Istituto Nazionale Dei Tumori Research Articles

Core competencies in palliative care among oncology nurses: An observational study

BACKGROUND: Palliative care requires a collaborative approach from a multidisciplinary team, incorporating nurses with ethical, clinical, communicative-relational, psychosocial, and teamwork skills. However, many professionals feel unprepared to face end-of-life challenges, highlighting a lack of skills, especially regarding psychosocial and spiritual aspects. AIM: The purpose of this study is to explore nurses' self-perception of competencies in palliative care. METHODS: A single-center descriptive observational study was conducted among palliative and non-palliative care nurses at the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan (INT), using the short Italian version of the Professional Competence Scale (PCSQ). The Kruskal-Wallis test was used along with multivariate ANOVA for statistical analysis. RESULTS: 122 nurses participated (response rate: 52%), predominantly women (78%), aged 25-34 (50%), with a degree (46%) and over 10 years of experience (41%). The majority had no experience (71%) in palliative care, while 16% were currently working in this field. Statistical analysis revealed no significant correlations between educational level and responses. The Kruskal-Wallis test showed that experience in palliative care significantly influenced self-assessment scores, such as in activating non-pharmacological management strategies (p=0.004). CONCLUSIONS: Nurses perceive high competence in ethical and clinical decision-making in palliative care, influenced more by experience than by training. Addressing patients' subjective needs and using non-pharmacological interventions remain a challenge for nurses not working in palliative care settings.

Gender Difference in sidE eFfects of ImmuNotherapy: a possible clue to optimize cancEr tReatment (G-DEFINER): study protocol of an observational prospective multicenter study.

Immune checkpoint inhibitors (ICIs) have significantly improved outcomes in various cancers. ICI treatment is associated with the incidence of immune-related adverse events (irAEs) which can affect any organ. Data on irAEs occurrence in relation to sex- differentiation and their association with gender-specific factors are limited. The primary objective of the G-DEFINER study is to compare the irAEs incidence in female and male patients who undergo ICI treatment. Secondary objectives are: to compare the irAEs incidence in pre- and postmenopausal female patients; to compare the irAEs incidence in female and male patients according to different clinical and gender-related factors (lifestyle, psychosocial, and behavioral factors). Exploratory objectives of the study are to compare and contrast hormonal, gene-expression, SNPs, cytokines, and gut microbiota profiles in relation to irAEs incidence in female and male patients. The patients are recruited from Fondazione IRCCS Istituto Nazionale dei Tumori, Italy, St Vincent's University Hospital, Ireland, Oslo University Hospital, Norway, and Karolinska Insitutet/Karolinska University Hospital, Sweden. The inclusion of patients was delayed due to the Covid pandemic, leading to a total of 250 patients recruited versus a planned number of 400 patients. Clinical and translational data will be analyzed. The expected outcomes are to improve the management of cancer patients treated with ICIs, leading to more personalized clinical approaches that consider potential toxicity profiles. The real world nature of the trial makes it highly applicable for timely irAEs diagnosis.

“Pelvic Neuro-Visualization: An Anatomical Illustration of the Autonomic Pelvic Nervous Network in Gynecologic Surgery”

