Tomasz Walasek

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. Lhermittes 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.

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 patients 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.

Multimodality treatment of noninflammatory stage IIIb breast cancer

The 1990s have established the contribution of multimodality therapy in the management of IIIb noninflammatory breast cancer (IIIb NIBC), by reducing the odds of recurrence and death.

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.

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.

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.

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.

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.

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.

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.