Institute Of Oncology Research Articles

The Multidisciplinary Approach in Stage III Non-Small Cell Lung Cancer over Ten Years: From Radiation Therapy Optimisation to Innovative Systemic Treatments.

Background: About 30% of new non-small cell lung cancer (NSCLC) cases are diagnosed at a locally advanced stage, which includes a highly heterogeneous group of patients with a wide spectrum of treatment options. The management of stage III NSCLC involves a multidisciplinary team, adequate staging, and a careful patient selection for surgery or radiation therapy integrated with systemic treatment. Methods: This is a single-center observational retrospective and prospective study including a consecutive series of stage III NSCLC patients who were referred to the Veneto Institute of Oncology and University Hospital of Padova (Italy) between 2012 and 2021. We described clinico-pathological characteristics, therapeutic pathways, and treatment responses in terms of radiological response in the entire study population and in terms of pathological response in patients who underwent surgery after induction therapy. Furthermore, we analysed survival outcomes in terms of relapse-free survival (RFS) and overall survival (OS). Results: A total of 301 patients were included. The majority of patients received surgical multimodality treatment (n = 223, 74.1%), while the remaining patients (n = 78, 25.9%) underwent definitive CRT followed or not by durvalumab as consolidation therapy. At data cut-off, 188 patients (62.5%) relapsed and the median RFS (mRFS) of the entire population was 18.2 months (95% CI: 15.83−20.57). At the time of analyses 140 patients (46.5%) were alive and the median OS (mOS) was 44.7 months (95% CI: 38.4−51.0). A statistically significant difference both in mRFS (p = 0.002) and in mOS (p < 0.001) was observed according to the therapeutic pathway in the entire population, and selecting patients treated after 2018, a significant difference in mRFS (p = 0.006) and mOS (p < 0.001) was observed according to treatment modality. Furthermore, considering only patients diagnosed with stage IIIB-C (N = 131, 43.5%), there were significant differences both in mRFS (p = 0.047) and in mOS (p = 0.022) as per the treatment algorithm. The mRFS of the unresectable population was 16.3 months (95% CI: 11.48−21.12), with a significant difference among subgroups (p = 0.030) in favour of patients who underwent the PACIFIC-regimen; while the mOS was 46.5 months (95% CI: 26.46−66.65), with a significant difference between two subgroups (p = 0.003) in favour of consolidation immunotherapy. Conclusions: Our work provides insights into the management and the survival outcomes of stage III NSCLC over about 10 years. We found that the choice of radical treatment impacts on outcome, thus suggesting the importance of appropriate staging at diagnosis, patient selection, and of the multidisciplinary approach in the decision-making process. Our results confirmed that the PACIFIC trial and the following introduction of durvalumab as consolidation treatment may be considered as a turning point for several improvements in the diagnostic-therapeutic pathway of stage III NSCLC patients.

A study on prevalence of psychiatric morbidity in advanced breast cancer patients at a tertiary cancer hospital in South India

Breast cancer is one of the most common cancers among women globally as well in India. Breast cancer patients may suffer from psychological morbidity. Psychological problems like depression, anxiety, may affect the quality of life of breast cancer patients. To study the psychiatric morbidity in diagnosed advanced breast cancer patients.A cross sectional study was done in the department of Psychiatry, over a period of one and half years from January 2014 to June 2015 at Osmania Medical College Allied Hospitals (M.N.J Institute of Oncology &amp; Regional Cancer Centre and Osmania General Hospital), Hyderabad, Telangana. Breast cancer patient cases and controls were studied by the General health questionnaire -28 (GHQ-28)Mini International Neuropsychiatric Interview- plus (mini- plus).This difference in the proportion of psychiatric disorders was statistically significant.By using MINI plus, 26.7% of breast cancer patients reported psychiatric illness and this percentage was 10% in controls. This difference was not statistically significant at p value of 0.05 (Chi square value 2.78, p value 0.18). The most common psychiatric morbidities were Dysthymia, and MDD seen in 3 (10%) women each.Adjustment disorder unspecified was found in 2 (6.7%) women. There are statistically significant differences between cases and controls and these differences are circumscribed to domains of recall and language and orientation. The mean total score obtained by cases is 28.60 with a standard deviation of 1.354 and that obtained by the control group is 29.70 with a standard deviation of 0.535. The difference between the two groups is highly significant (p&amp;#60;0.001).The study brings out the need for identifying psychiatric problems at proper time, referral of breast cancer patients to Psychiatrists and points out the need for establishing psychiatric units in Cancer Institutes.

Real-Life Experience of Use of Venetoclax in Patients with Relapsed/Refractory Acute Myeloid Leukemia. a Single Center Experience

