New Frontiers in the Treatment of Patients with HER2+ Cancer and Brain Metastases: Is Radiotherapy Always Useful?

Brain metastases (BM) pose a significant challenge in the management of HER2+ breast cancer since almost 50% of patients with HER2+ breast cancer develop brain tumors. The complex process of brain metastases involves genetic mutations, adaptations and mechanisms to overcome the blood-brain barrier. While radiotherapy is still fundamental in local therapy, its use is associated with cognitive adverse effects and limited long-term control, necessitating the exploration of alternative treatments. Targeted therapies, including tyrosine kinase inhibitors, monoclonal antibodies, and antibody-drug conjugates, offer promising options for HER2+ breast cancer patients with BM. Clinical trials have demonstrated the efficacy of these agents in controlling tumor growth and improving patient outcomes, posing the question of whether radiotherapy is always the unique choice in treating this cancer. Ongoing research into novel anti-HER2 antibodies and innovative combination therapies holds promise for advancing treatment outcomes and enhancing patient care in this clinical scenario. This narrative review provides a comprehensive overview of traditional medical treatments, molecularly targeted therapy and investigational agents in the management of HER2+ breast cancer with BM, highlighting the evolving landscape and potential future directions in treatment strategies to improve patient survival and quality of life.

Unveiling the Intricate Dance: How Cancer Orchestrates Muscle Wasting and Sarcopenia.

Sarcopenia is a prevalent and clinically significant condition, particularly among older age groups and those with chronic disease. Patients with cancer frequently suffer from sarcopenia and progressive loss of muscle mass, strength, and function. The complex interplay between cancer and its treatment, including medical therapy, radiotherapy, and surgery, significantly contributes to the onset and worsening of sarcopenia. Cancer induces muscle wasting through inflammatory processes, metabolic alterations, and hormonal imbalance. Moreover, medical and radiation therapies exert direct toxic effects on muscles, contributing to the impairment of physical function. Loss of appetite, malnutrition, and physical inactivity further exacerbate muscle wasting in cancer patients. Imaging techniques are the cornerstones for sarcopenia diagnosis. Magnetic resonance imaging, computed tomography, and dual-energy X-ray absorptiometry provide valuable insights into muscle structure and quality. Although each modality has advantages and limitations, magnetic resonance imaging produces high-resolution images and provides dynamic information about muscle function. Despite these challenges, addressing sarcopenia is essential for optimizing treatment outcomes and improving survival rates in patients with cancer. This review explored the factors contributing to sarcopenia in oncologic patients, emphasizing the importance of early detection and comprehensive management strategies.

Posterior Semicircular Canal Plugging Relieves Tumarkin's Crisis in Ménière's Disease Patients.

(1) Background: Patients affected by Ménière's disease can experience Tumarkin's syndrome, which is characterized by postural instability, gait abnormalities, and, occasionally, an abrupt loss of balance known as vestibular drop attack or Tumarkin's crisis. In this study, semicircular canal plugging is proposed as the definitive treatment for this condition. The outcomes of this type of surgery are discussed. (2) Methods: A total of 9 patients with a confirmed diagnosis of Ménière disease suffering from Tumarkin crisis underwent posterior semicircular canal plugging. These patients were assessed with Video Head Impulse Tests, vestibular evoked myogenic potentials, and Pure Tone Audiometry preoperatively and postoperatively. (3) Results: VHIT showed a postoperative decrease in PSC gain median (Preop. 0.86 and postop. 0.52; p < 0.009). No statistically significant differences were described for the anterior semicircular canal and the lateral semicircular canal. No patient experienced new Tumarkin crisis after the surgical treatment. (4) Conclusions: Our ten years of experience with posterior semicircular canal plugging in Ménière disease patients with Tumarkin's syndrome has shown that this type of surgical procedure is successful in controlling Tumarkin's crisis, with high patient satisfaction and little worsening in hearing level.

The Consistency and Quality of ChatGPT Responses Compared to Clinical Guidelines for Ovarian Cancer: A Delphi Approach.

