The crucial role of the tumor board in the diversity of prostate cancer cases

Sorin Bulgariu 

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania 

Personalized medicine is the adaptation of the treatment to the specifics of the patient. Patients with the same clinical diagnosis may respond differently to the same treatment. For some patients, the treatment may be effective, while in others, side effects may occur, or the desired clinical benefit may not be obtained. This is due, in many cases, to genetic differences between patients. The treatments tailored to different categories of patients have medical as well as economic benefits and, consequently, are important not only for doctors and patients, but also for health authorities and insurance companies. The early selection of patients most likely to respond to a new treatment increases the success rate in the development of new therapies and decreases the costs of applying the new treatments. Prostate cancer is the second most common in men, as well as the second leading cause of cancer death in men. Generally, one in nine men will be diagnosed with prostate cancer in their lifetime. We have to keep in mind the detail that the prostate cancer emerges at younger ages, as well as its aggression and greater extension even at these ages. When limited to the prostate, the chance of a successful treatment is very high. However, there is no cure for metastatic prostate cancer. The present study intends to address the optimal attitude towards the difficult clinical case of a relatively young, asymptomatic patient with biological signs of an advanced form, detected at a routine examination and confirmed by subsequent investigations, as well as obtaining the ideal advice of the tumor board.


Do the limitations of the guidelines mean professional freedom?

Ion Christian Chiricuţă 

AMETHYST Radiotherapy Center, Otopeni, Romania 

 The main goal of the tumor boards is to indicate the most recommended therapy for each individual case. The indication of a treatment sequence is one thing, but the possibility to follow it is another and completely different thing. From the actual data, 40-60% of the patients are not treated according to the guidelines’ indications and 30-40% of the patients receive a treatment not based on clinical evidence. A quite large number of patients receive a treatment that harms their health. To follow the treatment recommended by the guideline does not guaranty a successful result. It does not exist in the actual guidelines a personalized recommendation for each patient and we must not forget the importance of guidelines in the clinical judgement. These guidelines should never substitute the clinical judgment. The clinical judgment should always be used when applying a guideline to a patient, because it is impossible to develop guidelines that apply to all situations. What should be better for the patient in case: to recommend a treatment that could not be followed easy, or to recommend a treatment that should help him in that specific situation? Should a not followed guideline indication be considered as malpractice? We will present, from our clinical experience, some patients in which the guideline recommendations did not fit for their special case. The treatment applied is responsible for the survival and quality of life of these patients. 

Software-aided approach to protein structure

Iolanda Dumitrescu 

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania

Objective. Proteins are doing the most important biological and chemical functions in a cell. The biological functionality of proteins depends mainly on their spatial structure. Determining the three-dimensional shape of a protein is pivotal in indicating its function. Materials and method. Once the structure of a particular protein is solved by experimentation, the coordinates representing the spatial position of each atom of the structure are issued. Specialized software might produce the spatial view of the protein. To observe and compare protein structures a straight forward. To compare protein structures is to analyze two or more protein structures for similarity. Intermolecular, intramolecular and hybrid distance approaches have to be mentioned. Protein structures comparison allows further the classification of the structure data and the identification of relationships among structures. Results. Tools for the development of protein structure analysis must be issued as computer-aided approaches, algorithms and methods. For protein structure visualization, we analyzed software programs for molecular graphics: stand-alone and web-based. The comparative analysis of proteins involves the direct alignment and superposition of structures in space to reveal which part of structure is conserved and which part is different. Some structure comparison web servers have been documented. A protein structure classification system must provide a comprehensive and evolutionary view of known structures and to classify newly obtained proteins. Two main classification systems have been reviewed. Conclusions. Protein structural bioinformatics is an essential part of bioinformatics. In the context of precision medicine, the interpretation of analysis outcomes must be done by a multidisciplinary team, including physicians, geneticists, bioinformaticians, statisticians and biologists, which must transform the information in the primary data into knowledge.

Primary mucosal melanoma of the vagina. A case report and literature review

Ana-Maria Ilie1, Nicolae Popescu2, Mihaela Dumitru1, Laura Rebegea1,3, Mihaela Vlad4

1. Radiotherapy Department, “Sf. Ap. Andrei” Emergency Clinical Hospital, Galaţi, Romania
2. Obstetrical-Gynecological Clinic, “Sf. Ap. Andrei” Emergency Clinical Hospital, Galaţi, Romania
3. Medical-Clinical Department, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University of Galaţi, Romania
4. Oncology Department, “Sf. Ap. Andrei” Emergency Hospital, Galaţi, România

Objective. Malignant melanoma (MM) of the vagina is an extremely rare variant of melanomas, an aggressive type of cancer with poor prognosis. Although it was first reported in 1887, there have been no more than 500 primary vaginal melanoma cases reported in modern literature. MM of the vagina always presents as deeply invasive tumors, and the five-year overall survival varies between 5% and 25%. We present a review about this type of cancer, because a few cases are reported in the literature. Materials and method. We present the case study of a 70-year-old female who presented with a vaginal tumor; the initial pathological diagnosis was epidermoid carcinoma and was confirmed by immunocytochemistry as primary malignant melanoma of the vagina. The initial workup was performed and there were identified distant pulmonary metastases. Results. We present this rare case and the treatment challenges. The patient was treated with immunotherapy with checkpoint inhibitors, the standard treatment in cutaneous metastatic malignant melanoma. We also discuss the role of palliative radiotherapy in the multidisciplinary management. The introduction of immunotherapy and the targeted therapy in advanced and metastatic MM led to a good local control and overall survival. Conclusions. Mucosal melanoma differs significantly from cutaneous melanoma regarding presentation, genetic profile, staging, response to treatment, pattern of progression, and the treatment should be tailored to each individual.