INTRODUCTION: Venetoclax (VEN), a BCL-2 specific inhibitor, used in combination with azacitidine (AZA) in patients with newly-diagnosed acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy treatment, has shown high response rate and overall survival compared with AZA monotherapy (Di Nardo et al. N Engl J Med 2020; 383:617-629). For patients failing frontline, VEN-based salvage therapy prognosis appears very poor, although a subgroup of patients might benefit. Moreover, recently, had been published the European LeukemiaNet 2022 recommendations and classification in AML (Döhner et al. Blood 2022). AIMS: We performed a retrospective study of patients with relapsed/refractory (R/R) AML receiving salvage treatment with VEN combinations in the Catalan Institute of Oncology (ICO) in order to determine the efficacy and safety of the combination. We also explored the probability of response according to the ELN 2022 risk classification by genetics. METHODS: We analyze 60 patients with R/R AML at 4 hospitals belonging to ICO in Spain, treated with VEN (400mg/24h or 600mg/24h; with recommended 3-day ramp-up to target dose) in combination with hypomethylating (HMA) agents (AZA 75mg/m2 7/28 days or Decitabine (DEC) 20mg/m2 5/28 days) or low-dose cytarabine (LDAC) (20mg/m2 10/28 days) from May 2019 until December 2021. Event was defined as death, refractoriness to treatment or progressive disease. RESULTS: Characteristics of our cohort are described in table 1. Thirty-seven (62%) patients had next-generation sequencing (NGS) panel study at diagnosis and/or at the time of R/R disease. 31 (52%) patients had high-risk AML according to ELN 2017 classification, and 38 of 46 (83%) patients had high-risk AML according to ELN 2022 classification. Six of 37 patients (15%) had TP53 mutation at a variant allele fraction (VAF) of at least 10%. Seven (19%) patients were reclassified as high-risk AML according to ELN 2022 classification. NGS panel study didn't show high risk mutations in 10 patients. According to ELN 2022 classification, 8, 11 and 8 patients, presented 1, 2 or ≥ 3 high risk gene mutations, respectively. Fourteen (23%) patients received VEN + DEC, 34 (57%) VEN + AZA, and 12 (20%) VEN + LDAC. The median number of cycles received was 3 (range 1-28), with a median of one cycle to achieve the best response (range: 1-4). Early mortality in the first 30 days was 15% (9 patients), 5 due to progression disease, 2 due to infection and 2 due to clinical worsening. Overall response rate after first cycle [Complete response (CR) + complete response without hematological recovery (CRi) and partial response (PR)] was 58%. Three patients were treated in a molecular relapse (MRD positive status), and all of them achieved molecular response. Six of 19 fit young patients (32%) achieved CR and received an allogeneic stem cell transplantation (alloSCT). The median event-free survival (EFS) and overall survival (OS) was 4.03 months and 7.63 months, respectively. No significant differences of EFS and OS were found according to ELN 2022 risk classification, mutational profile or TP53 status. Response to treatment after 3-4 cycles, discriminate two groups of patients with an OS of 17.26 months in those patients who achieved CR or PR vs 2.4 months in non-responders (p=0.000). Patients relapsed after alloSCT (7 patients) presented a poor outcome (median OS was 1.6 months). SUMMARY/CONCLUSIONS: Our study showed that real-world experience of treating patients with R/R AML with VEN + HMA or LDAC is feasible as salvage treatment in patients relapsed to HMA and as bridge therapy to alloSCT with a rapid response rate. No significant differences of response were found according to ELN 2022 risk classification. Rapid responses shown with the combination, allow us to identify those patients who may benefit from this approach. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Management of Patients with Treatment-Free Remission in Chronic Myeloid Leukemia

Background: Chronic myeloid leukemia (CML) is a relatively common BCR-ABL-positive chronic myeloproliferative neoplasm within the structure of morbidity by hematological malignancies with primary bone marrow (BM) involvement, being characterized in the advanced phases by a relapsing evolution, sizable disease burden, unfavorable socio-economic impact and poor prognosis. Tyrosine kinase inhibitors (TKIs) have improved fundamentally the treatment outcomes in CML, bringing the patients' life expectancy closer to that of the general population. Nevertheless, TKI discontinuation studies indicate discordance in the incidence of hematological and molecular relapses. Objectives: The aim of the study was to evaluate the short- and long-term outcomes of treatment discontinuation in CML patients with complete molecular response (CMR). Material and methods: This prospective study included 22 patients with chronic phase of CML, treated and followed up at the Oncologic Institute from Moldova between 2017-2022. The age range was 29-73 years (average age - 45.8 years). The male/female ratio was 1:1.2. The quantitative reverse transcription polymerase chain reaction (PCR) was performed in order to determine the expression of the BCR-ABL p210 and p190 transcripts. Five transcription products (b2a2, b3a2, b2a3, b3a3 si e1a2) were analyzed by the usage of the PCR test. The real-time quantitative PCR revealed the wide range of BCR-ABL p210 transcript: 21.84-100% IS. In 7 (31.8%) cases the initial rate of BCR-ABL p210-positive cells was less than 50%. Only 2 (9.0%) patients also proved to be positive for BCR-ABL p190 transcript. Results: CMR was obtained in 15 (68.2%) patients after imatinib therapy and in 7 (31.8%) patients after therapy with 2nd TKIs generation. The therapy with TKIs was stopped due to the different reasons in all patients after the achievement of CMR. Two (9.1%) patients discontinued the TKIs treatment due to the pregnancy. The molecular relapse occurred in 6 (27.3%) pts, including one pregnant female. There were no subsequent hematological relapses. All patients with molecular relapse had the initial BCR-ABL p210 transcript expression > 50%. One (4.5%) of them was positive for BCR-ABL p190 transcript at diagnosis. The CMR span ranged between 2.5-26 months in relapsed patients. The range of BCR-ABL p210 transcript in the relapsed cases was 0.002-0.56%. These patients attained the 2nd CMR after resuming the treatment with the same or higher TKIs generation. In 2 (9.0%) pregnant females the pregnancy resulted in the healthy newborns. One (4.5%) female with a history of lymphoblastic type of acute phase experienced the minor molecular relapse (BCR-ABL p210 transcript - 0.56%), and reobtained the CMR after restarting imatinib mesylate. The relapsed patients did not develop the 2nd molecular relapse. All patients are alive, with the ECOG-WHO score of 0-1. Conclusions: TKIs stopping proved to be a reliable management option in CML patients with chronic phase, CMR and low BCR-ABL p210 transcript expression at diagnosis. The stable 2nd CMR may be achieved after resuming the TKIs treatment at a higher dosage or generation in patients with minor molecular relapse. Pregnancy may not influence the molecular relapse rate after TKIs discontinuation and its curability.