ObjectiveDuring radical pelvic surgeries fibers of the autonomic pelvic nervous network can be accidentally damaged leading to significant visceral sequelae, which dramatically affect women's quality of life because of urinary, anorectal, and sexual postoperative dysfunctions.1,2 Direct visualization is one way to preserve hypogastric nerves (HNs), pelvic splanchnic nerves (PSNs), and the bladder branches from the inferior hypogastric plexus (IHP). However, the literature lacks critical photos and/or illustrations that are necessary to understand the precise anatomy needed to preserve the pelvic autonomic fibers. DesignNarrated laparoscopic video footage for identifying, dissecting, and preserving the autonomic nerve bundles during pelvic surgery. SettingTertiary level hospital—“IRCCS Istituto Nazionale dei Tumori”, Milano, Italy. InterventionsVisceral pelvic innervation is established by the superior hypogastric plexus(SHP) located anteriorly to the aortic bifurcation and the median sacral vessels and carries mostly sympathetic fibers. SHP divides in front of the sacrum into the right and left HN. At the level of the paracervix, the HNs join the parasympathetic PSNs coming out from sacral root S2, S3, S4 to form the IHP.2–5 Here, we performed laparoscopic surgery, before “Laparoscopic Approach to Cervical Cancer” trial (LACC) era, identifying key anatomic landmarks useful to highlight the path of the most commonly encountered autonomic pelvic nerves in gynecologic radical surgery: during the narration we describe and illustrate the procedure to identify all autonomic pelvic nerves, the sympathetic fibers, the PSNs, and the bladder branch emerging from the IHP in order to preserve their anatomic and functional integrity. This technique is anatomically and surgically indicated for adequate removal of the parametrical issues and vagina while preserving the total pelvic nervous system. ConclusionNerve-sparing surgery reduces bowel-, bladder- and sexual­ dysfunction without decreasing surgical efficacy.1,2 To accomplish safe and effective surgery, comprehension of the 3 dimensional structure of the vascular and nerve anatomy in the pelvis is essential. This video provides a great resource to educate surgeons, especially the youngest ones, about the retroperitoneal nervous networking: we identified the autonomic nerve pathway from adjacent tissues along the pathway consisting of cardinal, sacro-uterine, rectouterine/vaginal, and vesico-uterine ligaments.

Endometriosis-associated ovarian cancer: a different clinical entity

ObjectiveTo compare survival outcomes and patterns of recurrence between endometriosis-associated ovarian cancer patients and non-endometriosis-associated ovarian cancer patients.MethodsThis retrospective study included data of consecutive patients with endometrioid or clear cell...

Implementation of the e-IPOS in Home Palliative Cancer Care: A Quasiexperimental Pilot Study.

Electronic patient-reported outcome measures (e-PROMs) offer advantages in palliative cancer care, including rapid completion, improved data quality and direct storage, improving clinical decision-making. The electronic Integrated Palliative Care Outcome Scale (e-IPOS) in this context enables thorough self-assessment by patients, enhancing symptom management and self-reflection of their current situation. To evaluate the feasibility of implementing the e-IPOS in home palliative cancer care. The primary outcomes included the enrollment consent rate, study retention rate, e-IPOS completion rate and response completeness, and the number of clinical assessments and interventions performed during home visits. The secondary outcomes were the number of unscheduled visits and patients' perceived quality of life. A two-group quasiexperimental clinical pilot study. The control group received standard palliative care, the intervention group received standard care along with weekly e-IPOS completion during home visits. Both groups were enrolled for 4weeks. Adults with advanced cancer from the home palliative care unit of the Istituto Nazionale dei Tumori of Milan. Twenty-three patients were enrolled (74.19%), and 20 completed the study (drop-out: 13.04%). 82.5% of the expected e-IPOS responses were received, of which 96.9% were fully complete. In the intervention group, the Wilcoxon test showed an increase in identified needs and documented interventions (P < .05) and a decrease in unscheduled visits (P < .05). It is feasible to recruit people via home palliative care for an e-IPOS implementation study. Future fully powered studies should investigate the feasibility and assess patients' perceptions of its use to better understand its clinical benefits.

Soft tissue tumours of the penis. The 30-year Istituto Nazionale Tumori di Milano experience.

Small series and individual cases of penile soft tissue tumours are reported in the literature: these are rare tumours that represent less than 5% of all penile tumours. Penile soft tissue tumours were collected from the archive of the Department of Pathology at the Istituto Nazionale dei Tumori of Milan between January 1990 and October 2021. All available medical records were retrieved and reviewed to obtain clinical information. Our series refers to the 30-year experience of highlighting the heterogeneity in the presentation and microscopic features of these rare sarcomas. 18 penile soft tissue tumours are described, 4 benign and 14 malignant. The mean age at diagnosis was 58.2 years (range 24-96 years) and 53.6 years among malignancies (range 24-89). The most frequent histotype was Kaposi's sarcoma (nr = 4) and very unusual histotypes were observed, namely low-grade fibromyxoid sarcoma, synovial sarcoma, proximal type epithelioid sarcoma and the first reported case of dedifferentiated liposarcoma of the penis. Among sarcomas of the genitourinary tract, tumours of the soft tissues of the penis are the rarest. Penile sarcomas can present at a young age. Kaposi's sarcoma in HIV-negative patients has a favorable outcome, while deep sarcomas have an aggressive behavior and poor prognosis.