Oncological treatment of ovarian neoplasm in the context of hemodialysis

Cătălina Lăcustoiu, Oana Popescu, Irina Anghel, Ştefania Marinescu, Mădălina Tolea, Anca Pîslariu, Ismail Gener, Cornelia Niţipir

“Elias” University Emergency Hospital, Bucharest, Romania

Objective. Optimizing cytotoxic drug handling in terms of dosage adjustment and time of administration regarding the dialysis sessions. Materials and method. We present the case of a patient with locally advanced epithelial ovarian cancer, with acute renal failure, requiring hemodialysis. Results. A 56-year-old patient had elevated ROMA (Ovarian Malignancy Risk Algorithm) score and locally advanced bilateral ovarian carcinoma, with abdominopelvic peritoneal carcinomatosis with proposed imaging staging T3c N0 M0. The intraoperative biopsy confirmed ovarian serous carcinoma FIGO (International Federation of Gynecology and Obstetrics) stage IIIC and peritoneal carcinomatosis. After complete tumor cytoreduction surgery, intraperitoneal hyperthermic chemotherapy was performed with cisplatin 100 mg for 60 minutes at 41 degrees Celsius, using the Coliseum technique. The patient developed acute renal failure, as a reaction to cisplatin administration, with hemodialysis requirement (stage III KDIGO – Kidney Disease Improving Global Outcomes). Our team decided to administer paclitaxel 175 mg/m2 and carboplatin in reduced doses, followed by hemodialysis 24 hours after the administration of carboplatin for a period of 4 hours, according to international studies and guidelines. Paclitaxel is metabolized mainly in the liver, with a little influence of hemodialysis on its pharmacokinetics. The carbo­platin dose was calculated by the Calvert formula, considering that the eGFR (estimated glomerular filtration rate) was 0 ml/min. The patient is currently undergoing hemodialysis twice a week and with diuresis of approximately 1.5 L/day. The nephrology team recommended diuretics on the day of treatment and dapagliflozin, which is a sodium-glucose inhibitor with a good nephroprotective effect on the proximal renal tube, the main site of nephrotoxicity for carboplatin. Conclusions. The combination of paclitaxel and carboplatin can be administered to an advanced-stage epithelial ovarian cancer patient with advanced nitrogen retention. To ensure a favorable therapeutic effect with limited side effects, the hemodialysis should be initiated 24 hours after the administration of carboplatin.

Strategies and tools for an effective patient-clinician communication: the case of oncology patients

Octavia-Luciana Madge

University of Bucharest; 1st Clinic of General and Oncological Surgery, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania

Introduction. Patient-physician communication is a fundamental skill for clinical practice. In recent years, there has been an increasing emphasis on patient autonomy, patient-centered care, the informed patient, and the importance of effective patient-physician communication is increasing in this context. An effective communication with the doctor has a therapeutic effect on the patient, especially in the case of oncology patients. Objectives. The aim of this study is to explore the essential elements of effective patient-clinician communication and to highlight important elements in the communication with oncology patients. Methodology. Strategies and tools currently used in the interaction between doctor and patient are analyzed, starting from recent researches. Results. Different strategies for communicating with patients have been used in the medical practice and a series of tools and protocols have been developed in order to improve the interaction between patient and clinician, and in the end, the quality of care. Recent studies have highlighted the potential of these tools in supporting both patients to overcome conditions which they experience during the disease and clinicians to overcome the different challenges of communicating with patients in different contexts. Conclusions. The communication skills are essential for doctors in all specialties in their interaction with patients, but doctors should be trained in the field of communication techniques. 

Treating renal cell carcinoma in a young adult: challenges and approaches. Case report

Elena Adriana Mateianu1, Adelina Silvana Dragomir1,2, Andreea Mihaela Radu3, Isabela Anda Komporaly1,2, Claudia Paraschiva Seliuc1, Maria Alexandra Baiulescu2, Raluca Ioana Mihăilă1,2, Lidia Anca Kajanto1,2, Dana Lucia Stănculeanu1,2 

1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania
2. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
3. AMETHYST Radiotherapy Center, Bucharest, Romania

