Are biomarkers expression and clinical-pathological factors predictive markers of the efficacy of neoadjuvant chemotherapy for locally advanced cervical cancer?

INTRODUCTION: To predict the overall pathologic response to neoadjuvant chemotherapy (NACT) of patients with locally advanced cervical cancer (LACC) creating a prediction model based on clinical-pathological factors and biomarkers (p53, Bcl1 and Bcl2) and to evaluate the prognostic outcomes of NACT. MATERIALS AND METHODS: This is a retrospective study of 88 consecutive patients with LACC who underwent NACT followed by nerve sparing surgery with retroperitoneal lymphadenectomy at National Cancer Institute of Milan, between January 2000 and June 2013. Clinical pathologic data were retrieved from the institutional database. Biomarkers (p53, Bcl1 and Bcl2) were evaluated before and after NACT in the specimen. To investigate their role as predictors of response, we tried several statistical machine learning algorithms. RESULTS: Responders to NACT showed a 5-years survival between 100%(CR) and 85.7%(PR). Clinical factors were the most important predictor of response. Age, BMI and grade represented the most important predictors of response at random forest analysis. Tree-based boosting revealed that after adjusting for other prognostic factors, age, grade, BMI and tumor size were independent predictors of response to NACT, while p53 was moderately related to response to NACT. Area under the curve (crude estimate): 0.871. Whereas Bcl1 and Bcl2, were not predictors for response to NACT. The final logistic regression reported that grade was the only significant predictor of response to NACT. CONCLUSION: Combined model that included clinical pathologic variables plus p53 cannot predict response to NACT. Despite this, NACT remain a safe treatment in chemosensitive patients avoiding collateral sequelae related to chemo-radiotherapy.

Endometriosis-associated ovarian cancer: a different clinical entity.

OBJECTIVE: To compare survival outcomes and patterns of recurrence between endometriosis-associated ovarian cancer patients and non-endometriosis-associated ovarian cancer patients. METHODS: This retrospective study included data of consecutive patients with endometrioid or clear cell ovarian cancer treated at the Fondazione IRCCS Istituto Nazionale dei Tumori di Milano between January 2010 and June 2021. Patients were assigned to one of two groups according to the absence or presence of endometriosis together with ovarian cancer at final histological examination. Survival outcomes were assessed using Kaplan-Meier and Cox hazard models. Proportions in recurrence rate and pattern of recurrence were evaluated using the Fisher exact test. RESULTS: Overall, 83 women were included in the endometriosis-associated ovarian cancer group and 144 in the non-endometriosis-associated ovarian cancer group, respectively. Patients included in the non- endometriosis-associated ovarian cancer group had a shorter disease-free survival than those in the endometriosis-associated ovarian cancer group (23.4 (range 2.0-168.9) vs 60.9 (range 4.0-287.8) months; p<0.001). Univariable and multivariable analyses showed that the association with endometriosis, previous hormonal treatment, early stage at presentation, and endometrioid histology were related to better disease-free survival in the entire study population. Similarly, patients in the non-endometriosis-associated ovarian cancer group had a shorter median (range) overall survival than those in the endometriosis-associated ovarian cancer group (54.4 (range 0.7-190.6) vs 77.6 (range 4.5-317.8) months; p<0.001). Univariable and multivariable analyses showed that younger age at diagnosis, association with endometriosis, and early stage at presentation were related to better overall survival. The recurrence rate was higher in the non-endometriosis-associated ovarian cancer group (63/144 women, 43.8%) than in the endometriosis-associated ovarian cancer group (17/83 women, 20.5%; p<0.001). CONCLUSIONS: Endometriosis-associated ovarian cancer patients had significantly longer disease-free survival and overall survival than non-endometriosis-associated ovarian cancer patients, while the recurrence rate was higher in non-endometriosis-associated ovarian cancer patients.

Sentinel lymph node biopsy in endometrial cancer: When, how and in which patients.

The role of nodal dissection in patients with endometrial cancer has been intensively studied in several studies. Historically, systematic pelvic and para-aortic lymphadenectomy represented the gold standard surgical treatment to assess potential nodal involvement and consequently define the appropriate stage of the tumor. Over the last years, sentinel node biopsy (SLNB) has been introduced as a more targeted alternative to lymph node dissection for lymph node staging and it has become popular among gynecologic oncologists. However, no level A evidence is still available, and several features of the SLNB technique have been matter of discussion among clinicians and a universally accepted methodology is still not currently available. This narrative review aims to summarize the body of knowledge on SLNB to offer the reader a complete picture about the evolution of this technique over the last decades.

