Marian Reinfuss

Prognostic Evaluation of Proliferative Activity and DNA Content in the Phyllodes Tumor of the Breast: Immunohistochemical and Flow Cytometric Study of 118 Cases

The goal of this study was the prognostic evaluation of histology, mitotic rate, S-phase fraction (SPF) and expression of proliferative antigen Ki67 and p53 protein in phyllodes tumor of the breast. The study was performed in the group of 118 patients with phyllodes tumor treated by surgery from 1952 to 1998. Mitotic rate was assessed on the representative histological specimens. Expressions of Ki67 and p53 were evaluated by immunohistochemistry on a section from the corresponding paraffin blocks which were also used for flow cytometric DNA evaluation. Histologically, 52 tumors were benign (LGM), 24 borderline malignancies (BM) while among 42 malignant tumors, 20 were monomorphous (HGM) and the remaining 22 revealed heterologic elements (HGH). Tumor recurrencies occurred in 17 patients, predominantly during the first three years after surgery, and 13 patients died of the tumor (1 BM, 12 both malignant variants). Multivariate analysis demonstrated mitotic rate, SPF and p53 expression as independent prognostic parameters for the disease-free survival. Histological tumor type and expression of Ki67 influenced independently the overall survival. In conclusion, the histological type of tumor phyllodes forms the basis for the prognosis of clinical outcome, but the indicators of the proliferative activity, especially Ki67 index, are valuable prognostic factors among patients with malignant variant of phyllodes tumor of the breast. Expression of the p53 protein in tumor cells could be also useful when the percentage of cells and intensity of expression are considered.

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.

Malignant Phyllodes Tumor of the Breast: Treatment and Prognosis

Surgery remains the mainstay of the treatment in patients with malignant phyllodes tumor of the breast (MPTB); however, the extent of surgery (breast conserving surgery [BCS] versus mastectomy) and the role of adjuvant radiotherapy have been controversial. We report a single institutions experience with MPTB. We discuss controversial therapeutic aspects of this rare tumor. Seventy patients with MPTB treated primarily with surgery were evaluated. The mean age was 50 years (21–76), and the mean size of the tumor was 6 cm. Thirty‐four (48.6%) patients were treated with total mastectomy, and 36 (51.4%) were treated with BCS (lumpectomy or wide local excision). Microscopic surgical margins were free of tumor in all cases. In 64 (91.4%) patients, margins were ≥1 cm. Remaining 6 (8.6%) patients treated with BCS margins were <1 cm and subsequently radiotherapy was performed. Among 70 patients, 58 (82.9%) had no evidence of disease (NED) after 5 years. The extent of surgery was not significantly related to the 5‐year NED survival rates (82.4% in patients who underwent mastectomy and 83.3% in patients who underwent BCS only or BCS with adjuvant irradiation). The 5‐year NED survival rates in BCS (tumor‐free margin ≥1 cm) and BCS with irradiation (tumor‐free margin <1 cm) groups were identical (83.3%). Our data support the potential use of BCS in patients with MPTB. Mastectomy is indicated only if tumor‐free margins cannot be obtained by BCS. Adjuvant radiotherapy may be considered if tumor‐free margins are <1 cm.

Radiotherapy facilities, equipment, and staffing in Poland: 2005–2011

BACKGROUND AND PURPOSE To evaluate the current status of radiotherapy facilities, staffing, and equipment, treatment and patients in Poland for the years 2005-2011 following implementation of the National Cancer Programme. METHODS A survey was sent to the radiotherapy centres in Poland to collect data on available equipment, staffing, and treatments in the years 2005-2011. RESULTS In 2011, 76,000 patients were treated with radiotherapy at 32 centres vs. 63,000 patients at 23 centres in 2005. Number of patients increased by 21%. In 2011, there were 453 radiation oncologists - specialists (1 in 168 patients), 325 medical physicists (1 in 215 patients), and 883 radiotherapy technicians (1 in 86 patients) vs. 320, 188, and 652, respectively, in 2005. The number of linear accelerators increased by 60%, from 70 units in 2005 to 112 in 2011. The current linac/patient ratio in Poland is 1 linac per 678 patients. Waiting times from diagnosis to the start of treatment has decreased. CONCLUSION Compared to 2005, there are more treatment facilities, more and better equipment (linacs), and more cancer care specialists. There are still large differences between the 16 Polish provinces in terms of equipment availability and ease of access to treatment. However, radiotherapy services in Poland have improved dramatically since the year 2005.

