Radiotherapy alone as a method of treatment for sinonasal mucosal melanoma: A report based on six cases and a review of current opinion.

OBJECTIVES: Radiotherapy in patients with sinonasal mucosal melanoma (SNMM) was given as alternative treatment to surgery in cases with advanced, inoperable tumors or those not eligible for surgery. We presented the outcomes for patients with SNMM treated with radiotherapy alone. MATERIAL AND METHODS: The retrospective review of 6 consecutive SNMM (nasal cavity - 4 pts. and paranasal sinus - 2 pts.) patients (3 males and 3 females at mean age 64 years) treated between 2008 and 2016 was presented. The stage of disease was: T3 (1 pt.), T4a (3 pts.), T4b (2 pts.); with N0 and M0 in all patients. All patients underwent definitive primary photon radiotherapy (IMRT) alone; dose 66-72 Gy was delivered in 22-24 fractions given in 5 fractions (3 Gy) a week. RESULTS: The complete remission was observed in all our patients but only one patient survived 5 years without disease. Five patients died due to multiple distant metastases; two of those patients developed associated local recurrence 7-8 months after radiotherapy. CONCLUSION: SNMM has a poor prognosis due to its high metastatic potential. Based on our numerically small report and data from literature we concluded that primary radiotherapy alone assured complete remission and even 5-year disease-free survival in only a few individual patients.

Current treatment options of brain metastases and outcomes in patients with malignant melanoma.

The prognosis for patients with melanoma who have brain metastases is poor, a median survival does not exceed 4-6 months. There are no uniform standards of treatment for patients with melanoma brain metastases (MBMs). The most preferred treatment approaches include local therapy - surgical resection and/or stereotactic radiosurgery (SRS). The role of whole brain radiotherapy (WBRT) as an adjuvant to local therapy is controversial. WBRT remains a palliative approach for those patients who have multiple MBMs with contraindications for surgery or SRS, or/and poor performance status, or/and very widespread extracranial metastases. Corticosteroids have been used in palliative treatment of MBMs as relief from symptoms related to intracranial pressure and edema. In recent years, the development of new systemic therapeutic strategies has been observed. Various modalities of systemic treatment include chemotherapy, immunotherapy and targeted therapy. Also, multimodality management in different combinations is a common strategy. Decisions regarding the use of specific treatment modalities are dependent on patient's performance status, and the extent of both intracranial and extracranial disease. This review summarizes current treatment options, indications and outcomes in patients with brain metastases from melanoma.

Pure and Mixed Mucinous Carcinoma of the Breast: A Comparison of Clinical Outcomes and Treatment Results.

Mucinous breast carcinoma (MBC) carcinoma represents approximately 1-6% of all malignant breast carcinoma and is divided into pure (PMBC) and mixed (MMBC) subtypes. This study presents the comparison of clinical characteristics and treatment results in 70 patients with PMBC and 40 patients with MMBC, treated at a single institution during 25 years. Performed analyses showed that only nodal status was different in both subtypes. Patients with MMBC showed a significantly higher incidence of axillary nodal metastases in comparison to PMBC (25% versus 10%, respectively). Instead, the 10-year disease-free survival rate was significant higher in PMBC than MMBC (85.7% versus 65%, p < 0.02, test log rank). Authors own observations and data from literature proved that MMBC should be considered as subtypes of mucinous breast cancer.

Evaluation of intraocular proton beam irradiation complications after choroidal melanoma treatment. / [Ocena wewnatrzgalkowych powiklan po terapii protonowej czerniaków naczyniówki].

Purpose: The aim of the research was to evaluate of intraocular complications after proton beam therapy of choroidal melanomas Material and methods: A total 105 patients (48 female and 57 male) from Department of Ophthalmology and Ocular Oncology of University Hospital in Cracow, who received proton beam radiation due to choroidal melanoma were enrolled. The mean age was 52.3 years (51.8 y. in females, 52.6 y. in males). Total irradiation dose was 60 cGy and it was applied in 4 fractions per 15 cGy (on 4 consecutive days). We evaluated the incidence of complications classifying patients by age, tumor location, tumor thickness, longitudinal and transversal basal diameter and follow-up period, which ranged between 5 and 57 months. Results: Complications of intraocular irradiation were observed in 33 out of 105 treated patients. Retinopathy occurred in 18 cases, including 4 patients with macular edema. Neuropathy was confirmed in 8 patients, secondary glaucoma in 6 cases; we noted 9 cases of initial or progress existing cataract, 4 cases of dry eye syndrome and 1 patient with central retinal vein occlusion. A statistically significant positive correlation was demonstrated between the length of the follow-up period and the incidence of complications, which were more common and more severe with the longer follow-up period. There was no statistically significant correlation between the incidence of complications and patient's age, tumor location, tumor thickness as well as longitudinal and transversal basal diameter. Conclusion: All forms of radiation therapy used in intraocular tumors are associated with some risk of complications; proton beam radiotherapy is not free of that risk, either.