Use of Sotrovimab in a cohort of pregnant women with a high risk of COVID 19 progression: a single-center experience.

Neutralizing monoclonal antibodies (mAbs) have been shown to reduce disease progression in patients with underlying predisposing conditions. Unfortunately, there is no evidence on the use of Sotrovimab in pregnant women. Herein we present a case series of pregnant women who received mAbs with Sotrovimab following the Italian Drug Agency (AIFA) indications. Since February 1, 2022 all pregnant women - regardless of gestational age - admitted to Obstetrics & Gynaecology of Policlinico University of Bari, with positive nasopharyngeal NAAT for SARS-CoV-2 were screened according to the AIFA indications for Sotrovimab and, if eligible, were proposed for treatment. Data on COVID-19, pregnancy, delivery, newborn outcomes, and adverse events were collected. From February 1 to May 15, 2022, 58 pregnant women were screened. Fifty (86%) patients were eligible, 19 of them (32.7%) denied their consent, in 18 cases (31%), the drug was temporarily unavailable, and the remaining 13 (22%) were treated with Sotrovimab. Out of these 13 patients, 6 (46%) were in the 3rd and 7 (54%) in the 2nd trimester of pregnancy. None of the 13 patients experienced adverse reactions due to Sotrovimab and all had a good clinical outcome. Furthermore, evaluating pre- and post-infusion clinical status and hematochemical profile, a reduction in D-dimers and an increase in SARS-CoV-2 antibodies (p < 0.01) during the 72 h following the infusion were observed. Our data, the first on the use of Sotrovimab in pregnant women, showed the safety and efficacy drug profile and its potential crucial role in preventing COVID-19 disease progression.

Radiomics and Molecular Classification in Endometrial Cancer (The ROME Study): A Step Forward to a Simplified Precision Medicine.

Molecular/genomic profiling is the most accurate method to assess prognosis of endometrial cancer patients. Radiomic profiling allows for the extraction of mineable high-dimensional data from clinical radiological images, thus providing noteworthy information regarding tumor tissues. Interestingly, the adoption of radiomics shows important results for screening, diagnosis and prognosis, across various radiological systems and oncologic specialties. The central hypothesis of the prospective trial is that combining radiomic features with molecular features might allow for the identification of various classes of risks for endometrial cancer, e.g., predicting unfavorable molecular/genomic profiling. The rationale for the proposed research is that once validated, radiomics applied to ultrasonographic images would be an effective, innovative and inexpensive method for tailoring operative and postoperative treatment modalities in endometrial cancer. Patients with newly diagnosed endometrial cancer will have ultrasonographic evaluation and radiomic analysis of the ultrasonographic images. We will correlate radiomic features with molecular/genomic profiling to classify prognosis.

Adverse Maternal Outcomes in Pregnant Women Affected by Severe-Critical COVID-19 Illness: Correlation with Vaccination Status in the Time of Different Viral Strains' Dominancy.

This is a monocentric and cross-sectional study conducted at the COVID-19 Division of the Obstetrical and Gynecological Unit and Intensive Care Units (ICUs) of Policlinico di Bari, in Bari, Italy, between September 2020 and April 2022. This study aimed to identify the prevalence of severe-critical COVID-19 illness requiring access to the Intensive Care Unit (ICU) among 287 pregnant patients, and possible correlations between the SARS-CoV-2 variants, the specific pandemic wave (dominated by wild, Alpha, Delta, and Omicron strains), and severe-critical adverse maternal outcomes. The prevalence of severe-critical COVID-19 illness was 2.8% (8/287), reaching 4.9% (8/163) excluding the 4th wave (Omicron dominant). The Delta variant determined the highest risk ratio and odds for access to the ICU due to severe-critical COVID-19-related symptoms compared to the other variants (wild, Alpha, Omicron). During the third wave (Delta), the ICU cases underwent a higher rate of hyperimmune plasma infusion (75%), antibiotic therapy (75%), and remdesivir (33%); all of the patients were intubated. During the Omicron wave, the patients were asymptomatic or with few symptoms: most of them (70%) were vaccinated with a median of two doses. The maternal outcome worsened in the case of Alpha and, especially, Delta variants for severe-critical COVID-19-related symptoms and ICU access.