A Successful Patient Blood Management System Implemented during the COVID Pandemic Based on Daily Blood Inventory Levels in a Single Large Oncology Institution

Introduction: The recent pandemic brought to light the fragility of the US Blood Collection system and supply chain disruption. As blood donations declined, blood donor centers (BDC) and blood banks (BB) worldwide reported a significant blood shortage. Our blood donor center had challenges from imposed COVID precautions (social distancing, contact restrictions, donations by appointments only, wearing of PPEs, etc.) to increase blood collections to replace the units transfused daily. The study was to review our Institutional process for development of Covid-19 risk levels-based dashboards which tracked the pandemic and provided risk levels in real time to faulty/staff employees. Methods: As the Blood Inventory decreased daily during the start of the pandemic and ultimately became critical, the Transfusion Service/Blood Bank (TS/BB) would reset and lower the triage Hgb level from 7.0 gm/dl to 8.0 gm/dL based on O pRBC units in inventory. The challenge was to disseminate the blood inventory to all stakeholders, decrease the number of calls/pages to TS/BB/Transfusion Medicine Physician (TMP) on call and be consistent in setting Hgb triage levels. Surgery/Anesthesia required daily inventory to predict cases that would have to be cancelled and rescheduled for possible increased estimated blood loss. As the national/local blood supply shortage became critical especially for O RBC Units, a Blood Shortage Decision Matrix was created in collaboration with our Chief Patient Safety Officer, Chief Administrative Quality Officer and Chief Information Technology Officer teams with a color-coded legend (RED - Hgb <=7.0 gm/dL [Emergencies only], ORANGE- Hgb <=7.0 gm/dL, YELLOW -Hgb <=7.5 gm/dL and GREEN <=Hgb 8.0 gm/dL) illustrating how blood would be triaged based on the O red cells units available in Inventory for transfusion each day (See Table ). Minimal/critical numbers for each blood product/blood group were derived based on logistic regression/machine learning/manual counts from historic usage within the past 2 years. A similar color-coded diagram was used for Platelet Inventory. The blood inventory continues to be reported at the daily morning Department/Divisional (Operations) Tier Readiness Briefings (Institution's Pathway leading to a High reliability Organization) for institution wide dissemination. The TS/BB Information System is linked to real time blood inventory of all blood products entered into the system and provided us with real time inventory except for units that required a second ABO Rh and irradiation. Computer queries were performed for the latest inventory by blood product available and received, total number of Inpatient and Emergency Medicine patients by blood types and their latest hemoglobin values with transfusion orders and transfused currently, patients who were not transfused currently with no active orders and patients who were transfused since last day of transfusion by blood types. Supply Estimates were made for blood products from donors collected at our BDC and blood products that would have to be purchased from outside suppliers. This was to guide decision making for both the BDC to provide blood products to the TS/BB and for the TS/BB to assess how many products needed to be ordered from outside suppliers. Demand estimates were made from historical data, current inpatient census from the EMR inpatient dashboard, number of current inpatients (ICU, Hematologic Oncology, Acute Cancer Care Center etc.) who were O pos (Per Webi query with a real time report run each morning), by location, blood type, hemoglobin level and days since latest hemoglobin level. Data was used to assess how many of the patient groups already met hemoglobin levels designed by the color code chart described above between 7.0 and 8.0 gm/dL which assisted the TS/BB to triage pRBC orders based on Hgb levels set for the colors. Results: The Blood Shortage Decision Matrix since its implementation in October 2021 has allowed clear organizational-wide ownership across all levels of the organization, use of a standardized Blood Inventory management by the TS/BB, improved communications with primary care teams, better understanding of the challenges maintaining an adequate blood supply by the Executive/Administrative Leadership leading to allocation of additional needed resources to the Blood Donor Center/TS/BB and also helps the Institution on its path toward a High reliability Organization. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

BIOM-19. NEXT-GENERATION SEQUENCING (NGS) FOR IDENTIFYING ACTIONABLE MOLECULAR ALTERATIONS IN NEWLY DIAGNOSED AND RECURRENT IDHWT-GLIOBLASTOMA (GBM) PATIENTS: A LARGE MONO INSTITUTIONAL EXPERIENCE