Objective. We present the case of a challenging me­ta­static renal cell carcinoma (RCC) in a young adult, with less common histological pattern and three lines of treatment (targeted therapy and immunotherapy). Case pre­sen­tation. A 31-year-old patient presented to the on­co­logy department in January 2018 with the diagno­sis of RCC with clear cells and predominant papillary features, for which he underwent radical nephrectomy (2014) and surgical resection of a retroperitoneal recurrence (2017). The follow-up computed tomography (CT) scans revealed pulmonary, hepatic and retroperitoneal metastases. The patient met the criteria for the low-risk group, according to MSKCC Prognostic Model, and began sunitinib treatment, with positive evolution, requiring dose escalation. After two years of progression-free survival (PFS), his performance status (PS) started to decline and the CT scan revealed disease progression. The treatment was changed to nivolumab, which caused an initial pseudoprogression of the metastases. Immunotherapy was not well tolerated, as he developed serious immune-related adverse events (hypophysitis) and his PS deteriorated furthermore. Secondary PFS was only 6 months, as CT confirmed progressive disease (iRECIST criteria): increase of the known neoplastic lesions, as well as new metastases. Therefore, third-line therapy with cabozantinib was initiated since November 2020. The patient had a favorable evolution, with an augmentation of PS and of the quality of life. Despite mild gastrointestinal adverse effects, which led to dose reduction, cabozantinib was well tolerated. Conclusions. RCC is a possible diagnosis even in younger patients and may represent a challenging disease due to its resistance to various tyrosine-kinase inhibitors and immune checkpoint inhibitors. The histopathological feature of papillary morphology has also a negative impact on prognosis and can be taken into consideration while choosing therapy sequencing.

Multidisciplinary approach – Merkel cell carcinoma in a young patient. Clinical case and review

Raluca Mihăilă1, Liliana-Cristina Popescu1, Elena Mateianu1, Isabela Komporaly1, Adelina Silvana Dragomir1, Claudia Seliuc1, Bogdan Georgescu1, Lidia Kajanto1, Dragoş Mitulescu3, Dana Lucia Stănculeanu1,2 

1. Department of Medical Oncology I, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania
2. Department of Oncology, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
3. Departament of Radiotherapy II, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania

Objective. Merkel cell carcinoma (MCC) is a rare form of cutaneous cancer, the five-year survival rate for metastatic disease being 25% (risk factors: UV radiation, the infection with Merkel cell polyomavirus [MCPyV], chronic immunosuppression). The multimodal treatment for MCC includes surgery, chemotherapy, radiotherapy and immunotherapeutic treatments. We present the case of a 21-year-old patient diagnosed with metastatic MCC and treated in our department. Materials and method. The patient was diagnosed in 2018 with unknown primary Merkel cell carcinoma. The patient was referred to a plastic surgery department for an enlarged left inguinal adenopathy and excisional lymph node biopsy was recommended. The histopathological and immunohistochemistry and imaging scans reports confirmed a stage IV (pTxNxM1) unknown primary Merkel cell carcinoma with lymph node meta­stases. The multimodal treatment included postoperative local radiotherapy and immunotherapy as the first-line treatment option. The patient started the treatment with avelumab, relatively well tolerated, with mild iatrogenic hyperthyroidism and hypothyroidism. The follow-up during treatment indicated partial regression at first evaluation and the PET-CT examination from April 2019 showed no signs of metabolically active lesions. The treatment was discontinued due to personal problems and, unfortunately, at the next follow-up, new lymph node metastases in the left axillary region were detected at the PET-CT, confirmed by biopsy. The treatment with avelumab was resumed, with complete response. Results. Although the patient has poor prognosis factors (young age, lymph node metastasis with no primary tumor), fortunately he maintained the remission, similar to data from literature. Regarding the adverse events, the patient presented reversible iatrogenic hyperthyroidism and hypothyroidism. Conclusions. Regarding the particularities of this case report, we can emphasize the young age of the patient at diagnosis, the rare form of skin cancer – Merkel cell carcinoma, the lymph node metastasis with no primary tumor, the limited treatment options and a favorable treatment response, with good quality of life and reversible adverse events. 

Bone tumors – a multidisciplinary challenge

Raluca Mihăilă1, Liliana-Cristina Popescu1, Elena Mateianu1, Isabela Komporaly1, Adelina Silvana Dragomir1, Beatrice Anghel3, Mihai Georgescu1, Bogdan Georgescu1, Sorin Bogdan3, Dana Lucia Stănculeanu1,2

1. Department of Medical Oncology I, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania
2. Department of Oncology, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
3. Sanador Oncology Center, Bucharest, Romania