Beyond BRCA1/2: Homologous Recombination Repair Genetic Profile in a Large Cohort of Apulian Ovarian Cancers.

BACKGROUND: Pathogenic variants in homologous recombination repair (HRR) genes other than BRCA1/2 have been associated with a high risk of ovarian cancer (OC). In current clinical practice, genetic testing is generally limited to BRCA1/2. Herein, we investigated the mutational status of both BRCA1/2 and 5 HRR genes in 69 unselected OC, evaluating the advantage of multigene panel testing in everyday clinical practice. METHODS: We analyzed 69 epithelial OC samples using an NGS custom multigene panel of the 5 HRR pathways genes, beyond the genetic screening routine of BRCA1/2 testing. RESULTS: Overall, 19 pathogenic variants (27.5%) were detected. The majority (21.7%) of patients displayed a deleterious mutation in BRCA1/2, whereas 5.8% harbored a pathogenic variant in one of the HRR genes. Additionally, there were 14 (20.3%) uncertain significant variants (VUS). The assessment of germline mutational status showed that a small number of variants (five) were not detected in the corresponding blood sample. Notably, we detected one BRIP1 and four BRCA1/2 deleterious variants in the low-grade serous and endometrioid histology OC, respectively. CONCLUSION: We demonstrate that using a multigene panel beyond BRCA1/2 improves the diagnostic yield in OC testing, and it could produce clinically relevant results.

Prognostic factors in clear cell carcinoma of endometrium: analysis of 55 cases.

BACKGROUND AND AIM OF THE WORK: The purpose of this study was to evaluate the clinical and pathologic prognostic factors associated with survival in patients with clear cell carcinoma (CCC) of the endometrium. METHODS: A retrospective review of fifty-five patients with endometrial clear cell carcinoma were collected. RESULTS: The median overall and disease-free survivals were 40 and 20 months, respectively. A univariate analysis was performed with respect to stage of disease, age, lymph nodes status, myometrium invasion, lymph vascular space invasion and adjuvant therapy. Stage was found to be the only important prognostic factor related to survival. In fact, early stage had a median survival of 77 months compared to 34 months in the advanced disease (p<0.04). These differences remained significant after adjusting for single stage (stage III versus IV).    Conclusions: Endometrial CCC is a rare histotype. Advanced stage disease is considered a poor prognostic factor. Recurrences are high even in early stage. Randomized clinical trials are needed.

Cross-Cultural Adaptation and Validation of the Italian Version of SWAL-QOL.

The aim of the study was to evaluate the reliability and validity of the Italian SWAL-QOL (I-SWAL-QOL). The study consisted of five phases: item generation, reliability analysis, normative data generation, validity analysis, and responsiveness analysis. The item generation phase followed the five-step, cross-cultural, adaptation process of translation and back-translation. A group of 92 dysphagic patients was enrolled for the internal consistency analysis. Seventy-eight patients completed the I-SWAL-QOL twice, 2 weeks apart, for test-retest reliability analysis. A group of 200 asymptomatic subjects completed the I-SWAL-QOL for normative data generation. I-SWAL-QOL scores obtained by both the group of dysphagic subjects and asymptomatic ones were compared for validity analysis. I-SWAL-QOL scores were correlated with SF-36 scores in 67 patients with dysphagia for concurrent validity analysis. Finally, I-SWAL-QOL scores obtained in a group of 30 dysphagic patients before and after successful rehabilitation treatment were compared for responsiveness analysis. All the enrolled patients managed to complete the I-SWAL-QOL without needing any assistance, within 20 min. Internal consistency was acceptable for all I-SWAL-QOL subscales (α > 0.70). Test-retest reliability was also satisfactory for all subscales (ICC > 0.7). A significant difference between the dysphagic group and the control group was found in all I-SWAL-QOL subscales (p < 0.05). Mild to moderate correlations between I-SWAL-QOL and SF-36 subscales were observed. I-SWAL-QOL scores obtained in the pre-treatment condition were significantly lower than those obtained after swallowing rehabilitation. I-SWAL-QOL is reliable, valid, responsive to changes in QOL, and recommended for clinical practice and outcome research.