The Efficiency and Tolerance of Half-Body Irradiation (HBI) in Patients with Multiple Metastases

Aim To present our experience regarding the efficiency and tolerance of half-body irradiation in patients with multiple cancer metastases. Patients and Methods: Between January 1986 and December 1997, 102 patients with multiple cancer metastases received half-body irradiation (HBI) at the Center of Oncology – Maria Sklodowska-Curie Memorial Institute in Krakow. Most of the patients (93/102) had bone metastases (Table 1). The HBI was performed with 9 MV photon beam from linear accelerator. In 88 patients only one region (upper, mid or lower) was treated, and 14 patients received upper and lower HBI (13 patients), or upper and mid HBI (one patient) (Table 2). The mean doses were: 6 Gy in upper HBI, 8 Gy in mid HBI, and 9 Gy in lower HBI (Table 3). Results: The positive palliative effect (complete or partial pain relief) was observed in 77 (75.5%) patients (Table 4). Complete pain relief was higher in patients with prostate cancer, and in patients who received mid or lower HBI. During follow-up 47 (46.1%) patients developed pain progression after treatment (Table 5). The probability of survival without pain progression was higher in patients who developed complete pain relief (86.7% at 6 months, 69.3% at 12 and 24 months) than in patients with partial response (52.9% at 6 months, 32.8% at 12 months, and 5.5% at 12 and 24 months) (Figure 1). In most of the patients (74/102, 72.5%) the tolerance was good. Conclusions: HBI is an efficient method for palliation in patients with multiple painful metastases.Ziel Darstellung unserer Erfahrungen hinsichtlich Wirksamkeit und Verträglichkeit der Halbkörperbestrahlung bei Patienten mit multiplen Tumormetastasen. Patienten und Methodik: Zwischen Januar 1986 und Dezember 1997 erhielten 102 Patienten mit multiplen Metastasen am Onkologie-Zentrum des Maria-Sklodowska-Curie-Memorial-Institutes in Krakau eine Halbkörperbestrahlung. Die meisten Patienten (93/102) hatten Knochenmetastasen (Tabelle 1). Die Halbkörperbestrahlung wurde mit 9-MV-Photonen eines Linearbeschleunigers durchgeführt. Bei 88 Patienten wurde nur eine Region (obere, mittlere oder untere) bestrahlt; 14 Patienten erhielten eine obere und untere Halbkörperbestrahlung (n = 13) oder obere und mittlere Halbkörperbestrahlung (n = 1) (Tabelle 2). Die Dosis betrug im Mittel 6 Gy bei oberer Halbkörperbestrahlung, 8 Gy bei mittlerer und 9 Gy bei unterer Halbkörperbestrahlung (Tabelle 3). Ergebnisse: Eine gute Palliation (vollständige oder teilweise Schmerzlinderung) wurde bei 77 Patienten (75,5%) beobachtet (Tabelle 4). Zu kompletter Schmerzlinderung kam es häufiger bei Prostatakarzinompatienten und bei Patienten, die mittlere oder untere Halbkörperbestrahlung erhalten hatten. Im weiteren Verlauf kam es bei 47 Patienten (46,1%) zur Schmerzprogression (Tabelle 5). Die Wahrscheinlichkeit, ohne Schmerzprogression zu überleben, war bei Patienten mit kompletter Schmerzlinderung höher (86,7% nach 6 Monaten, 69,3% nach 12 und 24 Monaten) als bei Patienten mit partiellem Ansprechen (52,9% nach 6 Monaten, 32,8% nach 12 und 5,5% nach 24 Monaten) (Abbildung 1). Die Verträglichkeit war bei den meisten Patienten gut (74/102; 72,5%). Schlussfolgerung: Die Halbkörperbestrahlung ist eine wirksame Palliativmethode für Patienten mit multiplen schmerzhaften Metastasen.