INTRODUCTION: In recent years, generative Artificial Intelligence models, such as ChatGPT, have increasingly been utilized in healthcare. Despite acknowledging the high potential of AI models in terms of quick access to sources and formulating responses to a clinical question, the results obtained using these models still require validation through comparison with established clinical guidelines. This study compares the responses of the AI model to eight clinical questions with the Italian Association of Medical Oncology (AIOM) guidelines for ovarian cancer. MATERIALS AND METHODS: The authors used the Delphi method to evaluate responses from ChatGPT and the AIOM guidelines. An expert panel of healthcare professionals assessed responses based on clarity, consistency, comprehensiveness, usability, and quality using a five-point Likert scale. The GRADE methodology assessed the evidence quality and the recommendations' strength. RESULTS: A survey involving 14 physicians revealed that the AIOM guidelines consistently scored higher averages compared to the AI models, with a statistically significant difference. Post hoc tests showed that AIOM guidelines significantly differed from all AI models, with no significant difference among the AI models. CONCLUSIONS: While AI models can provide rapid responses, they must match established clinical guidelines regarding clarity, consistency, comprehensiveness, usability, and quality. These findings underscore the importance of relying on expert-developed guidelines in clinical decision-making and highlight potential areas for AI model improvement.

The Impact of Neoadjuvant Chemotherapy on Axillary Surgical Management of Patients With Breast Cancer and Positive Axillary Lymph Nodes.

BACKGROUND/AIM: Sentinel lymph node biopsy (SLNB) is effective in patients with breast cancer (BC) and positive axillary lymph nodes undergoing neoadjuvant chemotherapy (NAC). However, the frequency with which axillary lymphadenectomy (ALND) can be avoided remains debated. This study aimed to identify patient populations that can benefit from this approach. PATIENTS AND METHODS: The data of 195 consecutive patients with BC and positive axillary lymph nodes at diagnosis who underwent NAC were retrospectively analyzed. In all cases, the positivity of the lymph nodes was confirmed by cytological examination. Patients converted to ycN0 after NAC were considered eligible for SLNB. Indications for ALND were failed mapping, fewer than three SLNs recovered, and positive SLNs. RESULTS: Of 195 cN1 patients potentially eligible for SLNB, 71 (36.4%) remained clinically ycN+ after NAC and underwent elective ALND, while 124 (83.7%) converted to ycN0 after NAC and SLNB. The lymph node identification rate was 95.9% (119/124 patients) with three or more SLNs recovered in 83 cases (89.8%). One or two lymph nodes were recovered in 36 cases (30.2%). Nodal pathologic complete response (pCR) was found in 34/83 (40.9%) patients with three or more SLNs recovered. Considering all 195 patients initially included in the study, 55 patients (28.2%) achieved lymph node pCR after NAC. Nodal pCR varied based on hormone receptor and HER2 status, with rates ranging from 20.7% for ER+/HER2- patients to 95.3% for ER-/HER2+ patients (p<0.001). CONCLUSION: More than 80% of cN1 patients in our study were eligible for SLNB after NAC. ALND could be avoided in approximately 30% of cases, supporting the role of NAC in reducing the need for ALND among patients with lymph node metastases.

Abemaciclib pharmacology and interactions in the treatment of HR+/HER2- breast cancer: a critical review.

Abemaciclib (ABE) in combination with endocrine therapy represents the mainstay treatment for either endocrine-resistant metastatic or high-risk early-stage HR+/HER2- breast cancer patients. Hence, an adequate knowledge of this agent pharmacodynamic, pharmacokinetic, and of its drug-drug interactions (DDIs) is crucial for an optimal patients management. Additionally, ABE interference with food and complementary/alternative medicines should be taken into account in the clinical practice. Several online tools allow to freely check DDIs and can be easily consulted before prescribing ABE. According to one of this instruments, ABE display the lowest number of interactions among the available cyclin-dependent kinase 4/6 inhibitors. Still, clinicians should be aware that online tools cannot replace the technical datasheet of the drug as well as a comprehensive clinical assessment for each patient. Here we critically review the main pharmacological features of ABE, then focusing on its potential interactions with drugs, food, and alternative medicine, in order to provide a guide for its optimal use in the treatment of HR+/HER2- breast cancer patients.

Pharmacological features and drug interactions of abemaciclib Why was the review done? Abemaciclib, paired with hormone therapy, is a key treatment for breast cancer patients whose cancer cells respond to hormones but not to a protein called HER2. Understanding how this medication functions in the body, how it interacts with other drugs, and how the body processes it is crucial for providing optimal care. What did the authors do? The authors looked for published evidence about the way abemaciclib works into the body and about how it interacts with other drugs (including alternative medicines) or food. Then they summarized these findings. What did the authors find? Abemaciclib absorption, distribution, metabolism and excretion is well known and it is here described. What people eat and any alternative medications they take can affect how abemaciclib works. Online tools are available for doctors to check potential interactions between abemaciclib and other drugs a patient might be using. It's advisable for doctors to consult abemaciclib data sheet and use online tools before prescribing the drug. Notably, compared to similar treatments, abemaciclib has fewer interactions with other drugs. What does the review mean? This review delves into how abemaciclib works in the body and explore its potential interactions with other drugs, food, and alternative medicines. This information will aid doctors in using abemaciclib effectively for treating breast cancer patients.