Supracricoid partial laryngectomy: oncological and functional results.

PURPOSE: The purpose of this study was to evaluate the oncological and functional results of patients affected by laryngeal squamous cell carcinoma (SCC) and surgically treated by supracricoid partial laryngectomy (SCPL) at the ENT Department of the University Hospital of Ferrara. METHODS: In this retrospective study a total of 155 patients (149 males/l96.1% and 6 females/3.9%), have been included. All patients were treated between January 1st 1998 and December 31st 2010, by SCPL, including 126 cricohyoidopexies (CHP) and 29 cricohyoidoepiglottopexies (CHEP). RESULTS: The overall survival (OS) at 3 and 5 years was 88.77 and 83.24%, respectively and the disease-free survival (DFS) at 3 and 5 years was 84.4 and 81.55%, respectively.The recurrence rate was 17.5%, with local recurrences in 12.1% of the cases, regional in 4.7% and distant metastasis in 0.7% of the cases. Synchronous second primary tumors were 0.7% and metachronous second primary cancers (MSPCs) 5.4%. Removal of nasogastric feeding tube (NGT) or percutaneous endoscopic gastrostomy (PEG) was performed in 98.7% of the patients and lasted 22 days on average after SCPL (range 9-60), while decannulation was performed in all of patients at the 27th day on average after surgery. CONCLUSIONS: Oncological outcomes of this series are consistent with those of the literature, showing that SCPL is an effective and safe procedure in terms of survival rate and disease control. Functional outcomes confirmed that SCPL allows a good organ preservation and recovery of laryngeal functions.

Prognostic evaluation in supracricoid partial laryngectomy with cricohyoidopexy.

Identification of prognostic factors related to supracricoid partial laryngectomy may optimise indications for this surgical technique. We analysed several clinical and histopathological variables in a series of 81 patients treated with SPL at our department. Attention was focused on neoplastic spread of the anterior commissure, thyroid cartilage and prelaryngeal soft tissue of the neck. Statistical analysis (Kaplan-Meier method and Cox regression test) showed a significant decrease in survival for prelaryngeal soft tissue invasion. Due to the fact that the survival rate is not modified by the anterior commissure and thyroid cartilage infiltration, the prognostic value of prelaryngeal invasion is extremely relevant. Therefore, we suggest the oncological value of SPL even in cases of invasion of the anterior commissure or thyroid cartilage, but not beyond the outer perichondrium.

Supracricoid laryngectomy with cricohyoidopexy for recurrence of early-stage glottic carcinoma after irradiation. Long-term oncological and functional results.

CONCLUSIONS: These results suggest that, in selected cases, SCL-CHP may be used to treat laryngeal carcinomas after radiation failure, with good oncological and functional results. OBJECTIVES: Radiotherapy and surgery are believed to be equally effective and highly successful in the management of T1-staged glottic carcinomas. An almost normal post-therapy voice is considered the main advantage of irradiation over the surgical approach. On the other hand, when a tumour recurs after radiotherapy, it is more likely to extend beyond its original site, making total laryngectomy necessary in most cases. However, in selected cases, conservative laryngeal surgery is possible. At present only a few reports in the literature have documented the oncological and functional outcome of supracricoid laryngectomy with cricohyoidopexy (SCL-CHP) in the treatment of laryngeal recurrence after irradiation. MATERIAL AND METHODS: We describe seven cases of rT2-T3 laryngeal squamous cell carcinomas that recurred after radiotherapy and were treated with salvage SCL-CHP between 1989 and 1997 at the Department of Otolaryngology, University of Ferrara. The disease-free interval following initial radiotherapy ranged from 13 to 132 months (mean 54 months) in 6 patients; 1 patient underwent 2 courses of irradiation treatment 103 and 8 months prior to surgery. RESULTS: The mean post-SCL-CHP follow-up period exceeded 10 years (range 72-173 months). Only the patient who underwent 2 courses of radiation therapy before surgery experienced laryngeal recurrence 48 months after surgery. All patients were decannulated and recovered the ability to swallow. Vocal quality was significantly rough and breathy but was satisfactorily intelligible in all patients. Four patients had wound healing problems; 1 of them developed a laryngotracheocutaneous fistula 15 months after SCL-CHP as a consequence of chondronecrosis, prompting total laryngectomy.