a randomized controlled study (RObese) trial aims to find the most appropriate minimally invasive surgical approach in morbidly obese patients with endometrial carcinoma. STUDY HYPOTHESIS: Robotic surgery will reduce conversions to laparotomy in endometrial cancer patients with obesity compared with those who undergo surgery with conventional laparoscopy. TRIAL DESIGN: This phase III multi-institutional study will randomize consecutive obese women with apparent early-stage endometrial cancer to either laparoscopic or robot-assisted surgery. MAJOR INCLUSION/EXCLUSION RITERIA: The RObese trial will include obese (BMI≥30 kg/m2) patients aged over 18 years with apparent 2009 Federation of Gynecology and Obstetrics (FIGO) stage IA-IB endometriod endometrial cancer. PRIMARY ENDPOINT: Conversion rate to laparotomy between laparoscopic surgery versus robot-assisted surgery. SAMPLE SIZE: RObese is a superiority trial. The clinical superiority margin for this study is defined as a difference in conversion rate of -6%. Assuming a significance level of 0.05 and a power of 80%, the study plans to randomize 566 patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Patient recruitment will be completed by 2026, and follow-up will be completed by 2029 with presentation of data shortly thereafter. Two interim analyses are planned: one after the first 188 and the second after 376 randomized patients. TRIAL REGISTRATION: NCT05974995.

Concurrent endometrial cancer in atypical endometrial hyperplasia and the role of sentinel lymph nodes: clinical insights from a multicenter experience.

OBJECTIVE: This study aimed to evaluate the prevalence of concurrent endometrial cancer in patients pre-operatively diagnosed with atypical endometrial hyperplasia undergoing hysterectomy. Additionally, we assessed the occurrence of high to intermediate-risk and high-risk tumors according to the ESGO-ESTRO-ESP classification. The study also compared surgical outcomes and complications between patients undergoing simple hysterectomy and those undergoing hysterectomy with sentinel lymph node biopsy. METHODS: In this multicenter retrospective study, patients with a pre-operative diagnosis of atypical endometrial hyperplasia were identified and divided into two groups: Group 1, which included patients treated with total hysterectomy with or without bilateral salpingo-oophorectomy, and Group 2, where sentinel lymph node biopsy was incorporated into the standard surgical treatment. RESULTS: Among 460 patients with atypical endometrial hyperplasia, 192 received standard surgical management (Group 1) and 268 underwent sentinel lymph node biopsy (Group 2). A total of 47.2% (95% CI 42.6% to 51.7%) of patients were upgraded to endometrial cancer on final histopathological examination. High to intermediate-risk and high-risk tumors constituted 12.3% and 9.2% in Group 2 and 7.4% and 3.7% in Group 1. Lymph node metastases were identified in 7.6% of patients with concurrent endometrial cancer who underwent nodal assessment with at least unilateral mapping. Of the 12 sentinel lymph node metastases, 75.0% were micrometastases, 16.7% macrometastases, and 8.3% isolated tumor cells. No significant differences were found in estimated blood loss, operative time, and intra-operative and post-operative complications between the two groups. The rate of patients undergoing sentinel lymph node biopsy doubled every 2 years (OR 2.010, p<0.001), reaching 79.1% in the last 2 years. CONCLUSION: This study found a prevalence of concurrent endometrial cancer of 47.2%, and sentinel lymph node biopsy provided prognostic and therapeutic information in 60.8% of cases. It also allowed for the adjustment of adjuvant therapy in 12.3% of high to intermediate-risk patients without increasing operative time or complication rates.

Epithelial ovarian cancer and brain metastases: might the BRCA status, PARP inhibitor administration, and surgical treatment impact the survival?