Exploring patient perspectives on electronic patient-reported outcome measures in home-based cancer palliative care: A qualitative study.

Electronic patient-reported outcomes (ePROMs) enhance symptom management and patients' engagement in palliative cancer care. However, integrating them into this setting brings challenges, including patients' familiarity with technological devices and declining health status. Prioritizing the patient's acceptability and feasibility is crucial for their adoption. However, more knowledge is needed about patients' perspectives on the adoption of ePROMs in the community, especially for home-based palliative care. Explore patient viewpoints on utilizing ePROMs for symptom reporting in home-based oncology palliative care. A qualitative interpretative approach was used to evaluate patients' points of view on using ePROMs in this specific care setting. Semistructured interviews were carried out. Data were analyzed using a reflexive thematic analysis. A total of 25 patients receiving oncological home palliative care from the advanced palliative care unit of the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, were invited to participate. Twenty interviews were conducted, as five patients declined due to deteriorating health. Four themes were identified: (1) strategic value of ePROMs and subjective appreciation; (2) enhancing patient centeredness through ePROMs; (3) exploring and addressing concerns about the use of ePROMs and (4) intersecting factors influencing the efficacy of ePROMs. Despite initial reticence, home palliative care patients consider ePROMs as potentially valuable allies monitoring symptoms, enhancing their quality of life, and amplifying their voices on less explored aspects of care. Continuous dialog between healthcare professionals and patients is crucial for addressing patient skepticism about ePROMs and their impact on the human aspect of care.

Protocol for the CHINT study: a cross-sectional observational study of risk factors for cancer and other non-communicable diseases in the Chinese community of Milan

IntroductionThe Chinese community in Italy is the largest in Europe. The area of Milan hosts the largest Chinese Italian community—about 41 000 people. Since little is known of the health...

Cancer patients’ needs for volunteer services during Covid-19: a mixed-method exploratory study

IntroductionTo date, there are no known studies that have investigated the new need for volunteer services among cancer patients during the Covid-19 pandemic. However, it is essential for volunteer associations to heighten such knowledge to best guide their offer in this challenging period.AimThe present study aims to provide a mapping of the cancer patients’ needs for volunteer services followed at Istituto Nazionale dei Tumori in Milan (Italy) during the Covid-19 pandemic. Since there are no specific questionnaires for this purpose, we created an ad hoc tool for which we report the preliminary result.MethodWe used a mixed-method multiphase approach. Phase I: in April-May 2020 40 ad hoc paper questionnaires were distributed at the entrance of the aforementioned hospital, with the aim of investigating patients’ needs through two open-ended questions then analyzed through thematic analysis. Phase II: the contents that emerged from Phase I were transformed into items and submitted to the judgment of a small group of “peers” (patients) and “experts” (professionals) in November-December 2020 to evaluate their comprehensiveness, representativeness and intrusiveness. Phase III: in January-February 2021 paper questionnaires, containing the items reviewed in Phase II, were distributed within the hospital to a representative sample of cancer patients. We applied descriptive statistics, Exploratory Factor Analysis (EFA) and Cronbach’s Alpha.Results32 patients completed Phase I, 3 “peers” and 9 “experts” participated in Phase II, 214 patients completed the questionnaire in Phase III. EFA highlights five kinds of needs during the Covid-19 pandemic, in order of priority: (1) need to be supported at the hospital; (2) need for emotional support; (3) need for daily errands; (4) need for practical support to family members; (5) need to share free time. Preliminary results on the tool are encouraging, although further studies are needed. These results will allow local volunteer associations to adapt their services during the pandemic.

I was only sixteen.

