Long-Term Results of IFRT vs. ISRT in Infradiaphragmal Fields in Aggressive Non-Hodgkins's Lymphoma Patients-A Single Centre Experience.

(1) Background: This study aimed to examine the difference in efficacy and toxicity of involved-field (IFRT) and involved-site radiotherapy (ISRT) fields in infradiaphragmal aggressive non-Hodgkin lymphoma patients. (2) Methods: In total, 140 patients with infradiaphragmal lymphoma treated between 2003 and 2020 were retrospectively evaluated. There were 69 patients (49%) treated with IFRT, and 71 (51%) patients treated with ISRT. The median dose in the IFRT group was 36 Gy, (range 4-50.4 Gy), and in the ISRT group, it was 30 Gy (range 4-48 Gy). (3) Results: The median follow-up in the IFRT group was 133 months (95% CI 109-158), and in the ISRT group, it was 48 months (95% CI 39-57). In the IFRT group, locoregional control was 67%, and in the ISRT group, 73%. The 2- and 5-year overall survival (OS) in the IFRT and ISRT groups were 79% and 69% vs. 80% and 70%, respectively (p = 0.711). The 2- and 5-year event-free survival (EFS) in the IFRT and ISRT groups were 73% and 68% vs. 77% and 70%, respectively (p = 0.575). Acute side effects occurred in 43 (31%) patients, which is more frequent in the IFRT group, 34 (39%) patients, than in the ISRT group, 9 (13%) patients, p > 0.01. Late toxicities occurred more often in the IFRT group of patients, (10/53) 19%, than in the ISRT group of patients, (2/37) 5%, (p = 0.026). (4) Conclusions: By reducing the radiotherapy volume and the doses in the treatment of infradiaphragmatic fields, treatment with significantly fewer acute and long-term side effects is possible. At the same time, efficiency and local disease control are not compromised.

Efficacy and toxicity of infradiaphragmal radiotherapy fields in lymphoma patients: a single-centre experience.

PURPOSE: Data on efficacy and toxicity of infradiaphragmal radiotherapy fields in lymphoma patients are scarce. We therefore performed this retrospective study to analyse our experience with radiotherapy exclusively to infradiaphragmal fields. MATERIALS AND METHODS: we retrospectively evaluated 101 patients treated between 2003 and 2014. Median dose was 36 Gy, range 4 to 54 Gy. Medium dose per fraction was 2 Gy, range 1.5 to 7 Gy. RESULTS: After a median follow-up of 66 months (range 1-211 months), we observed lymphoma recurrence in 38 patients (38%), five in the RT field and 33 out-of-field. Recurrences were significantly more frequent in the salvage group (17 out-of-field and 4 in-field in 31 patients) than in adjuvant group (16 out-of-field and 1 in-field in 70 patients; p < 0.001). The 2-, 5- and 10-year event-free survival (EFS) rates were 62%, 56% and 54%. The 2-, 5- and 10-year overall survival (OS) rates for the entire group of patients are 73%, 60% and 54%, respectively. Acute side effects occurred in 43 (43%) patients, most frequent gastrointestinal in 26 (26%) patients. Late side effects occurred in 12 (12%) of all patients, 6 of 23 (26%) followed up for more than 10 years. Six patients developed secondary cancers, four gastrointestinal disturbances, two diabetes mellitus and three renal failure. CONCLUSION: Radiotherapy is an effective and safe treatment option for patients with infradiaphragmatic lymphoma providing excellent local disease control with minimal late toxicity. Infradiaphragmatic lymphoma localization should not be regarded as a contraindication for use of radiotherapy. However, patients should be monitored for a secondary malignancy.

INFRADIAPHRAGMAL RADIOTHERAPY IN PATIENTS WITH LYMPHOMA: VOLUME DEFINITION AND SIDE EFFECTS.