Objective. Primary malignant bone tumors are rare and heterogeneous, and the diagnosis and multimodal treatment require a multidisciplinary approach in specialized centers, involving pathologists, radiologists, surgeons, and radiation and medical oncologists. The early referral to a specialist center that provides a multidisciplinary diagnosis and therapeutic approach and manages a high number of cases annually could improve the survival for these young patients. Materials and method. The multidisciplinary management of osteosarcoma, chordoma and Ewing’s sarcoma includes surgery, radiotherapy and systemic treatment, which are reviewed in this case series presentation. Surgical excision is the primary treatment for localized bone tumor. Radiation therapy is usually necessary, but chemotherapy plays an important role in some chemosensitive subtypes (high-grade osteosarcoma). In other subtypes, considered chemoresistant (such as chordoma), new targeted therapies have showed improvement in the disease management. Results. The cases presented included chordoma, osteosarcoma and Ewing’s sarcoma patients from our clinical department. The first case is a 58-year-old male patient, with multiple comorbidities, diagnosed with sacrococcygeal chondroid chordoma in 2019. Our patient’s tumor was inoperable and local recurrence was observed after radiotherapy. Targeted therapy was an option and the patient started imatinib 800 mg/day, with clinical and imagistic response. The second case is a 37-year-old female patient diagnosed with right knee high-grade osteosarcoma. The imagistic work-up (MRI, PET-CT) confirmed the local disease. The patient started MAP-EURAMOS protocol, with reversible hepatic severe toxicity, but with clinical benefit (remission of pain syndrome, without functional impotence – impact on quality of life). Surgery was indicated due to good response to neoadjuvant treatment. The third case is a 27-year-old patient diagnosed with spine Ewing’s sarcoma in 2009, amendable to surgery with adjuvant chemotherapy and radiotherapy. In 2020, pleural and pulmonary progression was diagnosed, associated with pain syndrome by the invasion of the costal grid. Chemotherapy was started – Ewing VDC/IE protocol, well tolerated, with hematological grade I/II toxicity, with complete response and indication for bone marrow transplant. Conclusions. Given the diagnosis at a young age, the unfavorable prognosis, the effects and the adverse events of multimodal treatments in the short and long run, the diagnosis, treatment and follow-up of these patients should be performed in specialized reference centers, with case studies and access to clinical trials.

A case report of breast cancer with bone and gastric metastases

Ştefania Loredana Negoianu, Elisabeta Mădălina Drăgănescu, Laura-Teodora Apostol-Pini, Sabina Maria Petru

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania

Breast cancer is the most common type of cancer in women, accounting for 20-32% of all cancers. Every year, 1.7 million new cases of breast cancer are diagnosed and more than 520,000 women die from it. We present the case of a 54-year-old woman with no significant pathological history, diagnosed in January 2017 with hypercalcemia, severe anemia, left breast tumor (biopsy – lobular carcinoma, hormone-positive, HER2-negative) and multiple bone metastases (bone scintigraphy). She received chemotherapy with epirubicin + cyclophosphamide + zoledronic acid (February-June 2017), followed by hormonal therapy and zoledronic acid monthly (July 2017 – February 2019). She also received palliative external radiotherapy (lumbosacral vertebrae – August 2017). In March 2019, the patient complained of epigastric pain and early satiety. Upper digestive endoscopy and biopsy were performed, and the pathological and immunohistochemistry exams revealed: infiltrative tumor of lobular breast carcinoma in the gastric mucosa, hormone-positive, HER2-negative. Chemotherapy with docetaxel was initiated (April 2019 until present). In May 2019, the patient received radiotherapy for left clavicle metastasis. In July 2020, the patient was diagnosed with COVID-19, with minimal symptoms. In April 2021, the CT scan revealed: dimensional progression of the right neck and femoral head metastases (palliative irradiation was performed – May 2021); a mixed (solid-liquid) cystic lesion of pericardium with effusion or effusion level – probably, blood (with aspect of pericardial metastasis). Cardiac ultrasound was performed: echogenic, inhomogeneous area, anterior to the right ventricle; it did not appear to be related to the pericardium. Cardiac metastases are not as rare as considered, their incidence ranging from 2.3% to 18.3%, most commonly from lung cancer. The case was presented to the Multidisciplinary Oncological Commission of the “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, and the conclusion was: CT monitoring every 3 months.

Histopathological working protocol in the multidisciplinary approach of surgical pathology of the mammary gland after chemotherapy

Ştefania Ariana Neicu1, Adina Elena Ene1, Mădălina Gabriela Radu1, Roxana Maria Pridie1, Cristina Amalia Guti1, Constanţa Ioniţă1, Flavia Ultimescu1, Mihai Ceauşu1,2

1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania
2. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

Objective. Breast cancer today must be managed by a multidisciplinary team, including surgeon, pathologist, radiologist, oncologist and radiotherapist. Post-chemotherapy breast is a challenge for the pathologist due to the new complex work and reporting protocols. The pathology report plays a key role for the therapeutic decision and needs standardization, in order to facilitate the work of the oncologist, as well as the research in breast cancer field. Complete clinical and imaging data are of critical importance for the elaboration of a correct pathological report. Materials and method. We set out to present the current macroscopy and micro­scopy protocol of the Pathology Department of the “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, in order to emphasize the stages in which the pathologist needs the contribution of the other team members of the tumor board. The working protocol is detailed for the different types of samples received: mastectomy specimens, lumpectomy, sentinel lymph nodes and axillary lymph node dissection. Results. We identified the main concerns of the pathologist related to post-chemotherapy breast samples: problems of sample orientation, difficulties in identifying multicentric tumors, or the tumor bed in case of a pathologic complete response, and we emphasized the importance of good interdisciplinary collaboration within the tumor board. Conclusions. The pathologist integrates the clinical and imaging data with the pathological aspects in order to elaborate a complete diagnosis. The collaboration of all members of the multidisciplinary team streamlines the work of the pathologist and prevents errors. Current, standardized work protocols require additional time and effort from both the pathologist and all members of the multidisciplinary team. The interdisciplinary collaboration helps to improve the quality of the pathologist’s work and is beneficial for breast cancer patients.