This short piece describes a new project developed by the adolescent patients with cancer involved in the Youth Project at the Istituto Nazionale dei Tumori in Milan, Italy. This is a scheme dedicated to young cancer patients with the dual aim of optimizing medical aspects of their care and promoting a holistic approach to their needs. "I was only sixteen" is a ballad, written in English by the patients, that became a song with the help of professional musicians (and among them international star Tony Hadley, former frontman of Spandau Ballet). This song sounds like hymn to life for teenagers with cancer in the world. It emphasizes again the value of giving young patients novel creative ways to express themselves.

Long-Term Survival Analysis of Pleural Mesothelioma Patients Undergoing Surgery: Brief Report From a Tertiary Referral Centre

Objectivesto date, no consensus has been reached on the surgical gold-standard in pleural mesothelioma (PM). We retrospectively reviewed our experience as a tertiary referral centre, to compare short- and long-term survival of PM patients undergoing different types of surgery. Methodsin retrospective, observational, single-centre study, we analysed all the patients histologically diagnosed with PM undergoing surgical procedures with palliative or curative intent at IRCCS Istituto Nazionale dei Tumori of Milan, Italy, from January 2003 to December 2020. The primary study endpoint was 10-year overall survival (OS) in three different types of resections: extra-pleural-pneumonectomy (EPP), pleurectomy/decortication (P/D), partial-pleurectomy/pleural-biopsy (PP/B). Secondary endpoints were postoperative hospital stay and postoperative 30-day and 90-day mortality rates. The survival function was estimated using Kaplan-Meier, and the Log-rank test was used for testing differences. Univariable and Multivariable Cox regression models were implemented to estimate Hazard Ratio (HR) for all variables of interest. Results243 consecutive patients were enrolled, EPP was performed in 49 (20.2%), P/D in 58 (23.8%), PP/B in 136 (56.0%) patients. The median follow-up time was 19.8 months. 10-year OS was significantly better for P/D group (16%, Log-Rank test p<0.0001) compared to PP/B (1.8%) and EPP (0%). No statistically significant differences were found among the 3 surgical groups in 30- and 90-day mortality rates. At multivariable analysis, gender (male, HR=1.58), type of resection (P/D, HR=0.55) and surgery date (recent years, HR=0.61) were found to be independent prognostic factors for OS. Conclusionsin PM, lung-sparing curative approach (e.g. P/D) should be preferred in highly selected patients and in highly experienced centres, whenever appropriate. Anyway, when P/D is not indicated, adopting palliative/conservative management (e.g. PP/B) could ensure comparable results as extremely aggressive surgeries (e.g. EPP). The aim of surgery in PM should not be reaching complete resection, but rather accomplishing significant resection allowing to complete the multimodality treatment in highly selected patients in experienced centers.

Mismatch Repair system protein deficiency as a resistance factor for locally advanced rectal adenocarcinoma patients receiving neoadjuvant chemo-radiotherapy.

Available data on Mismatch Repair system (MMR) deficiency are conflicting and derived from small studies. Our study aimed to evaluate the therapeutic implications of MMR status in patients with locally advanced rectal cancer (LARC). We retrospectively collected data from 318 patients affected by LARC treated in Italy at the Medical Oncology Units of the University Hospital of Cagliari, Istituto Nazionale dei Tumori Milan, and AOU Ospedali Riuniti Ancona. All patients underwent neoadjuvant chemoradiotherapy. The primary objective was major TRG while secondary objectives were pathological complete response, disease-free survival (DFS) and overall survival (OS). One hundred sixty patients (148 pMMR and 12 dMMR) were included in the exploratory cohort and 158 (146 pMMR and 12 dMMR) were included in the validation cohort. A major TRG has been shown in 42.6% and 43.1% patients with pMMR in exploratory and validation cohort, respectively; while no major TRG have been shown in dMMR patients in both cohorts. Exploratory and validation cohorts showed a statistically significant higher mDFS in pMMR patients compared to dMMR: NR vs. 14 months and NR vs. 17 months, respectively. Our results indicated an association between dMMR and poor response to preoperative chemoradiotherapy and they represent a hypothesis-generating data for new neoadjuvant strategies.