- Lymphomas are very radiosensitive and radiotherapy (RT) was the first treatment modality that enabled cure. It is the most effective single modality for local control of lymphomas. However, as a local form of treatment, curative intention is only possible if all lymphoma tissue can be incorporated in the volume to be irradiated with the prescribed total irradiation dose. That is why RT is a single modality only in early stage of nodular lymphocyte predominance Hodgkin's lymphoma and low grade non-Hodgkin's lymphoma. In most patients, RT can be used as consolidation therapy after chemotherapy or as salvage after failure of chemotherapy. In the past two decades, irradiation techniques have been improved in order to spare critical tissues and reduce toxicity. Although effective, RT is a neglected modality of treatment because of the appearance of new drugs and fear of side effects after irradiation. Radiation has been shown to be effective in the treatment of all stages and forms of lymphoma. Study data are still mostly derived from patients that received supradiaphragmal RT; therefore, there is no agreement about the best management approach in patients with infradiaphragmal lymphoma.

Giant low-grade primary myofibroblastic sarcoma of the posterior chest wall.

Primary myofibroblastic sarcoma is an extremely rare, highly malignant neoplasm, and only few cases had been reported in the literature worldwide. In the present study, we report an unusual case of a low-grade myofibroblastic sarcoma located in the posterior chest wall with intrathoracic propagation and discuss its clinical and pathological features.

Significant Clinical Benefit of Pemetrexed-based Chemotherapy for Advanced Diffuse Malignant Peritoneal Mesothelioma: A Case Presentation.

Diffuse malignant peritoneal mesothelioma (DMPM) is generally an understudied disease, largely because most molecular and clinical studies of mesothelioma have been conducted in patients with the more common malignant pleural mesothelioma. We present the case of a 45-year-old male that initially presented with abdominal discomfort and ascites. Diagnostic workup revealed advanced DMPM. Bimodal treatment was stared with cytoreductive surgery and hyperthermic intraperitoneal perfusion with chemotherapy procedure, followed by pemetrexed systemic monotherapy. After the disease progression, and because of a very good previous treatment response to pemetrexed, we decided to rechallenge systemic pemetrexed, along with the introduction of cisplatin. Although the intent behind systemic treatment was at first solely palliative, overall survival after the initial diagnosis was 50 months. Treatment based on rechallenging pemetrexed with or without cisplatin in patients with advanced DMPM can result in a quite satisfactory disease control and symptom management.

High-dose ifosfamide and mitoxantrone (HDIM) in patients with relapsed or refractory Hodgkin's lymphoma.

Relapsed/refractory Hodgkin's lymphoma (HL) is treated with salvage chemotherapy and autologous stem cell transplantation (ASCT). Optimal chemotherapy is unknown. We retrospectively analyzed outcomes of 58 patients treated with 2 cycles of high-dose ifosfamide and mitoxantrone (HDIM). HDIM consisted of ifosfamide 5 g/m(2)/day and MESNA 5 g/m(2)/day in continuous 24-h infusion (days 1 and 2), MESNA 2.5 g/m(2) over 12 h (day 3), and mitoxantrone 20 mg/m(2) (day 1) administered every 2 weeks. Stem cells were collected after the first cycle. Responding patients proceeded to ASCT. Toxicity was acceptable. Stem cell mobilization was successful in 96 % of patients. Overall response rate was 74 % (89 % in relapsing and 45 % in refractory patients) with 31 % complete remissions. After a median follow-up of 54 months, 5-year event-free survival was 56 % (69 % for relapsing and 35 % for refractory patients), and 5-year overall survival was 67 % (73 % for relapsing and 55 % for refractory patients). Significant adverse prognostic factors were refractoriness to previous therapy and HDIM failure. No differences in outcomes were noted between patients with early and late relapses or between complete and partial responders. HDIM is a well-tolerated and effective regimen for relapsed and refractory HL with excellent stem cell mobilizing properties. Patients failing HDIM may still benefit from other salvage options.

Gastroenteropancreatic neuroendocrine tumour arising in Meckel's diverticulum coexisting with colon adenocarcinoma.