Systemic treatment of non-small cell lung cancer brain metastases.

In the systemic treatment of brain metastases from non-small cell lung cancer (BMF-NSCLC) chemo- and targeted therapy are used. Response rates after platinum-based chemotherapy, range from 23% to 45%. Development of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs): gefitinib or erlotinib, was an improvement in treatment of advanced NSCLC patients. EGFR mutations are present in 10-25% of NSCLC (mostly adenocarcinoma), and up to 55% in never-smoking women of East Asian descent. In the non-selected group of patients with BMF-NSCLC, the overall response rates after gefitinib or erlotinib treatment range from 10% to 38%, and the duration of response ranges from 9 to 13.5 months. In the case of present activating EGFR mutation, the response rate after EGRF-TKIs is greater than 50%, and in selected groups (adenocarcinoma, patients of Asian descent, never-smokers, asymptomatic BMF-NSCLC) even 70%. Gefitinib or erlotinib treatment improves survival of BMF-NSCLC patients with EGFR mutation in comparison to cases without the presence of this mutation. There is no data on the activity of the anti-EML4-ALK agent crizotinib. Bevacizumab, recombinant humanised monoclonal antibody anti-VEGF, in the treatment of advanced non-squamous NSCLC patients is a subject of intense research. Data from a clinical trial enrolling patients with pretreated or occult BMF-NSCLC proved that the addition of bevacizumab to various chemotherapy agents or erlotinib is a safe and efficient treatment, associated with a low incidence of CSN haemorrhages. However, the efficacy and safety of bevacizumab used for therapeutic intent, regarding active brain metastases is unknown.

Methods and results of locoregional treatment of brain metastases in patients with non-small cell lung cancer.

This article presents methods and results of surgery and radiotherapy of brain metastases from non-small cell lung cancer (BMF-NSCLC). Patients with single BMF-NSCLC, with Karnofsky score ≥ 70 and controlled extracranial disease are the best candidates for surgery. Stereotactic radiosurgery (SRS) is recommended in patients with 1-3 BMF-NSCLC below 3-3.5 cm, with minor neurological symptoms, located in parts of the brain not accessible to surgery, with controlled extracranial disease. Whole brain radiotherapy (WBRT) following SRS reduces the risk of local relapse; in selected patients median survival reaches more than 10 months. Whole brain radiotherapy alone is a treatment in patients with multiple metastases, poor performance status, uncontrolled extracranial disease, disqualified from surgery or SRS with median survival 3 to 6 months. There is no doubt that there are patients with BMF-NSCLC who should receive only the best supportive care. There is a debate in the literature on how to select these patients.

Methods and results of local treatment of brain metastases in patients with breast cancer.

This article presents methods and results of surgical treatment and radiation therapy of brain metastases in breast cancer patients (brain metastases from breast cancer BMF-BC). Based on the literature data, it was shown that patients with single BMF-BC, aged less than 65 years, with Karnofsky score (KPS) of 70 or more and with cured or controlled extracranial disease are the best candidates to surgical treatment. Irrespective of the extracranial disease control status, there are indications for surgery in patients with symptomatic mass effect (tumour diameter larger than 3 cm) and patients with obstructive hydrocephalus from their BMF-BC. Stereotactic radiosurgery (SRS) has some advantages over surgery, with similar effectiveness: it may be used in the treatment of lesions inaccessible to surgery, the number of lesion is not a limiting factor if each lesion is small (< 3) and adequate doses can be delivered, it is not contraindicated in patients with active extracranial disease, it does not interfere with ongoing systemic treatment, and it does not require general anaesthesia or hospitalisation. A disadvantage of SRS, as compared to whole brain radiotherapy (WBRT), in patients with BMF-BC is the possibility of subsequent development of new lesion in the non-irradiated field. Thus the majority of the BMF-BC patients are not good candidates to surgery or SRS; WBRT alone or combined with a systemic treatment still plays a major role in the treatment of these patients.