Assessing suffering of patients on cancer treatment and of those no longer treated using ESAS–Total Care (TC)

AimThe aim of the study was to assess the suffering of patients on oncologic treatment and of those no longer on treatment. Preliminarily, we aimed to confirm the psychometric properties of Edmonton Symptom Assessment System–Total Care (ESAS-TC) in different stages of the disease. The ESAS-TC screens physical and psychological symptoms, but also spiritual pain, discomfort deriving from financial problems associated with illness, and suffering related to social isolation.MethodsA sample of consecutive advanced cancer patients on oncologic therapies treated at the Internistic and Geriatric Supportive Care Unit (IGSCU) of Istituto Nazionale dei Tumori, Milano, and of terminal patients no longer on treatment and cared for by the Fondazione ANT palliative home care team were asked to fill the ESAS-TC. In order to strengthen the previous validation study of the ESAS-TC, 3-ULS (to assess social isolation), JSWBS (to assess spiritual well-being), COST-IT (to assess financial distress), and KPS (to assess functional status) were administered too.ResultsThe questionnaires were self-reported by 108 patients on treatment (52% >60 years old, female 53%, and 61% with KPS 90–100) and by 94 home care patients (71% >60 years old, female 51%, and 68% with KPS 10–50). The sound psychometric characteristics of ESAS-TC were confirmed. Patients on treatment showed lower total ESAS-TC score (19.3 vs 52.7, p<.001) after controlling for age and functional status, and lower financial distress (p.<001). Financial distress, spiritual suffering, and social isolation, after controlling for age, showed a significantly higher score in home care patients.ConclusionsOnly through an adequate routine assessment with validated tools is it possible to detect total suffering, the “Total pain” of patients, and treat it through a multidisciplinary approach. The study confirms the reliability and validity of the Italian version of ESAS-TC and the importance of supportive and early palliative care fully integrated with oncological treatment.

Adding fasting-mimicking diet to first-line carboplatin-based chemotherapy is associated with better overall survival in advanced triple-negative breast cancer patients: A subanalysis of the NCT03340935 trial.

Severe calorie restriction, in the form of cyclic fasting or fasting-mimicking diets (FMDs), boosts the antitumor activity of cytotoxic chemotherapy in mouse models of triple-negative breast cancer (TNBC). This effect is mostly mediated by fasting/FMD-induced reduction of plasma glucose concentration and by a boost in antitumor immunity. However, clinical evidence that cyclic FMD may impact on the outcomes of advanced TNBC (aTNBC) patients is lacking. We compared the overall survival (OS) of 14 aTNBC patients receiving first-line carboplatin-gemcitabine plus cyclic FMD in the context of the NCT03340935 trial with the OS of 76 consecutive aTNBC patients treated with carboplatin-based chemotherapy alone at Fondazione IRCCS Istituto Nazionale dei Tumori. Multivariable Cox regression models were used to adjust the prognostic impact of FMD for other prognostic variables. Patients undergoing cyclic FMD in combination with carboplatin-gemcitabine had better OS when compared to patients receiving chemotherapy alone (median OS 30.3 months, 95% CI 18-NR, vs 17.2 months, 95% CI 15.3-25.1, log-rank P value .041). Multivariable analysis confirmed an association between FMD use and better OS (HR: 0.40; 95% CI: 0.19-0.86; P = .019) also after propensity score-based matching according to patient ECOG PS and the presence of de novo metastatic disease (HR: 0.41; 95% CI: 0.21-0.83; P = .013). Cyclic FMD in combination with first-line chemotherapy may improve clinical outcomes in aTNBC patients. Our study paves the way for conducting phase II trials to investigate if cyclic FMD can increase the antitumor activity/efficacy of chemotherapy or chemoimmunotherapy in patients with early-stage TNBC or aTNBC.