Prognostic factors in a non-metastatic breast cancer cohort using RMST function: a single-institution experience

Irina Niţă1,2, Cornelia Niţipir1,2, Ioana Anca Bădărău1

1. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
2. Medical Oncology Department, “Elias” University Emergency Hospital, Bucharest, Romania

Background and aim. Our aim is to examine the relationship between several factors (such as personal, tumoral or therapeutic) and the outcome of the patients. We analyzed a cohort of patients with early and locally advanced breast cancer (BC) using the restricted mean survival time (RMST). This value summarizes the treatment efficacy in terms of event-free time over a fixed period. Materials and method. We evaluated the prognostic values in 143 patients treated for early BC at the “Elias” University Emergency Hospital, Bucharest, Romania, and followed-up for a maximum of 36 months. The protocol was amended to include the personal factors, the levels of education and background, the clinical stage, the tumor aspects (grading, histology type or immunohistochemistry characteristics) and some aspects related to the treatment received. The methodology consisted of Kaplan-Meier analysis and RMST for the entire sample. The main endpoints of the study were overall survival (OS) and progression-free survival (PFS). Using “backward selection”, we analyzed only the variables that were statistically significant and influenced the prognostic of the patients. Results. The levels of education impacted both RMST OS (35.30 versus 26.70) and death HR (hazard ratio) in the group of patients with low educational levels. The clinically staged lymph node influenced both OS (p=0.05) and PFS (p=0.0006) for the patients with palpable or imaging proof of lymph node involvement of station 2 or 3. Both lower Ki67 and low tumor grade were associated with better prognosis in terms of OS and PFS for our patients’ cohort. Conclusions. RMST provides an intuitive and explicit way to express the effect of risk factors on OS and PFS in a cohort of non-metastatic BC patients. Independent predictors for the OS were the education level, with a 10.2-fold HR increase, and triple-negative breast cancer (TNBC), with a 6-fold HR increase, regardless of education level. Independent predictors for PFS were clinical tumor stage N2, N3, Ki67 value, high tumor grade and the basic level of CA15-3 marker.
Acknowledgment: This paper has been partially supported by the STAMINA project which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 883441.

Rectal stenoses of benign etiology with neoplastic evolution

V.M. Prunoiu, M.A. Marincaş, E. Brătucu, Ştefania Neicu, Maria-Manuela Răvaş, Laurenţiu Simion

“Carol Davila” University of Medicine and Pharmacy, Bucharest; “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania 

Idiopathic retroperitoneal fibrosis has preoccupied the surgical world since 1948, when the first case of ureteral stenosis following a retroperitoneal scleroinflammatory process of unknown cause was published by J. K. Ormond. By 1960, 82 cases had been reported in literature. The authors present two new personal cases of idiopathic retroperitoneal fibrosis, located exclusively in the pelvic compartment (subperitoneal) of the retroperitoneal space. The literature dedicated to this subject is reviewed, the current etiological theories are evoked, and the treatment opportunities are discussed.

Atypical spitzoid tumors in young patients. Evaluation and diagnosis

Luiza Purcari, Cristina Bădic, Roxana Potop, Daniela Stan, Anca Pîslariu, Cristian Iaciu, Cornelia Niţipir 

Medical Oncology Department, “Elias” University Emergency Hospital, Bucharest, Romania 

Background. The Spitz nevus and the spitzoid malignant melanoma represent the two ends of the spitzoid lesion spectrum. The atypical spitzoid neoplasias represent an ambiguous clinical category which includes lesions presenting both benign and malignant histologic characteristics. Therefore, these tumors remain a challenge for the pathologists, given the fact that a clear prediction of the future behavior of the tumor is difficult, if not impossible. Some tumors will metastasize and will have a poor prognosis, some will present no metastatic behavior and will have an indolent evolution, and some will metastasize modestly and exclusively to the locoregional lymph nodes. Case description. This paper presents a case of an atypical spitzoid tumor in a 21-year-old patient with no significant personal or familial family history which expressed borderline characteristics between benign and malignant lesions. The patient underwent SLNB, with a positive result for an isolated micrometastasis and the biopsy material was further tested for molecular and genetic abnormalities. Complete lymph node dissection was performed and consequent adjuvant treatment with immune checkpoint inhibitors was initiated. The case aims at emphasizing the challenges that these tumors imply in terms of diagnosis and further treatment. Conclusions. Borderline melanocytic tumors represent a challenge for the oncological field, due to their unpredictive behavior. Between the two concepts of primum non nocere and precaution is better than curing, it is important to take a collective decision, including patients, their families and the specialists with a high expertise level in this field. How far should reach the treatment choice is yet unknown and should be carefully decided upon. Seeking a second opinion is therefore indicated in these difficult to define cases. Further research is needed to better define predictive factors and to separate between histologic categories.

Radiotherapy, surgical intervention or induction chemotherapy – first treatment intent in cervical cancer, stage IB3?