OBJECTIVE: To evaluate disease characteristics and survival according to BRCA status, administration of poly-(ADP-ribose) polymerase inhibitors (PARPi), and surgery in patients with ovarian cancer and brain metastases. METHODS: This is a monocentric retrospective cohort of patients with ovarian cancer and brain metastases treated between 2000 and 2021. Data were collected by a retrospective review of medical records and analyzed according to: (1) BRCA mutation; (2) PARPi before and after brain metastases; (3) surgery for brain metastases. RESULTS: Eighty-five patients with ovarian cancer and brain metastasis and known BRCA status (31 BRCA mutated (BRCAm), 54 BRCA wild-type (BRCAwt)) were analyzed. Twenty-two patients had received PARPi before brain metastases diagnosis (11 BRCAm, 11 BRCAwt) and 12 after (8 BRCAm, 4 BRCAwt). Brain metastases occurred >1 year later in patients who had received previous PARPi. Survival was longer in the BRCAm group (median post-brain metastasis survival: BRCAm 23 months vs BRCAwt 8 months, p=0.0015). No differences were found based on BRCA status analyzing the population who did not receive PARPi after brain metastasis (median post-brain metastasis survival: BRCAm 8 months vs BRCAwt 8 months, p=0.31). In the BRCAm group, survival was worse in patients who had received previous PARPi (median post-brain metastasis survival: PARPi before, 7 months vs no-PARPi before, 24 months, p=0.003). If PARPi was administered after brain metastases, survival of the overall population improved (median post-brain metastasis survival: PARPi after, 46 months vs no-PARPi after, 8 months, p=0.00038).In cases of surgery for brain metastases, the prognosis seemed better (median post-brain metastasis survival: surgery 13 months vs no-surgery 8 months, p=0.036). Three variables were significantly associated with prolonged survival at multivariate analysis: BRCA mutation, multimodal treatment, and ≤1 previous chemotherapy line. CONCLUSIONS: BRCA mutations might impact brain metastasis occurrence and lead to better outcomes. In a multimodal treatment, surgery seems to affect survival even in cases of extracranial disease. PARPi use should be considered as it seems to prolong survival if administered after brain metastasis.

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.

Arthroscopic management of isolated partial-thickness rotator cuff tears.

PURPOSE: The aim of the present study is to provide a comprehensive review on the surgical outcomes following arthroscopic treatments of partial-thickness rotator cuff tears (PT-RCTs) and to compare the postoperative American Shoulder and Elbow Surgeons (ASES) score following in situ transtendon repair and tear completion, followed by repair. METHODS: Medline, EMBASE, Scopus, CINAHL and CENTRAL bibliographic databases were searched. Papers including patients with PT-RCTs of any grade who underwent treatment using debridement, in situ transtendon repair, tear completion and repair or bioinductive collagen implants were reviewed. Primary PT-RCTs were the sole indication for surgery. Primary postoperative outcomes assessed included the ASES score, the Absolute Constant-Murley score, the Simple Shoulder Test, the Visual Analogue Scale, the University of California-Los Angeles Shoulder Scale, the Western Ontario Rotator Cuff Score, range of motion, complications and revisions. A meta-analysis of comparative studies compared the postoperative ASES score between patients treated with in situ transtendon repair versus tear completion repair. RESULTS: Twenty-eight studies were included. The ASES score was reported by four comparative studies with contrasting results. The heterogeneity was high (I2 = 86%), and effect sizes ranged from -0.49 in favour of the tear completion and repair technique to an effect size of +1.07 favouring in situ transtendon repair. The overall effect size of 0.02 suggests an equivalence between the two techniques in terms of the ASES score. Two studies with a total sample size of 111 patients reported on debridement, and four studies with a total sample size of 155 patients reported on bioinductive collagen implants. CONCLUSION: Debridement alone is suitable for Ellman grades I-II PT-RCTs. In situ transtendon and tear completion repair techniques yield similar postoperative outcomes. Bioinductive collagen implants hold promise but lack long-term efficacy data. High-quality comparative studies are needed to determine the best treatment for PT-RCTs. LEVEL OF EVIDENCE: Level IV.

Humoral and T-Cell Immune Response After 3 Doses of Messenger RNA Severe Acute Respiratory Syndrome Coronavirus 2 Vaccines in Fragile Patients: The Italian VAX4FRAIL Study.