Barriers and facilitators of electronic patient-reported outcome measures (e-PROMs) for patients in home palliative cancer care: a qualitative study of healthcare professionals’ perceptions

BackgroundPatient-reported outcomes in palliative care enable early monitoring and management of symptoms that most impact patients’ daily lives; however, there are several barriers to adopting electronic Patient-reported Outcome Measures (e-PROMs) in daily practice. This study explored the experiences of health care professionals (HCPs) regarding potential barriers and facilitators in implementing e-PROMs in palliative cancer care at home.MethodsThis was a qualitative descriptive study. The data were collected from two focus groups structured according to the conceptual framework of Grol. HCPs involved in home palliative cancer care of Fondazione IRCCS Istituto Nazionale dei Tumori of Milan were enrolled. Data were analyzed using a reflexive thematic analysis.ResultsA total of 245 codes were generated, 171 for the first focus group and 74 for the second focus group. The results were subdivided into subthemes according to Grol’s themes: Innovation, Individual professional, Patient, Social context, Organizational context, except Economic Political context. Nine HCPs attended the first focus group, and ten attended the second. According to these participants, e-PROMs could be integrated into clinical practice after adequate training and support of HCPs at all stages of implementation. They identified barriers, especially in the social and organizational contexts, due to the uniqueness of the oncological end-of-life setting and the intangible care interventions, as well as many facilitators for the innovation that these tools bring and for improved communication with the patient and the healthcare team.Conclusionse-PROMs are perceived by HCPs as adding value to patient care and their work; however, barriers remain especially related to the fragility of these patients, the adequacy of technological systems, lack of education, and the risk of low humanization of care.

Nonrestrictive diet does not increase infections during post-HSCT neutropenia: data from a multicenter randomized trial

AbstractInfections are a major cause of morbidity and mortality during neutropenia after hematopoietic stem cell transplantation (HSCT). The use of a low-microbial protective diet (PD) in the peritransplantation period is a standard of care, although its efficacy has never been tested prospectively. We conducted a multicenter, randomized, noninferiority trial, enrolling all consecutive adult patients undergoing high-dose induction chemotherapy or HSCT with the objective to compare nonrestrictive diet (NRD) vs PD. Overall, 222 patients were enrolled, randomly assigned, and analyzed. One hundred seventy-five subjects (79%) received autologous HSCT (auto-HSCT), 41 (18%) received allogeneic HSCT (allo-HSCT), and 6 (3%) patients received high-dose induction chemotherapy. There was no significant difference in terms of incidence of grade ≥2 infections and death during neutropenia in the 2 arms. In multivariable analysis, only multiple myeloma diagnosis, fluoroquinolone prophylaxis, and the absence of mucositis were associated with a lower incidence of grade ≥2 infections. We did not report any significant variation in terms of hospitalization length, incidence of mucositis and gastrointestinal infections, body weight, and serum albumin variations in the 2 arms. In allo-HSCT recipients, the incidence of acute graft-versus-host disease grade ≥3 was similar. NRD was associated with higher patient-reported satisfaction. In conclusion, NRD is not inferior to a traditional PD during neutropenia after HSCT, and our results demonstrated that implementing a restrictive diet unnecessary burdens patients' quality of life. The clinical trial was registered prospectively in the clinical trial registry of the Istituto Nazionale dei Tumori of Milan as INT54/16.

Real-time Fluorescent ICG and 99m-Tc Nanocolloid Tracer Navigation in Bilateral Sentinel Lymph Node Mapping of Vulvar Cancer