Correlation between sentinel lymph node biopsy and non-sentinel lymph node metastasis in patients with cN0 breast carcinoma: comparison of invasive ductal carcinoma and invasive lobular carcinoma.

BACKGROUND: Some studies have suggested that axillary lymph node dissection (ALND) can be avoided in women with cN0 breast cancer with 1-2 positive sentinel nodes (SLNs). However, these studies included only a few patients with invasive lobular carcinoma (ILC), so the validity of omitting ALDN in these patients remains controversial. This study compared the frequency of non-sentinel lymph nodes (non-SLNs) metastases in ILC and invasive ductal carcinoma (IDC). MATERIALS METHODS: Data relating to a total of 2583 patients with infiltrating breast carcinoma operated at our institution between 2012 and 2023 were retrospectively analyzed: 2242 (86.8%) with IDC and 341 (13.2%) with ILC. We compared the incidence of metastasis to SLNs and non-SLNs between the ILC and IDC cohorts and examined factors that influenced non-SLNs metastasis. RESULTS: SLN biopsies were performed in 315 patients with ILC and 2018 patients with IDC. Metastases to the SLNs were found in 78/315 (24.8%) patients with ILC and in 460 (22.8%) patients with IDC (p = 0.31). The incidence of metastases to non-SLNs was significantly higher (p = 0.02) in ILC (52/78-66.7%) compared to IDC (207/460 - 45%). Multivariate analysis showed that ILC was the most influential predictive factor in predicting the presence of metastasis to non-SLNs. CONCLUSIONS: ILC cases have more non-SLNs metastases than IDC cases in SLN-positive patients. The ILC is essential for predicting non-SLN positivity in macro-metastases in the SLN. The option of omitting ALND in patients with ILC with 1-2 positive SLNs still requires further investigation.

Intraoperative Measurement of Insertion Speed in Cochlear Implant Surgery: A Preliminary Experience with Cochlear SmartNav.

OBJECTIVES: The objectives were to present the real-time estimated values of cochlear implant (CI) electrode insertion speed (IS) during intraoperative sessions using the Cochlear Nucleus SmartNav System to assess whether this measure affected CI outcomes and to determine whether real-time feedback assists expert surgeons in achieving slow insertion. METHODS: The IS was measured in 52 consecutive patients (65 implanted ears) using the CI632 electrode. The IS values were analyzed in relation to procedure repetition over time, NRT ratio, and CI audiological outcomes. RESULTS: The average IS was 0.64 mm/s (SD = 0.24); minimum and maximum values were 0.23 and 1.24 mm/s, respectively. The IS significantly decreased with each array insertion by the operator (p = 0.006), and the mean decreased by 24% between the first and last third of procedures; however, this reduction fell within the error range of SmartNav for IS (+/-0.48 mm/s). No correlation was found between IS and the NRT ratio (p = 0.51), pure-tone audiometry (PTA) at CI activation (p = 0.506), and PTA (p = 0.94) or word recognition score (p = 0.231) at last evaluation. CONCLUSIONS: The estimated IS reported by SmartNav did not result in a clinically significant reduction in insertion speed or an improvement in CI hearing outcomes. Real-time feedback of IS could potentially be used for training, but its effectiveness requires confirmation through additional studies and more accurate tools. Implementation of IS assessment in clinical practice will enable comparisons between measurement techniques and between manual and robot-assisted insertions. This will help define the optimal IS range to achieve better cochlear implant (CI) outcomes.

Polyps' Extension and Recurrence in Different Endotypes of Chronic Rhinosinusitis: A Series of 449 Consecutive Patients.