Abstract BACKGROUNDNGS panels allow the identification of alterations within hundreds of cancer-related genes and can guide a personalized strategy in glioma treatment. METHODS From Nov 2019 to Jan 2022 at Veneto Institute of Oncology, Padua, Italy, a large cohort of IDHwt-GBM tissues was analyzed by NGS (FoundationOne®CDx). We identified all potential actionable molecular alterations at diagnosis and/or at recurrence. High tumor mutational burden (TMB) was defined as ≥10 mutations/megabase. RESULTS We analyzed 429 IDHwt-GBM samples: NGS profile was available for 419 samples (97.7%); sample failures in 10 cases (2.3%). 351 (84%) and 68 (16%) GBM samples derived from surgery at diagnosis and recurrence, respectively. All patients received radiotherapy and/or temozolomide as first line therapy. Among all the analyzed samples, the most frequent actionable molecular alterations were: CDKN2A (57%), CDKN2B (53%), EGFR amplification (39%), EGFR mutation (24%), PTEN loss (27%), RB1 (23%), NF1 (18%), PIK3CA (18%), CDK4 (15%), MDM2 (10%), PDGFRA (8%), BRCA1-2 (7%), FGFR1-3 (7%), Myc (6%), JAK (6%), ROS1 (5%), METmut (2%), METampl (2%), BRAF V600E (2%). No NTRK1/2/3 druggable alterations were observed. High TMB was found in 18 samples. The incidence of alteration of EGFR (ampl/mut), RB1, PIK3CA was statistically different between the two subgroups of newly diagnosed and recurrent GBM samples (Fisher test). To date, 10% of patients received a personalized treatment as compassionate use, off-label use or in clinical trials (9 Dabrafenib/Trametinib, 8 Alpelisib, 3 Erdafitinib, 2 Ipatasertib, 1 Alectinib, 1 Capmatinib, 1 Palbociclib, 1 Entrectinib, 1 Pamiparib). Activity analysis is still ongoing. CONCLUSIONNGS is feasible in GBM samples. Potentially, a high rate of patients could receive a personalized treatment. The activity analysis is ongoing. However, the incidence of actionable molecular alterations may differ between diagnosis and recurrent GBM samples.

Incidence of hemorrhagic cystitis following unmanipulated peripheral blood stem cell transplantation in acute Leukemia: A retrospective single-center risk factor analysis

Hemorrhagic cystitis (HC) is an important adverse event experienced after hematopoietic stem cell transplantation (HSCT). Severe HC could lead to significant morbidity, prolonged hospitalization with increased health-care costs, and may cause considerable mortality. In order to investigate the influence of different contributing factors other than BK viruria on HC occurrence in a homogenous population, we retrospectively analyzed the potential risk factors. We conducted a retrospective study among 200 patients (median age 12.4 years, IQR: 7.9-16.1) with acute leukemia who received peripheral blood allogenic HSCT after radiation-free myeloablative conditioning regimen, in pediatric cell therapy department of Research Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Tehran, Iran, between December 2014 and December 2021. Associations between risk factors and outcomes were examined by univariable and multivariable logistic regression models. A total of 46 patients (23%) had developed HC during the study period. The median onset of HC was 29 (IQR: 24-37) days post-transplant, and it persisted for a median of 33 (7-270) days. The incidence of HC in our patients was estimated to be 3 in 1000 cases (95% CI: 2-4). The results of multivariable logistic model shows that the chance of HC in T-cell acute lymphoblastic leukemia (ALL) compared to B-cell All is nearly five times more (OR=4.88; 95%CI: (1.51-15.78), P=0.008). The incidence of HC in patients who underwent HSCT from haploidentical donors was significantly higher than full matched donors (P<0.001). Undergoing transplant from a matched unrelated and haploidentical donor both augment the chance of HC in about six times more than matched related donors (OR=6.36; 95%CI: (1.58-25.49), P=0.009 and OR=5.7; 95%CI: (1.83-17.75), P=0.003, respectively). In patients who developed HC compared to non-HC group, overall survival was much worse (P<0.001). Most studies have failed to demonstrate any relationship between late-onset HC and the dose of cyclophosphamide. In our study, although the dose of cyclophosphamide was similar in HSCT from MRD and MUD, the hazard of HC incidence was significantly higher in the latter group. This could be accredited to ATG, as in patients in the MRD group who had not received any ATG, the incidence of HC was much lower than the patients who had underwent HSCT from MUD or haploidentical donor group. Patients with T-cell ALL and those who under haploidentical HSCT had the highest incidence of HC.

Toxicity management and efficacy of carboplatin desensitization therapy for recurrent epithelial ovarian carcinoma: A real-world study.

Epithelial Ovarian cancer (EOC) is the most lethal gynecologic cancer worldwide. Carboplatin (CP) is the main chemotherapeutic agent in the treatment of ovarian cancer. However, the development of a hypersensitivity reaction (HSR) in 10% to 15% of patients with EOC is an important limiting factor for the clinical use of CP. Herein, we aimed to investigate the efficacy and safety of CP-desensitization (CP-D) therapy in the treatment of recurrent patients with EOC. Forty-seven ovarian cancer cases treated with CP-desensitization at the Istanbul University Oncology Institute were retrospectively analyzed between 01.01.2017 and 01.01.2022. The decision for CP-D was based on the patients' history of HSR and/or a positive skin test. For all patients, a 6-hour 12-step rapid drug desensitization protocol with a 30-minutes premedication regimen was used. Forty-seven patients were included in this study, and the median age at diagnosis was 53 years (range; 27-80). Twenty-one (43.7%) patients had 1 or more comorbid diseases, and 12.7% had a previous history of drug allergy. On average, HSR due to carboplatin was identified after 9 (7-16) cycles, and carboplatin was administered n = 11 (range, 3-36) times to patients. The overall survival from the first desensitization procedure (0S2) was 42.2 months (range: 25.3-59.1), and the 1-, 2-, and 5-years survival rates were 92.6%, 75.6%, and 47.2%, respectively. The objective response rate (ORR) was 78.5%. Cumulatively, 496 CP-D procedures were performed, of which 478 (96.3%) were successfully completed. None of the patients included in this study developed severe (grade 3-4) HSR during CP administration (no adrenaline was used, no need for intensive care). No deaths due to CP-D were noted. CP-D is a beneficial and safe method in treating platinum-sensitive recurrent EOC patients with CP-induced HSR.