Although colon cancer is the third most common cause of cancer-related death worldwide, the prevalence of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) remains rare. To date, very few cases of GEP-NETs within Meckel's diverticulum and synchronous colorectal cancer have been reported. Although the coexistence of these two tumour types is uncommon, it is important to be aware of their disease patterns. We present a rare case of a patient with an intestinal GEP-NET arising in Meckel's diverticulum coexisting with metastatic colon adenocarcinoma, and we discuss the clinical manifestations and the diagnostic procedures and treatment modalities used. This case report underlines the importance of being aware of this particular coexistence, as well as the unlikely metastatic spread of GEP-NETs and the importance of a multidisciplinary approach to cancer treatment. Finally, individualizing the treatment according to the stages of the primaries will result in durable cancer control, particularly in synchronous double malignancy.

Clinical significance of immunohistochemical expression of cancer/testis tumor-associated antigens (MAGE-A1, MAGE-A3/4, NY-ESO-1) in patients with non-small cell lung cancer.

AIMS AND BACKGROUND: This paper deals with the clinical significance of the immunohistochemical expression of MAGE-A1, MAGE-A3/4 and NY-ESO-1 antigens in patients with non-small cell lung cancer (NSCLC). METHODS AND STUDY DESIGN: The study included 80 patients with NSCLC (40 with adenocarcinoma, 40 with squamous cell carcinoma) who had undergone surgery. MAGE-A1 and MAGE-A3/4 antigen expression was determined by an immunohistochemical method using the monoclonal antibody 57B, and NY-ESO-1 antigen expression was determined with the addition of the B9.8.1.1 antibody. The expression of these antigens was compared with the clinicopathological features of the tumors and the survival of the patients. RESULTS: MAGE-A1, MAGE-A3/4 and NY-ESO-1 were expressed in 17.3%, 44.4% and 18.5% of NSCLC patients, respectively. A statistically higher immunohistological expression rate of MAGE-A3/4 was found in squamous cell carcinoma (P <0.001) and a significantly higher amount of tumor necrosis was observed in tumors with MAGE-3 expression (P = 0.001), but no correlation with positive lymph nodes was found. There was a statistically significant correlation between MAGE-A1 expression in adenocarcinoma and the presence of tumor necrosis (P = 0.05). Furthermore, there was a significant correlation between NY-ESO-1 expression and positive lymph nodes in adenocarcinoma, but not in squamous cell carcinoma. No statistically significant difference in patient survival was found with regard to tumor type and the observed histopathological characteristics except tumor size. Statistically significantly better survival was found in the group of patients with adenocarcinomas who had positive expression of MAGE-A3/4 (P = 0.012). CONCLUSIONS: This study demonstrated that the expression of MAGE-A3/4 antigen might be a valuable prognostic factor regarding survival in patients with NSCLC.

[Lymphoma diagnosis and treatment - second Croatian consensus]. / Dijagnostika i lijecenje limfoma - drugi hrvatski konsenzus.

New, extended and modernized recommendations for diagnostics and treatment of lymphomas were accepted at a meeting held in March 2012 with the participation of major Croatian experts. They encompass morphological, radiological and nuclear diagnostics, systemic treatment, radiotherapy and follow-up of most tumors of lymphoid tissues occurring in adults. The recommendations were agreed upon by consensus. Reporters presented data and suggested recommendations which had been first discussed in working groups and then agreed upon on the plenary session.

Leptomeningeal and intramedullary metastases of glioblastoma multiforme in a patient reoperated during adjuvant radiochemotherapy.

Despite huge advances in medicine, glioblastoma multiforme (GBM) remains a highly lethal, fast-growing tumour that cannot be cured by currently available therapies. However, extracranial and extraneural dissemination of GBM is extremely rare, but is being recognised in different imaging studies. To date, the cause of the GBM metastatic spread still remains under discussion. It probably develops at the time of intracranial progression following a surgical procedure. According to other hypothesis, the metastases are a consequence of spontaneous tumour transdural extension or haematogenous dissemination. We present a case of a 59-year-old woman with symptomatic leptomeningeal and intramedullary metastases of GBM who has been previously surgically treated with primary subtotal resection and underwent a repeated surgery during adjuvant radiotherapy and chemotherapy with temozolomide. Today, the main goal of surgery and chemoradiotherapy is to prevent neurologic deterioration and improve health-related quality of life. With this paper, we want to present this rare entity and emphasise the importance of a multidisciplinary approach, a key function in the management of brain tumour patients. The prognosis is still very poor although prolongation of survival can be obtained. Finally, although rare, our case strongly suggests that clinicians should be familiar with the possibility of the extracranial spread of GBM because as treatment improvements provide better control of the primary tumour and improving survival, metastatic disease will be increasingly encountered.