BACKGROUND: Patients with solid or hematological tumors or neurological and immune-inflammatory disorders are potentially fragile subjects at increased risk of experiencing severe coronavirus disease 2019 and an inadequate response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. METHODS: We designed a prospective Italian multicenter study to assess humoral and T-cell responses to SARS-CoV-2 vaccination in patients (n = 378) with solid tumors (ST), hematological malignancies (HM), neurological disorders (ND), and immunorheumatological diseases (ID). A group of healthy controls was also included. We analyzed the immunogenicity of the primary vaccination schedule and booster dose. RESULTS: The overall seroconversion rate in patients after 2 doses was 62.1%. Significantly lower rates were observed in HM (52.4%) and ID (51.9%) than in ST (95.6%) and ND (70.7%); a lower median antibody level was detected in HM and ID versus ST and ND (P < .0001). Similar rates of patients with a positive SARS-CoV-2 T-cell response were found in all disease groups, with a higher level observed in ND. The booster dose improved the humoral response in all disease groups, although to a lesser extent in HM patients, whereas the T-cell response increased similarly in all groups. In the multivariable logistic model, independent predictors of seroconversion were disease subgroup, treatment type, and age. Ongoing treatment known to affect the immune system was associated with the worst humoral response to vaccination (P < .0001) but had no effect on T-cell responses. CONCLUSIONS: Immunosuppressive treatment more than disease type per se is a risk factor for a low humoral response after vaccination. The booster dose can improve both humoral and T-cell responses.

Incorporating weekly carboplatin in anthracycline and paclitaxel-containing neoadjuvant chemotherapy for triple-negative breast cancer: propensity-score matching analysis and TIL evaluation.

BACKGROUND: The generation of data capturing the risk-benefit ratio of incorporating carboplatin (Cb) to neoadjuvant chemotherapy (NACT) for triple-negative breast cancer (TNBC) in a clinical practice setting is urgently needed. Tumour-infiltrating lymphocytes (TILs) have an established role in TNBC receiving NACT, however, the role of TIL dynamics under NACT exposure in patients receiving the current standard of care is largely uncharted. METHODS: Consecutive TNBC patients receiving anthracycline-taxane [A-T] +/- Cb NACT at three Institutions were enrolled. Stromal-TILs were evaluated on pre-NACT and residual disease (RD) specimens. In the clinical cohort, propensity-score-matching was used to control selection bias. RESULTS: In total, 247 patients were included (A-T = 40.5%, A-TCb = 59.5%). After propensity-score-matching, pCR was significantly higher for A-TCb vs A-T (51.9% vs 34.2%, multivariate: OR = 2.40, P = 0.01). No differences in grade ≥3 haematological toxicities were observed. TILs increased from baseline to RD in the overall population and across A-T/A-TCb subgroups. TIL increase from baseline to RD was positively and independently associated with distant disease-free survival (multivariate: HR = 0.43, P = 0.05). CONCLUSIONS: We confirmed in a clinical practice setting of TNBC patients receiving A-T NACT that the incorporation of weekly Cb significantly improved pCR. In addition, A-T +/- Cb enhanced immune infiltration from baseline to RD. Finally, we reported a positive independent prognostic role of TIL increase after NACT exposure.

Immune-related adverse events and disease outcomes after the third dose of SARS-CoV-2 mRNA-BNT162b2 vaccine in cancer patients receiving immune checkpoint inhibitors.

BACKGROUND: The clinical implications of the third dose of coronavirus disease 2019 (COVID-19) vaccines in patients receiving immune checkpoint inhibitors are currently unknown. We performed a prospective analysis of the Vax-On-Third study to investigate the effects of antibody response on immune-related adverse events (irAEs) and disease outcomes. METHODS: Recipients of the booster dose of SARS-CoV-2 mRNA-BNT162b2 vaccine who had received at least one course of an anti-PD-1/PD-L1 treatment before vaccination for an advanced solid malignancy were eligible. RESULTS: The current analysis included 56 patients with metastatic disease (median age: 66 years; male: 71%), most of whom had a lung cancer diagnosis and were being treated with pembrolizumab- or nivolumab-based regimens. The optimal cut-point antibody titer of 486 BAU/mL allowed a dichotomization of recipients into low-responders (Low-R, < 486 BAU/mL) or high-responders (High-R, ≥ 486 BAU/mL). After a median follow-up time of 226 days, 21.4% of patients experienced moderate to severe irAEs without any recrudescence of immune toxicities preceding the booster dose. The frequencies of irAE before and after the third dose did not differ, but an increase in the cumulative incidence of immuno-related thyroiditis was observed within the High-R subgroup. On multivariate analysis, an enhanced humoral response correlated with a better outcome in terms of durable clinical benefit, which resulted in a significant reduction in the risk of disease control loss but not mortality. CONCLUSIONS: Our findings would strengthen the recommendation not to change anti-PD-1/PD-L1 treatment plans based on current or future immunization schedules, implying that all these patients should be closely monitored.