The Accuracy of MRI in the Local Staging of Endometrial Cancer: An Experience From a Tertiary Care Oncology Institute in Pakistan.

Objective Our objective is to assess the diagnostic accuracy of contrast-enhanced magnetic resonance imaging (MRI) in identifying the depth of myometrial invasion and cervical stromal involvement in endometrial carcinoma (EC) along with nodal status and its correlation with surgical and histopathological (HP) findings. Materials and methods We performed a retrospective study on female patients at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. Patients with endometrial carcinoma (CA) were searched from the electronic record system, and a total of 188 patients fulfilling the study criteria were selected. All the patients were evaluated using a 1.5T MRI and underwent a hysterectomy. The outcome of preoperative MRI was correlated withhistopathology results, keeping pathologyas the gold standard. Results A total of 188 patients were included in the study, with a mean age of 56.67 ± 12.47 years. Of the patients, 72 (38.3%)were diagnosed with stage 1a. The second common stage was1b, seen in 43 (22.9%) patients. It was found that the staging of endometrial CA on MRI and HP were significantly correlated for myometrial invasion (stage 1a and 1b), cervical stromal involvement (stage 2b), serosal and adnexal (stage 3a), vaginal(stage 3b), and nodal (stage 3c) involvement as shown by their p-values of <0.01. However, in cases of parametrial invasion (stage 3b), bladderinvolvement, and rectal involvement (stage 4), MRI showed decreased sensitivity as shown by their p-values of 0.833, 0.87, and 0.9, respectively. Conclusion Preoperative MRI can predict local disease and low-risk patients accurately, thereby helping in proper surgical planning and avoiding more extensive surgery such as lymphadenectomy in these patients.

Frequency of skeletal metastasis on 18F-fluorodeoxyglucose positron emission tomography/computed tomography with negative computed tomography at Institute of Nuclear Medicine and Oncology

Background: Skeletal metastasis (SM) with skeletal related events (SREs) occurs in up to 70% of breast cancer and more than 50% of malignant tumors. Whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) used to characterize the metabolic, anatomic, and morphologic status of suspected bone lesions. SMs are detected using multiple modalities; however, FDG PET/CT may offer a single investigation to detect SM combining the strength of functional imaging and radiological imaging simultaneously. Aims and Objectives: This study was to assess the frequency of SM on 18F-FDG PET/CT with negative CT at Institute of Nuclear Medicine and Oncology (INMOL). Materials and Methods: This cross-sectional study included a sample of total 50 patients with SM of known primary malignancies who underwent 18F-FDG PET/CT scan at INMOL Cancer Hospital, Lahore. Results: Of the 50 patients, we discovered the concordant findings between PET and CT as both PET+/CT+ in 38 patients (76%) whereas in 12 patients (24%) with PET+/CT- findings were discordant. CT was unable to detect SM in at least 12 patients. The maximum standardized uptake value (SUVmax) of SM in patients with negative CT found to be slightly higher as 5.2±4.1 (range: 2.5–7.8) than in patients with positive CT finding as 4.8±2.8 (range: 3.9–5.8) with P=0.76. P-value is insignificant this means that high SUV is not typical or conclusive evidence of metastasis. Conclusion: Despite limited data, this study has demonstrated high concordance between FDG PET and CT scan in detecting SM. Furthermore, the study has shown that 18F-FDG PET appears to have slightly better detection efficiency as compared to CT for identification of SM which is statistically insignificant. The study demonstrated that SUV is higher in PET and CT discordant cases; however, it does not provide conclusive information favoring diagnosis of SM.

Editorial introductions.

Editorial introductions.

Professors Constantin and Gheorghe Țîbîrnă: promoters of personalized surgery of thyroid cancer

For 40 years (1980-2020) in the Department of tumor of Head and Neck Surgery of the Oncological Institute of the Republic of Moldova, the Clinic University „N. Testemitanu” were treated 18549 of patients with nodular pathology of the thyroid gland – which 6183 treated with cancer. It should be noted that 12366 were precancerous conditions: adenomas – 7296 (59%), toxic nodular goiter 2226 (18%), autoimmune thyroiditis (Hashimoto) – 2844 (23%), 1078 werechildren, 105 (9.7 %) with cancer.The incidence of thyroid cancer increased for about 4 times, in 1980 – 70 of patients (1.7%ooo), in 2020 – 294 of patients (8.3%ooo). The incidence of mortality was stabilized: 1980 -0.4%ooo), 2020 – 0.6%ooo). The incidence of prevalence was increased by 17 times, 1980 – 6.4%ooo), 2020 – 120.5%ooo).Depending on the sex, thyroid cancer was on average in women – 87%, in men 13%, the ratio being 9:1. How to explain the higher incidence of thyroid disease in women:In the hormonal activity in women, there are considerable physiological fluctuations during the life (puberty, menstrual cycle, pregnancy, births, abortions, climacteric involution, etc.). As a result, of hormonal disordes lead to some thyroid pathology, which is one of the most labile hormonal glands.Molfologically we mention that the first is papillary cancer (55.5%), in second – folliculary (32.8%), third – medullary cancer (7.8%), last one – undifferentiated (3.9%).Three types of surgery have been developed in the treatment of thyroid cancer: typical surgery, extended and combined surgery.Professors Constantin and Gheorghe Țîbîrnă from the typical operation are elaborated and implemented the operation–maximal subtotal resection of the thyroid gland with transplantation of the parathyroid glands with the vascular bundle in the sterno-cleido-mastoid muscle.From atypical operation, together with professor Nicolae Gladun, he is developed a surgery. Combined thyrodectomy with sternotomy, and paratracheal, mediastinal, anterior and posterior lymph nodes removed (T4b).