Laura Florentina Rebegea 

Radiotherapy Department, “Sf. Ap. Andrei” Emergency Clinical Hospital, Galaţi; Medical-Clinical Department, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University of Galaţi; Research Center in the Field of Medical and Pharmaceutical Sciences, ReFORM-UDJ, 800010, Galaţi, Romania 

Cervical cancer still represents an important cause of morbidity and mortality, with all the progress achieved in screening, prevention, diagnostic and treatment. Concomitant chemoradiotherapy brings a benefit in the survival of cervical cancer patients. The standard treatment in stages IB2 – IVA consist in concomitant platinum chemotherapy and radiotherapy followed by brachytherapy, preferable image-guided (IGBT). The poor prognostic is correlated with tumor characteristics (dimensions more than 4 cm), histology, lymphovascular space invasion, and regional lymph node invasion. We present the case of a 42-year-old woman diagnosed with cervical cancer, stage IB3 FIGO; we also present the discussion about the first therapeutic intent within multidisciplinary committee for diagnostic and therapeutic course. We are trying to answer some questions regarding whether it is necessary and when is recommended hysterectomy after external radiotherapy, regarding the role of induction chemotherapy followed by surgical intervention in stage IB2 – IIB, and regarding the aspects related to fertility preservation in early stages. The discussions in the tumor board allow the recommendation of the most adequate treatment, the therapies’ sequentiality is decided by tumor’s and patient’s characteristics, the potential treatment’s late effects, the technical available resources and, last but not least, by patient’s opinion and the opinion of medical team who manages the case.

Rectal cancer with multiple metastases achieving complete remission – case presentation

Claudia Paraschiva Seliuc1, Elena Adriana Mateianu1, Adelina Silvana Dragomir1,2, Andreea Mihaela Radu3, Isabela Anda Komporaly1,2, Raluca Ioana Mihăilă1,2, Bogdan Georgescu1,2, Lidia Anca Kajanto1,2, Dana Lucia Stănculeanu1,2 

1. “Prof Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania
2. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
3. AMETHYST Radiotherapy Center, Bucharest, Romania

Colorectal cancer (CRC) is nowadays one of the three most common cancers all over the world, with high rates of mortality and morbidity not only in Western countries, but also in Romania. Even though the screening methods are widely available, more than 30% of patients have already distant organs or lymph node metastases when they are first diagnosed with colorectal cancer. We discuss the particularities of a stage IV rectal cancer case in a 62-year-old female patient. In the context of emergency surgery for stenotic rectal carcinoma, a Hartmann’s procedure was successfully performed, the tumor mass was pathologically confirmed to be a colorectal adenocarcinoma, moderately differentiated, and molecular biology detected no RAS mutations. Moreover, the histopathological exam revealed multiple peritoneal lymph node metastases, whereas the PET scan highlighted three different hepatic lesions which were metabolically active. Weighing the stage of the carcinoma, the molecular analysis and the performance status of the patient, multiple series with FOLFIRI chemotherapy in combination with weekly cetuximab were performed. After three years of treatment, the CT scans showed a partial remission of the disease, which was eventually followed by complete remission. The disease-free interval of one year was followed by the appearance of two new liver lesions for which new series with FOLFOX-4 and biweekly cetuximab were initiated. An adverse reaction of cetuximab developed by the patient after several months required a new approach of the case: introducing bevacizumab, along with the FOLFOX regimen. The patient is currently under this treatment. In recent years, the prognosis of CRC has been improving. Several treatment strategies are potential keys for improving the prognosis of patients with CRC. These include closer follow-up after resection and earlier detection of metastatic disease, improvement in chemotherapeutic regimens, and the enhancement of meetings held by multidisciplinary teams and tumor boards.


Ovarian cancer and late-onset anti-Yo positive paraneoplastic cerebellar degeneration – a case report

Cătălina-Georgiana Spac, Cristiana Ianculescu

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania

Introduction. Paraneoplastic neurological syndromes (PNS) are a rare group of disorders that occur in less than 1% of patients, as an immune response to a malignant tumor. Objectives. Paraneoplastic cerebellar degeneration (PCD) is characterised by an immune reaction against neural antigens in the cerebellum that can occur in gynecological malignancies and which causes a loss of Purkinje cells and, subsequently, cerebellar dysfunction. PCD has a mediocre prognosis; a temporary improvement can be obtained with corticosteroid treatment. Materials and method. We present the case of a 66-year-old female patient who presented with abdominal distention and pelvic pain. A CT exam showed a 45/30 mm uterine mass and ascites. An omentectomy, with a complete hysterectomy and bilateral anexectomy, was conducted. The histology revealed a high-grade ovarian carcinoma. The patient followed chemotherapy treatment with paclitaxel and carboplatin. Four years later, in November 2020, the patient presented with ataxia, dysarthria and mild dysphagia for liquids. A brain MRI did not reveal any mass lesions or signs of stroke or atrophy. Results. A blood test for the detection of anti-Yo antibodies was performed, with elevated results, confirming the diagnosis of PCD. The patient followed an immunosuppressive corticosteroid treatment. At the next neurological examen, the patient presented a mild improvement of the neurological symptoms. Conclusions. PCD is usually diagnosed prior to the appearance of a malignant tumor. In this case report, we present the case of a patient who developed PCD four years after the diagnosis of ovarian cancer. Mild neurological improvement has been achieved following corticosteroid treatment.