Predictors of ibrutinib-associated atrial fibrillation: 5-year follow-up of a prospective study.

Ibrutinib-associated atrial fibrillation (IRAF) emerged among the adverse events of major interests in ibrutinib-treated patients as real-world studies showed a higher incidence compared to clinical trials. We prospectively analyzed predictors of IRAF in 43 single-center consecutive patients affected by chronic lymphocytic leukemia that started therapy with ibrutinib between 2015 and 2017. Key secondary endpoints were to describe the management of IRAF and survival outcomes. During a median follow-up period of 52 months, we registered 45 CV events, with a total of 23 AF events in 13 patients (CI 30.0% (95% CI: 16.5-43.9)). Pre-existent cardiovascular risk factors, in particular hypertension, a previous history of AF and a high Shanafelt risk score emerged as predictors of IRAF. Baseline echocardiographic evaluation of left atrial (LA) dimensions confirmed to predict IRAF occurrence and cut-off values were identified in our cohort: 32 mm for LA diameter and 18 cm2 for LA area. No difference in progression free survival and overall survival emerged in patients experiencing IRAF. Following AF, anticoagulation was started in all eligible patients, and cardioactive therapy was accordingly modified. Echocardiography represents a highly reproducible and widespread tool to be included in the work-up of ibrutinib candidates; the identification of IRAF predictors represents a useful guide to clinical practice.

Survival associated with extent of radical hysterectomy in early-stage cervical cancer: a subanalysis of the Surveillance in Cervical CANcer (SCCAN) collaborative study.

BACKGROUND: International guidelines recommend tailoring the radicality of hysterectomy according to the known preoperative tumor characteristics in patients with early-stage cervical cancer. OBJECTIVE: This study aimed to assess whether increased radicality had an effect on 5-year disease-free survival in patients with early-stage cervical cancer undergoing radical hysterectomy. The secondary aims were 5-year overall survival and pattern of recurrence. STUDY DESIGN: This was an international, multicenter, retrospective study from the Surveillance in Cervical CANcer (SCCAN) collaborative cohort. Patients with the International Federation of Gynecology and Obstetrics 2009 stage IB1 and IIA1 who underwent open type B/C1/C2 radical hysterectomy according to Querleu-Morrow classification between January 2007 and December 2016, who did not undergo neoadjuvant chemotherapy and who had negative lymph nodes and free surgical margins at final histology, were included. Descriptive statistics and survival analyses were performed. Patients were stratified according to pathologic tumor diameter. Propensity score match analysis was performed to balance baseline characteristics in patients undergoing nerve-sparing and non-nerve-sparing radical hysterectomy. RESULTS: A total of 1257 patients were included. Of note, 883 patients (70.2%) underwent nerve-sparing radical hysterectomy, and 374 patients (29.8%) underwent non-nerve-sparing radical hysterectomy. Baseline differences between the study groups were found for tumor stage and diameter (higher use of non-nerve-sparing radical hysterectomy for tumors >2 cm or with vaginal involvement; P<.0001). The use of adjuvant therapy in patients undergoing nerve-sparing and non-nerve-sparing radical hysterectomy was 27.3% vs 28.6%, respectively (P=.63). Five-year disease-free survival in patients undergoing nerve-sparing vs non-nerve-sparing radical hysterectomy was 90.1% (95% confidence interval, 87.9-92.2) vs 93.8% (95% confidence interval, 91.1-96.5), respectively (P=.047). Non-nerve-sparing radical hysterectomy was independently associated with better disease-free survival at multivariable analysis performed on the entire cohort (hazard ratio, 0.50; 95% confidence interval, 0.31-0.81; P=.004). Furthermore, 5-year overall survival in patients undergoing nerve-sparing vs non-nerve-sparing radical hysterectomy was 95.7% (95% confidence interval, 94.1-97.2) vs non-nerve-sparing 96.5% (95% confidence interval, 94.3-98.7), respectively (P=.78). In patients with a tumor diameter ≤20 mm, 5-year disease-free survival was 94.7% in nerve-sparing radical hysterectomy vs 96.2% in non-nerve-sparing radical hysterectomy (P=.22). In patients with tumors between 21 and 40 mm, 5-year disease-free survival was 90.3% in non-nerve-sparing radical hysterectomy vs 83.1% in nerve-sparing radical hysterectomy (P=.016) (no significant difference in the rate of adjuvant treatment in this subgroup, P=.47). This was confirmed after propensity match score analysis (balancing the 2 study groups). The pattern of recurrence in the propensity-matched population did not demonstrate any difference (P=.70). CONCLUSION: For tumors ≤20 mm, no survival difference was found with more radical hysterectomy. For tumors between 21 and 40 mm, a more radical hysterectomy was associated with improved 5-year disease-free survival. No difference in the pattern of recurrence according to the extent of radicality was observed. Non-nerve-sparing radical hysterectomy was associated with better 5-year disease-free survival than nerve-sparing radical hysterectomy after propensity score match analysis.