Different inflammatory endotypes reflect the heterogeneity of chronic rhinosinusitis with nasal polyps' (CRSwNPs) clinical presentation. This retrospective study aimed to analyze the distribution of polyps in nasal cavities and paranasal sinuses to establish a possible association between CRSwNP endotypes, prognosis, and polyps' extension. This study included 449 adult patients who underwent endoscopic sinus surgery for CRSwNPs between 2009 and 2022. Patients were categorized based on the number of paranasal sinuses involved by polyps. Statistical analyses, including Cox regression, were performed to identify associations between demographic, clinical, and histopathological factors and disease recurrence. CRSwNP patients were stratified into four groups based on the extent of polyp involvement. Asthma and acetylsalicylic acid (ASA) sensitivity were associated with more sinuses involved (p-values = 0.0003 and 0.0037, respectively). Blood eosinophil counts increased with the number of sinuses affected (p-value < 0.0001). The distribution of eosinophilic and non-eosinophilic histotypes varied significantly among these groups (p-value < 0.0001). The risk of CRSwNP recurrence was higher in patients with asthma, higher basophil percentages, and eosinophilic histotype (p-value 0.0104, 0.0001, 0.0118, and 0.0104, respectively). This study suggests a positive association between the number of paranasal sinuses involved by polyps and the severity of CRSwNPs, particularly in patients with eosinophilic histotype, asthma, and ASA sensitivity.

The Inheritance of Hearing Loss and Deafness: A Historical Perspective.

If the term "genetics" is a relatively recent proposition, introduced in 1905 by English biologist William Bateson, who rediscovered and spread in the scientific community Mendel's principles of inheritance, since the dawn of human civilization the influence of heredity has been recognized, especially in agricultural crops and animal breeding. And, later, in familial dynasties. In this concise review, we outline the evolution of the idea of hereditary hearing loss, up to the current knowledge of molecular genetics and epigenetics.

Bilateral simultaneous cochlear implants in children: Best timing of surgery and long-term auditory outcomes.

PURPOSE: Evaluate the hearing outcomes of bilateral deaf children implanted simultaneously and define the most appropriate timing for surgery. MATERIALS AND METHODS: Audiological CI results were retrieved in both the short-term and long-term period and compared by stratifying the patients into different subcohorts according to their age at surgery. Additional data collected were age at implant activation, etiology and timing of onset of deafness, presence of psychomotor delay. RESULTS: fifty-six bilaterally implanted children were included. The short-term outcomes differed significantly when comparing groups of different ages at implantation: younger patients achieved better aided pure tone audiometry results. Considering long-term follow-up, a significant correlation was identified between an early age at implantation and the hearing outcome at ages 2 to 5 years. Perceptive levels were better at 4 years of age in the younger group. No significant differences were found between children implanted at before 12 months and between 12 and 16 months of age. CONCLUSIONS: The results of the analyzed follow-up data support the hypothesis that children implanted at before 24 months are expected to have better hearing performances. Nevertheless, these results are referred to a widely heterogeneous group of patients and the duration of auditory deprivation should be considered.

A review and metanalysis of metronomic oral single-agent cyclophosphamide for treating advanced ovarian carcinoma in the era of precision medicine.

OBJECTIVE: Oral metronomic cyclophosphamide has been used as a single agent or in combination with other drugs for several solid tumors with interesting results in disease palliation and mild to moderate toxicity, notably in patients with recurrent epithelial ovarian cancer (EOC) progressing after systemic chemotherapy. In this paper, we report a review and a metanalysis of heterogeneous data published up to date. DATA SOURCES: The literature search was restricted to single-agent MOC. The analysis was conducted through March 2023 by consulting PubMed, Embase, Google Scholar, and The Cochrane Library databases. Research string and Medical Subject Headings included "ovarian tumor," "ovarian carcinoma," or "ovarian cancer," "fallopian tube cancer," "primary peritoneal cancer," "oral chemotherapy," and "metronomic cyclophosphamide." All articles were assessed for quality by at least two investigators independently, and a < 18 patients sample size cutoff was chosen as a lower limit with a Cohen's kappa statistical coefficient for accuracy and reliability. Metanalysis of selected papers was carried out according to a fixed model. DATA SUMMARY: The percentage of agreement between investigators on literature study selection was very high, reaching 96.9% with a Cohen's k of 0.929. MOC pooled objective response rate (ORR) and disease control rate for recurrent or platinum-refractory ovarian cancer were 18.8% (range 4-44%) and 36.2% (range 16-58.8%), respectively. The mean progressive-free survival and overall survival were 3.16 months (range 1.9 to 5.0 months) and 8.7 months (range 8 to 13 months), respectively. The fixed model metanalysis of selected studies showed a 16% median ORR (12-20% CI, p < 0.001). CONCLUSIONS: Single-agent oral cyclophosphamide in EOC holds promise as a treatment option, even in the era of precision medicine. Genetic factors, such as DNA repair gene polymorphisms, may influence treatment response. Combining cyclophosphamide with biological agents such as PARP inhibitors or immunotherapy agents is an area of active investigation.