Hematogenous Metastases in Patients with Stage I or II Endometrial Carcinoma

AimsThe aim of this study was to present the characteristics, methods of treatment, and the survival of patients with hematogenous metastases from endometrial carcinoma, free from local and other distant recurrences.Patients and MethodsIn 1,610 endometrial carcinoma patients managed with surgery and postoperative radiotherapy, we defined hematogenous metastases as a tumor spread to the lung or other sites via hematogenous routes.ResultsA total of 110 patients with stage I and II endometrial carcinoma, presenting with 134 metastases sites (69 in the lungs, 32 in the liver, 23 in the bones, and 10 in the brain), were observed. Progestin and combination chemotherapy were the most commonly used therapies. Primary treatment consisted of surgery in patients with solitary metastases to the lung (30 patients), liver (2 patients), and brain (2 patients). Radiotherapy was performed in 32 patients with metastases to the brain and bones. Presenting with a 36-month survival rate were 11.6% (8/69) of patients with metastases to the lungs, 6.3% (2/32) of patients with metastases to the liver, 8.7% (2/23) of patients with metastases to the bones, and 20.0% (2/10) of patients with metastases to the brain.ConclusionsHormonal therapy and chemotherapy play a major role in the palliative management of patients with hematogenous metastases from endometrial carcinoma to the liver, lungs, and bones. Radical treatment in patients with metastases to the lung or liver consists of resection of the metastasis combined with chemo- and/or hormonotherapy for metastases to the bones treatment consists of radiotherapy + chemotherapy, for metastasis to the brain treatment consists of resection combined with radiotherapy.ZusammenfassungZielDarstellung von Charakteristika, Behandlungsmethoden und Überleben von Patientinnen mit hämatogenen Metastasen des Endometriumkarzinoms ohne lokalen und Fernrezidive.Patienten und MethodenBei 1610 Patientinnen mit Endometriumkarzinom, die mit Operation und postoperativer Strahlentherapie behandelt worden waren, definierten wir hämatogene Metastasen als Ausbreitung bösartiger Tumoren in die Lungen oder andere Regionen über die Blutbahn.ErgebnisseWir beobachteten 110 Endometriumkarzinom-Patientinnen, Stadien I und II, bei denen 134 Metastasenlokalisatione festgestellt wurden: 69 in den Lungen, 32 in der Leber, 23 in den Knochen und 10 im Gehirn. Die am häufigsten eingesetzten Behandlungsregime waren Progestine und Kombinationschemotherapie. Erstbehandlung waren Operationen bei Patientinnen mit einzelnen Lungenmetastasen (30 Fälle), Lebermetastasen (2 Fälle) und Gehirnmetastasen (2 Fälle). Eine Strahlentherapie wurde bei 32 Patienten mit Gehirnmetastasen und mit Knochenmetastasen durchgeführt. Nach 36 Monaten betrug die Überlebensrate 11,6% (8/69) der Patientinnen mit Lungenmetastasen, 6,3% (2/32) der Patientinnen mit Lebermetastasen, 8,7% (2/23) der Patientinnen mit Knochenmetastasen und 20,0% (2/10) der Patientinnen mit Gehirnmetastasen.SchlussfolgerungHormon- und Chemotherapie spielen eine wesentliche Rolle in der palliativen Behandlung von Patientinnen mit hämatogenen Leber-, Lungen- und Knochenmetastasen des Endometriumkarzinoms. Die radikale Behandlung bei Lungen- oder Lebermetastasen umfasst chirurgische Metastasenresektion und adjuvante Chemo- und/oder Hormontherapie, bei Knochenmetastasen Strahlen- plus Chemotherapie und bei Gehirnmetastasen chirurgische Metastasenresektion und adjuvante Strahlentherapie.

Changes in the clinical characteristics, treatment options, and therapy outcomes in patients with phyllodes tumor of the breast during 55 years of experience

Background Data from the literature suggests that the clinical picture of phyllodes tumor (PT) of the breast, as well as treatment options and perhaps therapy outcomes, have significantly changed. The aim of this work was to review these changes by analysis of consecutive patients with PT over a 55-year period at a single institution. Material/Methods From 1952 to 2007, 280 women with PT were treated surgically at the Maria Skłodowska-Curie Memorial Institute of Oncology, Cancer Center in Cracow. Age, size of breast tumor, microscopic type, extent of surgery, and therapy outcomes were compared between 2 groups: 190 patients treated from 1952 to 1991 vs 90 patients treated from 1992 to 2007. Results The results show that the 1992–2007 group compared to the 1952–1991 included more patients <50 years of age, with tumor <5 cm in diameter, undergoing breast-conserving therapy, as well as no evidence of disease at 5-year survival had increased and this change was statistically significant. In addition, malignant PT cases had decreased in frequency. Conclusions The results of this study show that patients with PT are increasingly younger, the breast tumors at diagnosis are smaller, malignant PT is becoming less frequent, and BCT is now the treatment of choice. Most importantly, the general treatment outcomes are significantly better.

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.