Impact of the COVID-19 Pandemic on Cancer Staging: An Analysis of Patients With Breast Cancer From a Community Practice in Brazil.

A nationwide lockdown was enforced in Brazil starting in March 2020 because of the COVID-19 pandemic when cancer screening activities were reduced. In this study, we evaluated the impact of the COVID-19 pandemic on breast cancer (BC) diagnosis. We extracted data from the medical records of patients age older than 18 years who were diagnosed with BC and started treatment or follow-up in private oncology institutions in Brazil between 2018 and 2021. The primary objective was to compare the stage distribution during the COVID-19 pandemic (2020-2021) with a historical prepandemic control cohort (2018-2019). Early BC was defined as stage I-II and advanced disease as stage IV. We collected data for 11,753 patients with an initial diagnosis of BC, with 6,493 patients in the pandemic (2020-2021) and 5,260 patients in the prepandemic period (2018-2019). We observed a lower prevalence of early-stage BC (63.6% v 68.4%) and a higher prevalence of advanced-stage BC (16.9 v 12.7%), after the onset of the pandemic (both P < .01). This pattern was similar for both estrogen receptor-positive/human epidermal growth factor receptor 2-negative and human epidermal growth factor receptor 2-positive tumors: significantly decreased in the early stage from 69% to 67% and 68% to 58%, respectively, and a considerable increase in advanced-stage disease from 13% to 15% and 13% to 20%, respectively. For triple-negative BC, there was a significantly higher percentage of patients with advanced-stage disease during the pandemic (17% v 11%). Overall, age 50 years or older and postmenopausal status were associated with a greater risk of advanced stage at diagnosis during the pandemic period. We observed a substantial increase in the number of cases of advanced-stage BC in Brazil during the COVID-19 pandemic.

The role of the Academician of ASMDM C. Țîbîrnă in the development of oncological surgery in various locations (head/neck, thoracoabdominal, liver surgery, etc.)

The idea of the state scientific program comes under the name „Modern personalized surgery in the diagnosis and complex treatment of tumors in children”. On March 24-25, 2022, at the Academy of Sciences of Moldova, the National Scientific Conference with International Participation „Modern Personalized Surgery for Adults and Children. Surgery of the future”, dedicated to the Honorary Member of the ASM, university professor, illustrious surgeon Constantin Țîbîrnă, founder of the local surgery. C. Țîbîrnă, being a polyvalent surgeon, during his activity developed local oncological surgery in various locations (head-neck, thorocoabdominal, liver surgery, etc.). The following were analyzed: indices of mortality incidence and cancer prevalence in the Republic of Moldova during the years 1980-2020.Thus, during this period there was a clear increase in morbidity rates due to malignant tumors in the Republic of Moldova. In 1980, about 5860 of primary patients (149.0 per 10 0000 population) were registered. Over 30 years, in 2020 the number of patients will increase to 9391 (264.4 per 100,000 habitants). Mortality during this period had a stable increase. In 1980, 3515 patients died for malignant tumors (95.0 per 100,000 population), in 2020 mortality rates increased to 4867(136.9 per 100,000 population).Regarding the prevalence indices, it should be mentioned that in 1980, 26,715 of patients (668.3% 000) were registered in the Cancer Registry of the Republic of Moldova. In 2020, the prevalence indices was doubled - 50,980 (1433.9‰000). This index demonstrates to us the efficiency of the oncological assistance of the Oncological Institute team in the treatment of cancer in the Republic of Moldova.The existence of the European Society of Oncological Surgery (ESSO) as well as the World Federation of Surgical Oncology Societies (WFSOS) confirms the recognition of the specialty of oncological surgery.About 7,700 patients are treated annually for surgery. In the oncology clinic more than 65% perform typical operations. Wide and combined surgeries prevail in university clinics (360 patients). In his activity, the famous surgeon C. ȚÎbîrnă perfected the oncological surgery in the torocoabdominal region, at the Republican Clinical Hospital (prof. N. Gladun, acad. V. Hotineanu and prof. A. Hotineanu). In the Oncology Clinic he developed new methods of surgical treatment of local tumors spread in the head and neck region (acad. Gh. Ţîbîrnă and associate professor A. Țîbîrnă). As a result he proposed:To include in the current nomenclature of the Ministry of Health - „Overspecialization in cancer surgery”, which will create the legal framework for the operation of this specialty.To organize the Oncological Surgery Society of the Republic of Moldova and the oncological surgery department within USMF „N. Testemitanu”.