Exploring the Potential of Non-Coding RNAs as Liquid Biopsy Biomarkers for Lung Cancer Screening: A Literature Review.

Lung cancer represent the leading cause of cancer mortality, so several efforts have been focused on the development of a screening program. To address the issue of high overdiagnosis and false positive rates associated to LDCT-based screening, there is a need for new diagnostic biomarkers, with liquid biopsy ncRNAs detection emerging as a promising approach. In this scenario, this work provides an updated summary of the literature evidence about the role of non-coding RNAs in lung cancer screening. A literature search on PubMed was performed including studies which investigated liquid biopsy non-coding RNAs biomarker lung cancer patients and a control cohort. Micro RNAs were the most widely studied biomarkers in this setting but some preliminary evidence was found also for other non-coding RNAs, suggesting that a multi-biomarker based liquid biopsy approach could enhance their efficacy in the screening context. However, further studies are needed in order to optimize detection techniques as well as diagnostic accuracy before introducing novel biomarkers in the early diagnosis setting.

Real-world ANASTASE study of atezolizumab+nab-paclitaxel as first-line treatment of PD-L1-positive metastatic triple-negative breast cancer.

The combination of atezolizumab and nab-paclitaxel is recommended in the EU as first-line treatment for PD-L1-positive metastatic triple-negative breast cancer (mTNBC), based on the results of phase III IMpassion130 trial. However, 'real-world' data on this combination are limited. The ANASTASE study (NCT05609903) collected data on atezolizumab plus nab-paclitaxel in PD-L1-positive mTNBC patients enrolled in the Italian Compassionate Use Program. A retrospective analysis was conducted in 29 Italian oncology centers among patients who completed at least one cycle of treatment. Data from 52 patients were gathered. Among them, 21.1% presented de novo stage IV; 78.8% previously received (neo)adjuvant treatment; 55.8% patients had only one site of metastasis; median number of treatment cycles was five (IQR: 3-8); objective response rate was 42.3% (95% CI: 28.9-55.7%). The median time-to-treatment discontinuation was 5 months (95% CI: 2.8-7.1); clinical benefit at 12 months was 45.8%. The median duration of response was 12.7 months (95% CI: 4.1-21.4). At a median follow-up of 20 months, the median progression-free survival was 6.3 months (95% CI: 3.9-8.7) and the median time to next treatment or death was 8.1 months (95% CI: 5.5-10.7). At 12 months and 24 months, the overall survival rates were 66.3% and 49.1%, respectively. The most common immune-related adverse events included rash (23.1%), hepatitis (11.5%), thyroiditis (11.5%) and pneumonia (9.6%). Within the ANASTASE study, patients with PD-L1-positive mTNBC treated with first-line atezolizumab plus nab-paclitaxel achieved PFS and ORR similar to those reported in the IMpassion130 study, with no unexpected adverse events.

Ultra-Early Treatment of Neurosurgical Emergencies with Endoscopic Endonasal Approach: Experience from Three Italian Referral Centers.

PURPOSE: the aim of this multicenter study is to preliminarily assess the role of the Endoscopic Endonasal Approach (EEA) in ultra-early (i.e., within 12 h) management of selected neurosurgical emergencies in terms of clinical and radiological outcomes. METHODS: 26 patients affected by sellar/parasellar pathologies with rapid progression of symptoms were managed with EEA within 12 h from diagnosis in three Italian tertiary referral Centers from January 2016 to December 2019. Both clinical and radiological data have been collected preoperatively as well as post-operatively in order to perform retrospective analysis. RESULTS: The average time from admission to the operating room was 5.5 h (±2.3). The extent of resection was gross-total in 20 (76.9%), subtotal in 6 (23.1%) patients. One patient experienced re-bleeding after a subtotal removal of a hemorrhagic lesion. Patients with a longer time from admission (>4 h) to the operatory room (OR) experienced stable impairment of the visual acuity (p = 0.033) and visual field (p = 0.029) in the post-operative setting. CONCLUSIONS: The Endoscopic Endonasal Approach represents a safe, effective technique that can be efficiently used with good results in the management of selected neurosurgical emergencies in centers with adequate experience.

Outcomes of Sentinel Lymph Node Biopsy for Patients With Node-positive Breast Cancer Treated With Neoadjuvant Chemotherapy.