Correlation between blood and lymphatic vessel density and results of contrast-enhanced spectral mammography.

UNLABELLED: Contrast-enhanced spectral mammography (CESM) is a novel technique used for detection of tumour vascularity by imaging the moment in which contrast, delivered to the lesion by blood vessels, leaks out of them, and flows out through lymphatic vessels. In our study, we included 174 women for whom spectral mammography was performed for diagnostic purposes. The relationship between enhancement in CESM and blood vessel density (BVD), lymphatic vessel density (LVD) or the percentage of fields with at least one lymphatic vessel (distribution of podoplanin-positive vessels - DPV) and other related parameters was assessed in 55 cases. BVD, LVD and DPV were assessed immunohistochemically, applying podoplanin and CD31/CD34 as markers of lymphatic and blood vessels, respectively. The sensitivity (in detection of malignant lesions) of CESM was 100%, while its specificity - 39%. We found a significant positive correlation between the intensity of enhancement in CESM and BVD (p = 0.007, r = 0.357) and a negative correlation between the intensity of enhancement in CESM and DPV (p = 0.003, r = -0.390). Lesions with the highest enhancement in CESM showed a high number of blood vessels and a low number of lymphatics. CONCLUSIONS: 1) CESM is a method characterized by high sensitivity and acceptable specificity; 2) the correlation between CESM results and blood/lymphatic vessel density confirms its utility in detection of tissue angiogenesis and/or lymphangiogenesis.

Salvage brachytherapy in combination with interstitial hyperthermia for locally recurrent prostate carcinoma following external beam radiation therapy: a prospective phase II study.

Optimal treatment for patients with only local prostate cancer recurrence after external beam radiation therapy (EBRT) failure remains unclear. Possible curative treatments are radical prostatectomy, cryosurgery, and brachytherapy. Several single institution series proved that high-dose-rate brachytherapy (HDRBT) and pulsed-dose-rate brachytherapy (PDRBT) are reasonable options for this group of patients with acceptable levels of genitourinary and gastrointestinal toxicity. A standard dose prescription and scheme have not been established yet, and the literature presents a wide range of fractionation protocols. Furthermore, hyperthermia has shown the potential to enhance the efficacy of re-irradiation. Consequently, a prospective trial is urgently needed to attain clear structured prospective data regarding the efficacy of salvage brachytherapy with adjuvant hyperthermia for locally recurrent prostate cancer. The purpose of this report is to introduce a new prospective phase II trial that would meet this need. The primary aim of this prospective phase II study combining Iridium-192 brachytherapy with interstitial hyperthermia (IHT) is to analyze toxicity of the combined treatment; a secondary aim is to define the efficacy (bNED, DFS, OS) of salvage brachytherapy. The dose prescribed to PTV will be 30 Gy in 3 fractions for HDRBT, and 60 Gy in 2 fractions for PDRBT. During IHT, the prostate will be heated to the range of 40-47°C for 60 minutes prior to brachytherapy dose delivery. The protocol plans for treatment of 77 patients.

High-dose-rate brachytherapy as a monotherapy for prostate cancer--Single-institution results of the extreme fractionation regimen.

PURPOSE: We report a single-institution retrospective analysis of the outcomes, disease control, and toxicity of high-dose-rate (HDR) brachytherapy used as the only treatment modality (monotherapy) for localized prostate cancer. METHODS: Between 2006 and 2012, 77 patients with diagnosed prostate cancer were treated with HDR brachytherapy as a monotherapy. The prescribed dose was 45 Gy in three separate implants 21 days apart, with single fraction per implant. Of the 77 patients, 67 (87%) received hormonal therapy. Prostate-specific antigen failure was defined according to Phoenix consensus, as nadir + 2 ng/mL. Toxicity was scored according to Common Terminology Criteria for Adverse Events, version 4.03. RESULTS: The median followup time was 57 months (4.75 years). The 5-year actuarial overall survival was 98.7%, biochemical control 96.7%, local control 96.9%, and metastasis-free survival 98.4%. Younger age at the beginning of brachytherapy predicted the onset of bounce phenomenon. There were no Grade 3 or higher acute toxicities detected, and Grade 2 genitourinary acute toxicity developed in 19 patients (24.6%). There were no Grade 2 gastrointestinal complications. No Grade 4 or 5 late toxicity was detected. There were also no Grade 3 gastrointestinal toxicities detected. One patient (1.3%) underwent transurethral resection of the prostate because of Grade 3 urethral stenosis and urinary retention. A total of 26 patients (33.8%) developed Grade 2 late toxicity. CONCLUSIONS: HDR brachytherapy as monotherapy for localized prostate cancer was feasible, effective, and had acceptable toxicity profile.