The effectiveness of sentinel lymph node (SLN) biopsy has been validated by two prospective trials, GROINS VI and GOG 1731-2. According to ESGO guideline in patients with unifocal tumors with a diameter of <4 cm, in the absence of suspected inguinal lymph nodes, SLN biopsy is recommended. The use of a radioactive tracer is mandatory.2 Using Indocyanine green (ICG) increase the detection of the vulvar sentinel node from 89.7 to 100%3. Aim of this video is to share our experience about the feasibility, safety and usefulness of the surgical identification of SLN in vulvar cancer using real-time fluorescent indocyanine green with 99m-technetium nanocolloid. Stepwise demonstration of the technique with narrated video footage. Tertiary level hospital "IRCCS Istituto Nazionale dei Tumori", Milano, Italy. A 50-year-old woman was diagnosed with vulvar cancer on biopsy of 1.5 cm size vulvar lesion under the clitoris area and referred to our Operative Unit. F-18 fluorodeoxyglucose positron-emission tomography-computed tomography (PET) showed no extra-vulvar disease. The patient was scheduled for radical vulvectomy and bilateral inguinal sentinel lymph-node biopsy (SLN). In this video the surgical procedure involved double location of SLN, first with the 99m-technetium detector followed by ICG identification. We used an ICG dilution of 2.5 mg/mL in sterile water and injected 4 mL around the tumor 5-10 min before visualization. First a handheld gamma probe used to identify the location of the SLN(s) with 99m-technetium. The fluorescence imaging was performed by the quest imaging system (FLUOPTICS©, Middenmeer, The Netherlands) that combine autofluorescence and fluorescence perfusion imaging. Second, we carried out the SLN biopsy using a dark mood procedure to identify the IGC tracer. The fluorescence imaging enables the detection of these markers through some millimeters of tissue and ICG has the advantage that is visible through the skin4. This video shows a successful combined 99m-technetium and ICG fluorescence image-guided bilateral SLN biopsy in a vulvar cancer patient using a near-infrared (NIR) optical imaging system (FLUOPTICS©). ICG for SLN mapping appears to be safe in women with vulvar cancer with a satisfactory detection rate. This may help in retaining surgical radicality while minimizing operative complications.

Real-world data on incidence of acute adverse reactions (AARs) reported in clinical practice.

e18814 Background: AARs are a significant concern in cancer treatment practice. The exact mechanisms underlying AARs are not fully understood. Their occurrence, even if rare, is unpredictable.This study updates the incidence of AARs in our large cohort of administrations as well as the impact on AARs of the increased number of targeted therapy drugs entered the clinical routine.Several new oncologic drugs have been rapidly developed in the last decade and many of them approved through a fast-track process.Medical Day Hospital of the Fondazione IRCCS Istituto Nazionale dei Tumori provides parenteral treatments for adult oncologic and hematological outpatients of the Medical Oncology Department, with a yearly average of 20,000 treatments, 25% of which are represented by investigational new drugs. Methods: A retrospective analysis of the AARs occurred between January 2020 and December 2022 was conducted.Overall, 61,096 treatments were performed. Therapeutic schemes included chemotherapies, targeted therapies, or both.Excluding the 14,667 investigational treatments, we analyzed 46,429 therapeutic regimens recorded in our database corresponding to 55,895 preparations of non-investigational drugs. Sixty % (33,580) of these preparations were chemotherapies and 40 % targeted therapies (22,315).All patients receiving chemotherapies were premedicated with steroids, while targeted therapies premedication was not always used.As part of the pharmacovigilance program, AARs occurring during injections of approved drugs were registered and reported to AIFA and Eudravigilance.It’s noteworthy that Covid-19 emergency interfered only marginally ( &lt; 10 %) with the amount of administrations performed during that period. Results: A total of 496 AARs out of 55,895 administrations were registered (0,9 %), of which 358 (72 %) were reported with chemotherapies and 138 (28 %) with targeted therapies.The great majority of AARs reported was not severe. Fourteen reactions ( 3% ) were classified as severe, six of them in the targeted therapy group.In order of frequency, among chemotherapies, reactions were more often associated with oxaliplatin, liposomal doxorubicin, etoposide, paclitaxel, vinflunin, docetaxel, cabazitaxel, fludarabine, cisplatin (relative incidence ≥ 1,5 %), while among targeted therapies with rituximab and isatuximab (2,5 % respectively) and TDM1, panitumumab, daratumumab, durvalumab (≥ 0,5 %). Conclusions: This single institutional study suggests useful informations to support safe management of current oncological treatments.Compared to published data, our findings show a low incidence of AARs.Better recognition of potential risk factors and recommendations about premedications, infusions rate and infusion reactions’ management could improve treatment outcome and healthcare drug delivery-related cost.

Mismatch Repair system protein deficiency as a factor of resistance to chemo-radiotherapy treatment in patients with locally advanced rectal adenocarcinoma and its influence on disease-free survival.