Symptomatic cardiac metastases of breast cancer 27 years after mastectomy: a case report with literature review--pathophysiology of molecular mechanisms and metastatic pathways, clinical aspects, diagnostic procedures and treatment modalities.

Metastases to the heart and pericardium are rare but more common than primary cardiac tumours and are generally associated with a rather poor prognosis. Most cases are clinically silent and are undiagnosed in vivo until the autopsy. We present a female patient with a 27-year-old history of an operated primary breast cancer who was presented with dyspnoea, paroxysmal nocturnal dyspnoea and orthopnoea. The clinical signs and symptoms aroused suspicion of congestive heart failure. However, the cardiac metastases were detected during a routine cardiologic evaluation and confirmed with computed tomography imaging. Additionally, this paper outlines the pathophysiology of molecular and clinical mechanisms involved in the metastatic spreading, clinical presentation, diagnostic procedures and treatment of heart metastases. The present case demonstrates that a complete surgical resection and systemic chemotherapy may result in a favourable outcome for many years. However, a lifelong medical follow-up, with the purpose of a detection of metastases, is highly recommended. We strongly call the attention of clinicians to the fact that during the follow-up of all cancer patients, such heart failure may be a harbinger of the secondary heart involvement.

[Hormonal therapy of prostate cancer: are there any dilemmas left?]. / Hormonska terapija raka prostate: ima li jos dilema?

The strategy for treating prostate cancer patients depends on the assessment of disease extent, assessment of the risk of disease relapse, assessment of life expectancy, comorbidities, affinities and life-style. Since the activity and survival of prostate cancer cells is at least initially dependent on androgen stimulation, hormonal therapy is one of the several standard treatment modalities. Hormonal therapy is aimed at decreasing this androgen stimulation either by lowering androgen production or by blocking receptor binding. Hormonal therapy is in fact androgen-suppressive therapy (AST) or androgen-deprivation therapy (ADT). If effective, it results in the lack of cancer cell stimulation, thus causing their apoptosis and consequently decline in tumor growth and size. Hormonal therapy is used as a first-line treatment modality for metastatic disease. In addition to this indication, hormonal therapy is also used as an adjunct to radiotherapy with curative intent for patients with non-metastic disease but having an intermediate and high risk of disease relapse. In combination with radiotherapy, hormonal therapy can be applied before, concomitantly and after radiotherapy for the duration of 6 months or 2 to 3 years depending on the risk estimation. Regarding hormonal therapy, it can be applied in combination with other treatments, in several ways, and sometimes there might be several options available. This possible lack of a specific recommendation is a consequence of the fact that there is a limited number of adequate clinical studies which, moreover, may have yielded inconsistent results sometimes simply due to the patients' heterogeneity. Moreover, thanks to the newer and better diagnostic methods enabling the discovery of prostate cancer in earlier disease stages, as well as to the more effective treatments, there is also a prolongation of relapse-free survival and possibly of overall survival in patients having metastic disease. Consequently, the results of earlier clinical studies might no longer be applicable to the new "generations" of upcoming patients. As regards this improved survival, issues of patient's quality of life and possible side-effects of hormonal therapy are also becoming increasingly relevant because hormonal adverse events are time-dependant and tend to increase in severity with prolongation of hormonal manipulation. Therefore, this paper aims to give an overview of the more recent findings, indications and observations regarding hormonal therapy.

[Multiple primary malignancies]. / Multipli primarni tumori.