BACKGROUND/AIM: Clinical trials have shown that the sentinel lymph node biopsy (SLNB) is feasible for patients with cN1 breast carcinoma treated with neoadjuvant chemotherapy (NAC). This study aimed to evaluate the technical outcomes of SLNB by assessing the volume of residual nodal disease. PATIENTS AND METHODS: All patients with cT1-3 cN1 breast cancer undergoing NAC from January 2018 to December 2021 were retrospectively identified from our institutional database. We assessed the outcomes of preoperative clinical examination, ultrasonography, and other imaging to predict the axillary nodal status after NAC for patients converted to cN0 and undergoing SLNB; both adequate mapping and false-negative rate (FNR) at intraoperative evaluation of SLN were assessed. RESULTS: Overall 160 patients were included in the study; 98 were converted to cN0 and underwent SLNB. No difference was found in the adequate mapping rate nor in the mean number of SLNs retrieved compared to the residual LN burden. The intraoperative SLN FNR was 38.2%, with smaller nodal volume being associated with lower FNR (p<0.01). The positive predictive values of physical examination and imaging-based nodal assessment post-NAC were 87.1% and 68.2%, respectively. CONCLUSION: In a significant percentage of patients with cN1 disease converted to cN0 after NAC, it was possible to recover three or more SLNs. The residual volume of LN disease did not impact the SLN mapping rate. However, we found a high FNR for intraoperative SLN evaluation, particularly for patients with small residual nodal disease. It seems that only a small proportion of patients eligible for SLNB after NAC can be spared ALND.

Hearing Aid in Vestibular-Schwannoma-Related Hearing Loss: A Review.

(1) Background: Several types of hearing aids are available for the rehabilitation of vestibular-schwannoma (VS)-related hearing loss. There is a lack of recently published papers regarding this theme. The aim of the present work is to organize current knowledge. (2) Methods: A review of the literature regarding the topics "vestibular schwannoma", "hearing loss", and "hearing aid" was performed. Nineteen studies were thus considered. (3) Results: Conventional hearing aids, contralateral routing of signal (CROS) aids, bone anchored hearing aids (BAHA), and others are available options for hearing rehabilitation in VS patients. The speech discrimination score (SDS) is considered the best measure to assess candidacy for rehabilitation with hearing aids. The best hearing rehabilitative conditions in VS patients when using conventional hearing aid devices are a mild-moderate hearing loss degree with good word recognition (more than 50% SDS). CROS-Aid and BAHA are reported to be beneficial. CROS-Aid expands on the area of receiving hearing. BAHA aids use direct bone-conduction stimulation. Unfortunately, there are no available studies focused specifically on VS patients that compare CROS and BAHA technologies. (4) Conclusions: Hearing aids, CROS, and BAHA are viable options for rehabilitating hearing impairment in VS, but require an accurate case-by-case audiological evaluation for rehabilitating hearing impairment in VS. Further studies are needed to prove if what is currently known about similar hearing illnesses can be confirmed, particularly in the case of VS.

A retrospective, real-life analysis of metronomic oral single-agent cyclophosphamide for the treatment of platinum-pretreated advanced ovarian carcinoma in Italy.

INTRODUCTION: Metronomic oral cyclophosphamide (MOC) presents many potential advantages, such as significantly less severe side effects than standard regimens, ease of administration, and the delivery of a dose-dense but not necessarily dose-intense treatment. These observations prompted us to evaluate in a retrospective, multicenter study the efficacy and toxicity of MOC in a real-life series of pretreated cancer patients. METHODS: The study is a multicenter, retrospective analysis of the activity of single-agent MOC in patients with recurrent or residual epithelial ovarian, fallopian tube, or primary. Eligible patients were continuously treated with MOC at 50 mg/day until progression, toxicity, or death. Overall response rate (ORR), stable disease (SD), and disease control rate (DCR) were reported. RESULTS: The study included 62 patients. Three patients reached a complete response rate (5%), 11 had a partial response rate (18), and 15 had stabilization of disease (24) for an ORR of 23% and a DCR of 47%. Patients with low-grade indolent tumors showed an ORR and an SD rate higher than that observed in non-indolent ones (33% vs. 18% and 28% vs. 14%, respectively). Overall, progression-free survival was 3.5 months (range 1-9 months). CONCLUSION: Single-agent MOC is active and very well tolerated in a significant fraction of patients with refractory, recurrent, or residual epithelial ovarian, fallopian tube, or primary peritoneal cancer. In the vision of a practical approach, single-agent MOC may be a useful palliative treatment option for patients with poor tolerance to high-dose regimens or widely pretreated. Further studies are needed better to characterize the role of such an approach in clinical practice.