3615 Background: Available data on Mismatch Repair system deficit and microsatellite instability are conflicting and are generally derived from a small number of patients due to the rarity of this condition in rectal cancer. Our study aimed to evaluate the frequency and therapeutic implications of Mismatch Repair proteins (MMR) status in patients with locally advanced rectal cancer (LARC). Methods: We retrospectively collected data from 318 patients affected by LARC adenocarcinoma (cT3-4 +/- N1-2) treated at the Medical Oncology Unit of the University Hospital of Cagliari, Italy, the Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy and at the Medical Oncology Unit, AOU Ospedali Riuniti, Ancona. Italy. All patients included in the study underwent neoadjuvant concurrent capecitabine and long-course radiotherapy (RT) (total dose of Gy 50.4), afterwards a total mesorectal excision (TME) was performed. MMR expression was evaluated through immunohistochemistry. The primary objective was major TRG (0-1 Ryan’s score) while secondary objectives were pathological complete response, disease-free survival (DFS) and overall survival (OS). Results: 160 patients (148 pMMR and 12 dMMR) were included in exploratory cohort and 158 (146 pMMR and 12 dMMR) were included in validation cohort. A major TRG has been shown in 64/148 (42,6%) and 63/146 (43,1%) patients with pMMR in exploratory cohort and validation cohort, respectively; while no major TRG have been shown in dMMR patients in exploratory cohort nor in validation cohort. Both exploratory and validation cohorts showed a statistically significant higher median DFS in pMMR patients compared to dMMR ones: NR vs 14 months in exploratory cohort ( p = 0,003) and NR vs 17 months in validation cohort ( p = 0,02). Conclusions: Our retrospective study indicated an association between dMMR and poor or no response to preoperative chemoradiotherapy. These results are consistent with the role of MMR as a predictor of poor-response to chemoradiotherapy and represent a hypothesis-generating study for the selection of these patients for immunotherapy in the neoadjuvant setting, in which the available data are immature.

77P BRCA mutations may induce immune-resistance in breast cancer patients treated with IO-only approach: A retrospective analysis

Immunotherapy (IO) has been recently introduced in triple-negative breast cancer (TNBC) therapeutic algorithm, however no predictive biomarkers beyond PDL-1 expression demonstrated utility in clinical practice. BRCA mutations account for 15-20% of TNBC, with a positive association with platinum response and an inflammatory background on tumor tissue. Preclinical evidences demonstrated a lack of T-cell activation in BRCA-mutant (BRCAm) tumors due to an HLA machinery defects, but no subgroup effects were observed in IO pivotal trials evaluating chemotherapy-IO combinations. We retrospectively evaluated the effect of germline BRCA mutations in consecutive BC patients underwent any-line IO-only treatment in phase I/II trials at Fondazione IRCCS Istituto Nazionale dei Tumori in Milan. Only mutations evaluated as pathogenic after genetic counselling were considered. IO treatment included PD(L)1, LAG3 and ICOS inhibitors, single agents or in combination. Statistical analysis were performed with RStudio software v2022.07.0. Of 39 pts treated with IO from June 2016 to September 2022, 22 had available germline BRCA status. 4 pts exhibited mutations in BRCA1 gene, 1 in BRCA2. All pts had triple-negative histology, except one (HR+). Median number of previous treatment lines for metastatic disease was 2 (1-8), without significant difference among BRCA groups (p=0.872). None of the other clinical features evaluated significantly differ among BRCA groups. 18 (81.8%) patients received platinum compound as therapy for metastatic disease, while 4 (18.2) received a PARP inhibitor. BRCAm pts demonstrated a significantly shorted PFS compared to wild-type (1.7 vs 3.6 months; HR 4.12, CI 95% 1.32-12.89, p=0.015), whereas a non-significant trend toward a worse OS was observed in BRCAm pts (77.1 vs 42.0 months; HR 2.31, CI 95% 0.65-8.24, p=0.199). A numerically higher primary resistance rate was also observed in BRCAm pts (80% vs 50%). In our small retrospective cohort, the presence of a pathogenic mutation in BRCA1/2 genes resulted in reduced benefit to IO-alone approach. If confirmed in a wider and prospective cohort, these results could guide the decision on first-line treatment of BRCAm TNBC.