Features of lymph node metastasis depending on intratumoral heterogeneity of non-small cell lung cancer in patients with different morphological changes in the bronchial epithelium

The aim of the study: to examine the relationship between the morphological diversity of non-small cell lung cancer and the frequency of lymph node metastasis in groups of patients with different epithelial conditions in the bronchi adjacent to the tumor. Material and methods. Surgical specimens from 90 patients with non-small cell lung cancer, who were treated in the Thoracoabdominal Department Of The Research Institute Of Oncology Of The Tomsk National Research Medical Center in the period from 2009 to 2017 were studied. The histological type of cancer was determined according to the who classification (2020). Lepidic, acinar, papillary, micropapillary, solid and solitary tumor cells were isolated in the parenchymal component of adenocarcinoma. In the parenchymal component of squamous cell carcinoma, 5 types of structures were distinguished: with keratinization, consisting of atypical cells of the prickly type without keratinization, consisting of atypical cells of the basaloid type, built of atypical cells with pronounced polymorphism, single tumor cells. Results. In patients with isolated basal cell hyperplasia, acinar (37 %), papillary (29 %) and solid (27 %) patterns were found less frequently in cases with metastatic regional lymph nodes compared to those without metastatic lymph nodes (63 %; p=0.05; 71 %; p=0.05; 73 %; p=0.01, respectively). In patients with isolated basal cell hyperplasia of the bronchial epithelium, in cases with the presence of lymph node metastasis in the parenchymal component of squamous cell carcinoma, structures 1 (with keratinization) (17 %), 2 (spiky pattern) (33 %) and 4 (polymorphic pattern) (29 %) were less frequently detected compared to those without metastases in regional lymph nodes (83 %; p=0.01; 67 %; p=0.02 and 71 %; p=0.01, respectively). In patients with a combination of basal cell hyperplasia and squamous metaplasia, a spiny pattern (65 %), a basaloid pattern (100 %), a polymorphic pattern (82 %) and single tumor cells (89 %) were more frequently detected in cases with metastatic lymph nodes than in cases without metastatic lymph nodes (35 %; р=0.04; 0 %; р=0.01; 18 %; р=0.01; 11 %; р=0.01, respectively). Conclusion. The data obtained clarify the available information on the significance of the morphological heterogeneity of the tumor for predicting the course of adenocarcinoma and squamous cell carcinoma of the lung.

Results of Two-Years Mammographic Screening in the Kaluga Region

Objective: approbation of the project of mass breast cancer mammographic screening in the Kaluga Region.Material and methods. From April 2018 to December 2019, screening mammography was performed in 35,439 women aged from 38 to 93 years (mean age 57.33 ± 8.07 years). The study was carried out on mobile mammography complexes assembled on Russian KamAZ vehicles with Russian-made equipment from Amiko company. Mammography was performed in frontal and oblique projections. BI-RADS ACR international classification was used to standardize the identified changes and assess the sensitivity and specificity of the study method.Results. Out of the total number of women examined, pathological changes (BI-RADS IV–V) were assumed according to mammography data in 778 (2.2%) cases, of which 700 (1.98%) patients appealed to an oncological institution. Benign processes were found in 394 (1.11%) patients, breast cancer in 164 (0.46%). Without verification of the diagnosis, 137 (0.39%) patients remained under the supervision of oncologists. Distribution of detected tumors by stages for 2 years of observation: stage 0 – 7, stage 1 – 73, stage 2 – 56, stage 3 – 13, stage 4 – 3. The stage was not set in 4 cases. The total number of those examined with verification of the diagnosis in the oncological institution was 596. The proportion of correct diagnoses was 94%. The total number of diagnostic errors that would occur in the absence of a true double scan accounted for 36 (6%) cases.Conclusion. The proposed screening method makes it possible to increase the breast cancer detection in the early preclinical stages of the disease, to provide the available diagnostics for the population due to mobile mammography complexes, and to speed up the process of diagnostics and further hospitalization for examination and necessary treatment according to the disease stage in a specialized oncological institution.

Extended adjuvant endocrine treatment for premenopausal women: A Delphi approach to guide clinical practice.

The use of an aromatase inhibitor (AI) in combination with ovarian function suppression (OFS) has become the mainstay of adjuvant endocrine therapy in high-risk premenopausal patients with hormone receptor-positive breast cancer. Although five years of such therapy effectively reduces recurrence rates, a substantial risk of late recurrence remains in this setting. Multiple trials have shown that extending AI treatment beyond five years could offer further protection. However, as these studies comprised only postmenopausal patients, no direct evidence currently exists to inform about the potential benefits and/or side effects of extended AI + OFS therapies in premenopausal women. Given these grey areas, we conducted a Delphi survey to report on the opinion of experts in breast cancer treatment and summarize a consensus on the discussed topics. A total of 44 items were identified, all centred around two main themes: 1) defining reliable prognostic factors to pinpoint premenopausal patients eligible for endocrine therapy extension; 2) designing how such therapy should optimally be administered in terms of treatment combinations and duration based on patients' menopausal status. Each item was separately discussed and anonymously voted by 12 experts representing oncological institutes spread across Italy. The consensus threshold was reached in 36 out of 44 items (82%). Herein, we discuss the levels of agreement/disagreement achieved by each item in relation to the current body of literature. In the absence of randomized trials to guide the tailoring of extended AI treatment in premenopausal women, conclusions from our study provide a framework to assist routine clinical practice.

Moroccan Medicinal Plants Used to Treat Cancer: Ethnomedicinal Study and Insights into Pharmacological Evidence.