Palliative thoracic radiotherapy for patients with advanced non-small cell lung cancer and poor performance status.

OBJECTIVE: The evaluation of efficacy of palliative thoracic radiotherapy (PTR) in patients with advanced non-small cell lung cancer (NSCLC) and to compare it with efficacy of supportive care (SC) alone. MATERIALS AND METHODS: Between 2000 and 2012, 235 patients with advanced NSCLC (IIIB and IV) and Karnofsky Performance Status accounted 40-30, were qualified to PTR. In fact, 125 (53.2%) out of them were treated with PTR, and 110 (46.8%)-with SC alone, in accordance with patients expectations. There were no differences between PTR and SC group with respect to patient and tumor characteristics as well as with respect to the type and incidence of symptoms related to the local growth of NSCLC. In all 125 PTR patients the delivered tumor dose was 20Gy given in five daily fractions over five treatment days. All 110 patients who refused PTR were treated with SC in another hospital (28.2%), in a hospice (21.8%) or by general practitioners at home (50.0%). RESULTS: The 90-day overall survival rate in the group of PTR patients was 20.0%, and in the group of SC patients it was 18.2%. Median survival amounted 58 and 59 days, respectively. The efficacy of PTR and SC, relative to the symptoms associated with the local growth of NSCLC, was comparable. Tolerance of PTR was poor and early toxicity-significant. Moreover 41.6% of irradiated patients received PTR within the last 30 days of their lives and 16.0% of these patients-within the last 15 days prior to death. CONCLUSION: The life expectancy of patients with advanced NSCLC and poor performance status (Karnofsky 40-30), who presenting moderate or severe symptoms related to the local growth of cancer, is measured in days or weeks. The effective method of treatment for these patients is modern supportive care rather than PTR.

Role of irradiation in combined treatment of head and neck paragangliomas at the Centre of Oncology in Krakow between 1970-2005.

AIM OF THE STUDY: Aim of the study is to evaluate the results of postoperative radiotherapy of paragangliomas, prognostic factors and causes of treatment failure. MATERIAL AND METHODS: Forty-four patients (39 females and 5 males) aged 20 to 74 years were treated for paraganglioma between 1970 and 2010 at the Centre of Oncology in Kraków. Patient survival probability was estimated with the Kaplan-Meier method. Log-rank tests and Cox proportional hazard model were used in univariate and multivariate analysis, respectively. RESULTS: The most common locations of paragangliomas were the following: the ear, carotid body and internal jugular vein bulb. Forty (91%) out of them were benign and 4 - malignant. All patients underwent surgery followed by adjuvant radiotherapy. The delivered dose ranged from 50 to 72 Gy, the mean dose was 60 Gy. Five-year overall survival was 84%. Five-year relapse-free survival was 84%, either. The multivariate analysis has shown that the dose in an independent prognostic factor for the overall survival. The univariate analysis has shown significantly higher 5-year overall survival in patients who received a dose of 60 Gy or higher - 92% vs. 70% in patients who received a dose lower than 60 Gy. CONCLUSIONS: Postoperative radiotherapy with doses higher than 60 Gy in patients with paragangliomas is associated with longer overall survival.

Palliative thoracic radiotherapy in non-small cell lung cancer. An analysis of 1250 patients. Palliation of symptoms, tolerance and toxicity.