Multiple primary malignancies, metachronous or synchronous, in a single patient are relatively rare event with the increase of incidence in recent decades. The aim of this research is to study their incidence in patients hospitalized at the Division of Radiotherapy, Department of Oncology, University of Zagreb, School of medicine, University Hospital Centre Zagreb from 2003 to 2009. The incidence of multiple primary malignancies was 2.4%. Among 103 patients, 97 had two, and 6 three primary tumors. Eighty-three cases were metachronous, while 20 cases were synchronous malignancies. The frequency was higher in females than males and their age at diagnosis of tumors was younger than in males. The most common tumor combinations in males were: prostate cancer-digestive system malignancy (especially colorectal cancer) and viceversa, and hematological malignant tumors-digestive system malignancy; while in women there were: breast cancer-cancer of contralateral breast and hematological malignant tumors (especially lymphoma non Hodgkin)-breast cancer. The incidence of multiple primary malignancies is expected to increase due to the better screening programs for early detection of malignancies as well as considerable improvement in their treatment and longer life expectancy.

Adjuvant therapy after radical surgery of cervical cancer: Zagreb experience.

The results of the analysis of the treatment of 72 patients with carcinoma of the uterine cervix are presented. Seventy-two patients with Stage IB1 carcinoma of the cervix underwent a radical hysterectomy and pelvic lymphadenectomy. The low-risk group includes the patients without unfavourable prognostic factors that were treated by surgery alone. The high-risk group included women with pelvic node metastases, clinical tumour size greater than 3.0 cm, depth of stromal invasion greater than 1/3 of the cervical wall, Grade 3 tumours and the presence of lympho-vascular space involvement. High-risk patients received whole pelvic radiotherapy between two and four weeks following surgery. Thirty-four patients (47.2%) were in the low-risk group and thirty-eight patients (52.8%) were in the high-risk group. Locoregional recurrences were diagnosed in three cases (8.8%) in the surgery group and in four patients (10.5 %) assigned to postoperative radiotherapy. The incidence of distant metastases was 2.9% in the group treated by surgery alone and 5.3% in the group treated by surgery and radiotherapy. Overall survival at five years was 91.2% in the low-risk group and 89.5% in the high-risk group of patients. Five-year overall survival, locoregional and distant metastases were similar in the low-risk and high-risk groups of patients, which emphasizes the value of whole pelvic radiation in patients with one or more unfavourable prognostic factors after radical surgery in Stage IB1 cervical cancer

[Primary central nervous system lymphoma--a single center experience]. / Primarni limfomi sredisnjega zivcanog sustava--prikaz vlastitih iskustava.

Primary lymphoma of central nervous system (PCNSL) represents a distinct form of extranodal non-Hodgkin's lymphoma localized to central nervous system. We collected data retrospectively of 20 patients with PCNSL treated at Division of Hematology of UHC Zagreb in the last eight years. A total of 13 patients received high dose methotrexate (4 g/m2) while others received other chemotherapy regimens or radiotherapy only. Complete remission rate was 40% and estimated 2-years actuarial survival was 30%. There were no treatment related deaths or significant severe adverse events. Our results are satisfactory in patients younger than 60 years, especially if treated with high dose methotrexate. Older patients, who represent majority of the patients, have dismal prognosis irrespective of treatment modality.

Allogeneic stem cell transplantation in treatment of aggressive lymphomas: case series.

AIM: To assess the outcome of allogeneic stem cell transplantation in patients with aggressive lymphoma. METHODS: Between 1991 and 2002, 22 patients with aggressive lymphoma in advanced phase of the disease underwent allogeneic stem cell transplantation at the Division of Hematology, Zagreb University Hospital Center. Seventeen patients received stem cells from the bone marrow. Eighteen patients underwent total body irradiation and received cyclophosphamide for conditioning, whereas the rest of the patients received busulfan and cyclophosphamide (n=2) or chemotherapeutic protocol combining carmustine, melphalan, etoposide, and cytarabine (BEAM regimen) (n=2). All patients received cyclosporin and short methotrexate for the prophylaxis of graft-versus-host disease (GVHD). RESULTS: Three months after allotransplantation, 17 patients had complete remission, 3 patients had active disease, and the outcome in 2 patients was early death. Nine patients were alive and in complete remission for 4 to 124 months, whereas 13 patients died (8 because of disease progression and 3 because of GVHD and infection). The probability of overall survival at 4 years was 47%. CONCLUSION: Allogeneic transplantation is an effective therapy for advanced aggressive lymphoma. Because of high treatment-related toxicity and mortality, prospective trials are needed to asses the best time when to apply this treatment.