Quality of life in patients with advanced ovarian cancer after primary debulking surgery versus neoadjuvant chemotherapy: Results from the randomised SCORPION trial (NCT01461850).

OBJECTIVE: To investigate the effect of treatment with neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS), versus primary debulking surgery (PDS), on quality of life (QoL) in patients with advanced epithelial ovarian cancer (EOC). DESIGN: Randomised trial conducted in a single institution. SETTING: Division of Gynaecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. SAMPLE: Patients with stage-IIIC/IV EOC and high tumour load. METHODS: Patients were randomised (1:1) to undergo either PDS (PDS group) or NACT followed by IDS (NACT/IDS group). MAIN OUTCOME MEASURES: Quality-of-life (QoL) data, assessed using the European Organization for Research and Treatment of Cancer core QoL questionnaire (QLQ-C30) and ovarian cancer module (OV28); co-primary outcomes were the QLQ-C30 global health score at 12 months (cross-sectional analysis) and the difference in mean QLQ-C30 global health score over time between treatment groups (longitudinal analysis). RESULTS: From October 2011 to May 2016, 171 patients were enrolled (PDS = 84; NACT/IDS = 87). We observed no clinical or statistically significant difference between treatment groups in any of the QoL functioning scales at 12 months, including QLQ-C30 global health score (NACT/IDS group vs PDS group, mean difference 4.7, 95% CI -4.99 to 14.4, p = 0.340). Over time, we found lower global health scores for those undergoing PDS than for those receiving NACT (difference in mean score 6.27, 95% CI 0.440-12.11, p = 0.035), albeit this was not clinically relevant. CONCLUSIONS: We found no difference in global QoL related to treatment approach at 12 months, even though patients in the NACT/IDS group reported better global health scores across the 12-month period compared with the PDS group; these findings further confirm that NACT/IDS might be a feasible option for patients unsuitable for PDS.

Effect of exercise across the head and neck cancer continuum: a systematic review of randomized controlled trials.

PURPOSE: This study aims to systematically explore the impact of physical exercise as supportive therapy for head and neck cancer. METHODS: A systematic search on PubMed/MEDLINE, Cochrane, and SPORTDiscus was conducted. Randomized controlled trials exploring the effects of a physical exercise intervention in comparison with usual care on outcomes in patients with head and neck cancer were selected. The RoB 2 tool was used to determine the study quality. The extracted data are reported as qualitative synthesis. RESULTS: Among the 527 records examined, nine studies were included. No trials investigating exercise as prehabilitation were found, whereas eight studies involving 452 patients with head and neck cancer were conducted during anticancer treatment. Most trials did not report improvements in body mass index or body composition, while 2/4 and 3/5 investigations found a significant increase in muscle strength and cardiorespiratory fitness, respectively. Regarding the patients' reported outcomes, 4 out of 7 studies observed enhancements in some domains of quality of life, and two trials out of 3 detected an amelioration in fatigue following the exercise intervention. Analyzing the exercise programs, it seems that combining aerobic and resistance training could be more beneficial compared to a single type of full-body exercise in counteracting physical decline and controlling symptoms in the anticancer therapy phase. One trial has investigated the effect of resistance exercise on patients who had terminated the anticancer treatments, reporting significant improvements in lean mass, muscle strength, and quality of life. CONCLUSION: Exercise may be a promising approach in patients with head and neck cancer. Future studies are needed to consolidate these results.

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.