PURPOSE: To present our experience with short-time, split-course palliative thoracic radiotherapy (PTR) in patients with advanced non-small cell lung cancer (NSCLC) with special regard to palliation of symptoms, tolerance and toxicity of PTR treatment. PATIENTS AND METHODS: Between 1980 and 2005, a group of 1250 patients with locally advanced or metastatic NSCLC was treated with PTR in our Center. All patients presented with moderate or severe symptoms related to local cancer growth. RESULTS: The response rate defined as palliation of NSCLC symptoms after PTR was 54.1% for cough, 68% for haemoptysis, 51.1% for thoracic pain, 38.3% for dyspnoea, 12% for hoarseness, and 8% for dysphagia. Tolerance of PTR, expressed in terms of patient compliance to the treatment, was good in 92% of patients (i.e., 2 series of radiotherapy were given at the planned dose and time). Early treatment toxicity was observed in 4.6% of patients and included pneumonitis in 2.3%, intense nausea and vomiting in 0.6%, lung hemorrhage in 0.6%, and severe oesophagitis in 0.5% of patients. Lhermitte's syndrome and broncho-oesophageal fistula were observed in 0.4% and 0.2%, respectively. Six out of 70 patients who survived longer than 2 years developed chronic pulmonary fibrosis with respiratory insufficiency and one patient presented symptoms of radiation-induced myelopathy. CONCLUSIONS: The analysis of our results and data from the literature show that short-time, split-course PTR is a safe and effective method of palliative treatment in patients with advanced NSCLC.

Thymoma: Results of treatment and role of radiotherapy.

PURPOSE: The aim of this study is to assess results of treatment, factors influencing prognosis with regard to causes of failure and treatment tolerance in patients with thymoma. MATERIAL AND METHODS: Between 1966 and 2006, 63 patients with thymoma had been treated at the Centre of Oncology in Krakow. Patients were treated by means of different treatment modalities: surgery followed by radiotherapy (52%), radiotherapy alone (13%), chemoradiotherapy alone (15%), surgery followed by chemoradiotherapy (5%), surgery alone (5%) and others. RESULTS: The 10-year locoregional recurrence-free survival (LRRFS) was 79%, disease free survival (DFS) was 57% and overall survival (OS) was 57%. Masaoka stage was the only independent prognostic factor for LRRFS. Masaoka stage and method of radiotherapy delivery (higher photon energies), were independent prognostic factors for OS. For DFS, the independent prognostic factors were age, type of treatment (favoured surgery followed by radiotherapy or chemoradiotherapy), Masaoka stage and year of start of treatment. Most common reactions were lung fibrosis in 36% of patients (mainly asymptomatic in most patients), pneumonitis (9%) and oesophagitis (4%). CONCLUSIONS: Surgery combined with radiotherapy and chemoradiotherapy and modern radiotherapy techniques are correlated with improvement of survival in patients with early stage thymoma.

[The effectiveness of postoperative external beam radiotherapy for incompletely resected non-small cell lung cancer]. / Ocena skutecznosci pooperacyjnej teleradioterapii chorych na niedrobnokomórkowego raka pluca po niedoszczetnym zabiegu operacyjnym.

In a retrospective analysis of 150 incompletely resected NSCLC patients treated with adjuvant external beam radiotherapy 32 (21.3%) survived 3 years with no symptoms of disease. Ipsilateral mediastinal/hilar lymph node involvement and macroscopic incomplete surgery were the prognostic factors that unfavourably influenced survival in Cox's proportional hazards model. Postoperative external beam radiotherapy was the efficient adjuvant treatment method in microscopically incompletely resected NSCLC, predominantly with no nodes involvement, but had no benefit in those with macroscopic incomplete surgery.

[The efficacy of adjuvant thoracic radiation therapy in NSCLC patients with ipsilateral mediastinal/hilar lymph nodes involvement (clinical trial)]. / Ocena skutecznosci pooperacyjnej teleradioterapii chorych na NDRP zoperowanych miejscowo doszczetnie z obecnoscia przerzutów w usunietych wezlach chlonnych sródpiersia albo wneki (kontrolowane doswiadczenie kliniczne).

Between 1992 and 1999 at the Oncology Centre in Cracow 138 NSCLC patients after complete resection of the tumour with mediastinal/hilar node involvement were included in the prospective clinical trial. The analysis of the results did not show any improvement of survival in the postoperatively irradiated group. Three-year survival rates with no symptoms of disease in postoperative radiotherapy patients compared to surgery alone group were 30% and 29% respectively. In this study adjuvant radiotherapy significantly improved local recurrence rate from 28% in surgery only group to 9% in postoperatively treated patients.