Cardiovascular risk assessment in patients with differentiated thyroid cancer undergoing radioiodine therapy

Adina Elena Stanciu1, Lucica Mădălina Bolovan1, Camelia Frăsineanu1, Marcel Marian Stanciu2, Andreea Verzia1, Tincuţa Tegus1, Claudia Nicorovici1, Daniela Dragomir1, Aurelia Dumitrescu1, Anca Zamfirescu1

1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania
2. Politehnica University of Bucharest, Romania

Objective. In the last decade, an increasing number of studies have estimated the cardiovascular risk in different populations, mainly using the Framingham risk score (FRS) and Systematic COronary Risk Evaluation (SCORE). The accuracy of these risk scores for predicting cardiovascular events in differentiated thyroid cancer (DTC) is not well established, despite a high prevalence of hypertension, dyslipidemia and cardiovascular disease among DTC patients. The current study aimed at comparing the FRS and SCORE models in predicting cardiovascular events in patients with DTC undergoing radioiodine (131I) therapy. Methodology. Thirty-three patients with DTC (mean age 55.9 ± 10.7 years old) and eight patients with DTC associated with type 2 diabetes mellitus (DTC+T2DM) (mean age 65 ± 9.8 years old) were included in the study. FRS and SCORE questionnaires incorporated risk factors such as age, sex, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, and smoking status. Cardiac function was assessed by echocardiography. Results. DTC+T2DM patients had a higher cardiovascular risk than that calculated in DTC patients without T2DM according to FRS and SCORE tools (11.4±9.7 versus 10.7±9.5, p=0.27, and 4.9±2.7 versus 2.3±1.8, p=0.02, respectively). Of the two cardiovascular risk assessment models, only SCORE was associated with the left ventricle ejection fraction (LVEF) in the DTC+T2DM group (r=-0.75, p=0.03). The high cumulative activity of 131I was independently correlated with LVEF in patients with DTC without T2DM (r=-0.49; p<0.01). Conclusions. Our results indicate that DTC patients have an increased cardiovascular risk. This risk can be estimated by using the SCORE model in patients with coexisting T2DM. The mechanisms that mediate cardiovascular risk in these patients seem to involve the systemic chronic inflammation characteristic of T2DM. In patients with DTC without T2DM exposed to high cumulative radiation doses of 131I, the cardiovascular risk assessment tool should contain the total activity of 131I administered per patient. 
Funding Acknowledgement This work was supported by a grant from the Romanian Ministry of Education and Research, CCCDI – UEFISCDI, project number PN-III-P2-2.1-PED-2019-3313, within PNCDI III.

The role of maintenance therapy in ovarian cancer – updated literature review

Dana Lucia Stănculeanu 

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest; “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania 

The purpose of this review is to summarize the most recent data supporting the use of maintenance therapy in advanced epithelial ovarian cancer (OC) treatment, which has been developed to prevent disease recurrence after primary therapy. Poly (ADP-ribose) polymerase inhibitors (PARPi) and anti-angiogenic agents dominate the landscape of maintenance treatment. PARPi therapy has been approved in the treatment of high-grade serous OC in the settings of platinum-sensitive recurrence, as maintenance single agent treatment after standard first-line chemotherapy, based on the results of: Study 19, SOLO-3 and SOLO-2 (Olaparib), QUADRA and NOVA (Niraparib), ARIEL-2 and ARIEL-3 (Rucaparib). At the molecular basis, PARPi eliminate the remaining tumor cells before they go subclonal or increase clonality index, therefore it is best to start the administration at the time of best response. Recent practice-changing randomized clinical trials (SOLO-1, PAOLA-1, VELIA and PRIMA) demonstrated significant improvements in progression-free survival (PFS) driven by the incorporation of PARPi (olaparib, olaparib+bevacizumab, veliparib and niraparib) as standard front-line maintenance therapy. The benefit was not only observed in women with BRCA mutations and homologous recombination deficiency (HRD), but also in those with BRCA wild type and even non‐HRD. Biomarker testing is extremely important, but the selection of maintenance is based also on clinical and financial factors. Regarding the anti-VEGF antibody bevacizumab, the final analysis of the GOG-218 trial did not reveal overall survival differences for patients who received anti-angiogenic maintenance therapy compared with chemotherapy alone, despite the improvement in PFS. However, olaparib+bevacizumab represents an option for BRCA mutant or HRD-positive patients in front-line therapy. Although PARPi are currently established as maintenance therapies in recurrence settings and front line, there are still unanswered questions that further trials will address, such as the role of maintenance in PARPi-exposed patients and possible PARPi combinations. There is also a need for the development of more specific and sensitive predictive biomarkers for PARPi maintenance therapy and also to investigate their response in other molecular phenotypes of OC. 