Cancer is one of the major medical challenges, with an unacceptably high death toll worldwide. In Morocco, medicinal plants continue to play a pivotal therapeutic role despite the development of modern sanitation systems. In the current study, an ethnobotanical survey was carried out at the Moroccan national institute of oncology, Rabat, and we aimed at (1) establishing an exhaustive inventory of indigenous knowledge of Moroccan medicinal plants used to manage cancer and (2) confirming the reported ethnopharmacological uses through bibliometric review. An ethnobotanical survey was conducted with 291 cancer patients at the Moroccan National Institute of Oncology, Rabat, during a period of 4 months, from February to May 2019, through semistructured interviews. Ethnobotanical indices, including informant consensus factor (FIC), use report (UR), relative frequency citation (RFC), botanical family use value (FUV), fidelity level (FL), and index of agreement on remedies (IAR), were employed in data analyses. The survey revealed that 39 medicinal plants belonging to 27 botanical families and 38 genera were used to treat cancer. The most used ethnospecies were Aristolochia longa with the highest RFC value (0.096), followed by Nigella sativa, Ephedra alata, Euphorbia resinifera, and Lavandula dentata, éwith RFC values of 0.072, 0.054, 0.044, and 0.044, respectively. In regard to the plant families, Lamiaceae contributed the highest number of plants with five species (FUV = 0.034), followed by Asteraceae (4 species; FUV = 0.020), and Fabaceae (4 species; FUV = 0.020). The leaves are the most popular plant part used by the studied population against cancer; otherwise, decoction was the most commonly used method for remedy preparation and the highest FIC was noticed for uterine cancer treatment (0.86). Considering these findings, further investigations into the recorded plant species should be performed to assess phytochemical constituents and pharmaceutical benefits in order to identify their active compounds for any drug formulations.

Safety of mRNA-COVID-19 Vaccines in Patients With Thoracic Cancers

BackgroundPivotal trials of COVID-19 vaccines did not include cancer patients with questions remaining in this population. Particularly in patients with thoracic malignancies receiving anticancer treatments, the safety of these vaccines has so far been little investigated.MethodsThis is a prospective trial of patients with thoracic cancer receiving anticancer treatments and COVID-19 vaccines at the Division of Thoracic Oncology of European Institute of Oncology between February and September 2021.Results207 patients affected by thoracic cancers (199 lung cancers and 8 mesotheliomas) had received Covid-19 vaccines (206 mRNA vaccines and 1 virus-vectored vaccine). The majority of patients had at least one comorbidity (76.3%). They were concomitantly treating with targeted therapy (TT) (45.9%), immunotherapy (IO) (22.7%), and chemotherapy (CT) (14%). A total of 64 AEs (15.6%) were observed after administration of Sars-Cov-2 vaccine. The majority of AEs were grade 1 [G1] (6.3%) and G2 (8.8%), only two events were G3 (0.5%). The median follow-up was 9 months (range 1-22 months), during this follow-up 21 patients (10.1%) had a positive nasal swab, most of the patients were asymptomatic (67%) and the symptomatic ones (33%) had mild symptoms and fewer complications and hospitalizations.ConclusionsCOVID-19 m-RNA vaccines appear to be safe in the cohort of patients with thoracic malignances in active treatment, including those receiving immunotherapy. Considering the high morbidity and mortality associated with COVID-19 in patients with lung cancer receiving active treatments, our study supports the current vaccine prioritization, third and/or fourth dose, of all cancer patients with active treatment.Micro-abstractThis is a prospective trial of 207 patients with thoracic cancer receiving anticancer treatments and COVID-19 vaccines.After long follow-up, there were no safety signals of concern and only 0.5% of patients experienced grade 3 vaccine-related adverse events.Our study supports the current vaccine prioritization, third and/or fourth dose of all lung cancer patients with active treatment.

The Role of miR-375-3p, miR-210-3p and Let-7e-5p in the Pathological Response of Breast Cancer Patients to Neoadjuvant Therapy.

Background and Objectives: Prediction of response to therapy remains a continuing challenge in treating breast cancer, especially for identifying molecular tissue markers that best characterize resistant tumours. Microribonucleic acids (miRNA), known as master modulators of tumour phenotype, could be helpful candidates for predicting drug resistance. We aimed to assess the association of miR-375-3p, miR-210-3p and let-7e-5p in breast cancer tissues with pathological response to neoadjuvant therapy (NAT) and clinicopathological data. Material and methods: Sixty female patients diagnosed with invasive breast cancer at The Oncology Institute “Ion Chiricuță”, Cluj-Napoca, Romania (IOCN) were included in this study. Before patients received any treatment, fresh breast tissue biopsies were collected through core biopsy under echographic guidance and processed for total RNA extraction and miRNA quantification. The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) database was used as an independent external validation cohort. Results: miR-375-3p expression was associated with more differentiated tumours, hormone receptor presence and lymphatic invasion. According to the Miller–Payne system, a higher miR-375-3p expression was calculated for patients that presented with intermediate versus (vs.) no pathological response. Higher miR-210-3p expression was associated with an improved response to NAT in both Miller–Payne and RCB evaluation systems. Several druggable mRNA targets were correlated with miR-375-3p and miR-210-3p expression, with upstream analysis using the IPA knowledge base revealing a list of possible chemical and biological targeting drugs. Regarding let-7e-5p, no significant association was noticed with any of the analysed clinicopathological data. Conclusions: Our results suggest that tumours with higher levels of miR-375-3p are more sensitive to neoadjuvant therapy compared to resistant tumours and that higher miR-210-3p expression in responsive tumours could indicate an excellent pathological response.