The benefits of co-testing in national screening programs in cervical cancer

N. Suciu1,2, D. Creţoiu1,2, Adriana Irina Ciuvică1, Ioan Dumitru Suciu2, T.A. Georgescu1,2, Romeo Micu

1. “Alessandrescu-Rusescu” National Institute for Mother and Child Care, Bucharest, Romania
2. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
3. “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

The ideal screening test for cervical cancer is the one that has the ability to correctly and effectively identify all patients with premalignant changes, while at the same time exclude those without changes. Unfortunately, no test is perfect. Cervicovaginal cytology is the traditional screening method, independently described by Aurel Babeş and George Papanicolaou in 1927 and 1928, respectively. Data from the scientific literature report a relatively low sensitivity for conventional cytology, ranging from 20% to 50%, and a specificity in the identification of HSIL lesions that can reach up to 90%, based on the experience of the examiner. Given the mechanism of cervical carcinogenesis, the detection of human papillomavirus (HPV) infection is currently one of the main screening alternatives, especially in the context of the dramatic cost reductions which occurred in the recent years. HPV testing may have a sensitivity of up to 17% higher compared to classical cytology, but the latter is known for a slightly increased specificity compared to HPV testing. Although HPV testing is more effective in identifying high-grade lesions, it generates more indications for colposcopy. However, a negative HPV result is more encouraging than a negative cytological result, because the cytological examination is more likely to be false negative, which would lead to delays in the application of appropriate treatment. Regardless of age group stratification, cytological and HPV co-testing have a much higher sensitivity (>92%) in the identification of premalignant lesions compared to isolated testing.

Is there any room for axillary lymph node dissection in breast cancer in the sentinel lymph node biopsy era?

Angela Şandru1, Silviu Voinea1,2, Lăcrămioara Borangic1, Cristina Capşa1, Alexandru Blidaru1,2 

1. “Prof Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania
2. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

Axillary lymph node dissection (ALND) has been and yet remains an important part of breast cancer treatment. Although the development and refinement of the sentinel lymph node biopsy (SLNB) technique have revolutionized surgery for several locations of cancerous disease, the complete lymph node dissection of regional basins still retains an important place in the therapeutic armamentarium. SLNB in clinical node negative breast cancer patients provides the same prognostic information as ALND, but with significantly lower morbidity. Several randomized controlled trials conducted over the past 20 years have established SLNB as the gold standard in the treatment of early breast cancer. ALND is a standardized procedure with clear, well-defined benchmarks and boundaries. An accurate technique and a good knowledge of the axillary anatomy are indispensable conditions for achieving a complete and correct axillary clearance. Unfortunately, the application of a careful and meticulous dissection technique is not enough to guarantee the absence of complications, but only their limitation. As a consequence of advances in interventional radiology, oncological treatments and molecular biology, lymphadenectomy indications have evolved, adapted to the new concepts, apparently narrowed, but the procedure still holds an indisputable role in breast cancer treatment. 

Challenges in vulvar carcinoma surgery

Silviu Voinea1,2, Angela Şandru1, Cristian Bordea1,2, Lăcrămioara Borangic1, Raluca Nicolaescu1, Cristina Capşa1, Alexandru Blidaru1,2

1. “Prof Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania
2. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

Vulvar cancer is a rare neoplasm, representing only 1% of all cancers of the female reproductive system, and represents a challenge for the surgeon and radiotherapist through the difficult management of advanced cases. Locoregionally advanced vulvar cancer (stage III) is characterized by the presence of large tumors, often ulcerated, superinfected, which may extend to the lower urethra, vagina or anal canal, and also by inguinofemoral metastatic adenophaties. These cases raise issues of surgical technique and tactics to address them, because vulvectomy is very difficult to perform, it is bloody and associates the resection of the urethra and the lower anal canal and external anal sphincter. The reconstruction of the perineum is difficult and tension sutures should be avoided, due to the high risk of wound dehiscence, and sometimes retractile scarring. The main postoperative complications are: bleeding, pubic edema, local infection and wound dehiscence, lymphocele. This paper highlights the technical features and difficulties of locoregionally advanced vulvar cancer surgery, as well as the solution we have adopted, and also the morbidity associated with the radiosurgical treatment. The therapeutic indication for these cases must be properly determined and correlated with tumor extension and patients’ performance status. 

Which are the changes in cervical cancer staging, what justified them and when do they affect the surgical treatment?

Silviu Voinea1,2, Angela Şandru1, Lăcrămioara Borangic1, Alexandru Blidaru1,2

1. “Prof Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania
2. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

Cancer staging is an essential step in providing a coherent and effective treatment. The stratification of disease anatomical extension into categories with similar prognostic significance is a constantly evolving process, which adapts to the advances in other branches of medicine. This is why the American Joint Committee on Cancer (AJCC) in collaboration with the Union for International Cancer Control (UICC) regularly review the staging system, on average every 5-7 years, based on collected survival data, and findings in radiology, pathology and molecular medicine. Although the last edition of AJCC, the eighth, came into use on the 1st of January 2018, for the first time, after less than three years, a new version for cervical cancer was introduced in practice. The ninth version, valid for cervical cancers diagnosed beginning with the 1st of January 2021, brings significant changes for stages I and III, with implications in the therapeutic approach.