Michał Spych

Long-term survival of endometrioid endometrial cancer patients

Introduction To establish risk factors for onset and progression of endometrioid endometrial cancer still remains the aim of scientists. The aim of the study was to determine disease-free survival (DFS) and overall survival (OS) in women with endometrioid endometrial cancer. Material and methods A retrospective review of 142 patients with endometrioid endometrial cancer after surgery treated with adjuvant radiotherapy and/or chemotherapy in the Regional Cancer Centre in Lodz between 2002 and 2004 was performed. Clinical and pathological data were correlated with clinical outcome and survival. Results In 3 patients (2.1%) clinical progression was diagnosed during the treatment. In 23 patients (16.7%) after primary remission, relapse was diagnosed 2-56 months after treatment. DFS and OS were 81.7% and 83.1% respectively. Better DFS significantly correlated with larger number of pregnancies (> 1), stage I of the disease and optimal surgery. Lower stage of disease, pelvic lymph node dissection, optimal surgery and depth of myometrial infiltration ≤ 50% were independent prognostic factors for better OS. Conclusions The results of our study provided significant evidence that early detection of endometrioid endometrial cancer enables optimal surgery. It reduces the indications for adjuvant therapy in stage I of the disease, and makes the prognosis significantly better. Other clinical and pathological factors such as numerous pregnancies, pelvic lymphadenectomy, and depth of myometrial infiltration, although important, are of less significance. Further prospective, randomized studies are necessary to prove the role of these factors.

The AgNORs count in predicting long-term survival in serous ovarian cancer.

Introduction The value of argyrophilic nucleolar organizer regions (AgNORs) to predict survival in patients with ovarian cancer has not been clearly explained yet. The aim of study was to assess the value of analysis of the mean number of AgNORs per nucleus (mAgNOR) and mean percentage of nuclei with five or more AgNORs per nucleus (pAgNOR) in the prediction of disease-free survival (DFS) and overall survival (OS) in patients with serous ovarian cancer. Material and methods The study examined 52 patients treated for serous ovarian cancer with a follow-up period of 2-143 months. After silver staining paraffin specimens from primary surgery, mAgNOR and pAgNOR in cancer cells were counted and analyzed. Age, grading, radicality of surgery and FIGO staging were analyzed as covariates. Results Mean mAgNOR equaled 4.4 ±0.9 and pAgNOR equaled 42.2 ±20.8%. Both mAgNOR and pAgNOR were the lowest in G1 tumors. The mAgNOR and pAgNOR were lower in stage I than stage IV cancers. The DFS and OS rates were respectively 15.4% and 21.2%. In univariate analysis FIGO staging, grading, and pAgNOR were associated with worse prognosis, while radicality of surgery remained a significant protective factor in terms of DFS. Higher FIGO staging and older age worsened OS. In multivariate analysis FIGO staging remained significantly associated with both DFS (HR 1.98; 95% CI 1.05-3.71) and OS (HR 1.76; 95% CI 1.00-3.10), while age affected OS rates (HR 1.78; 95% CI 1.04-2.95). Conclusions mAgNOR and pAgNOR are useful markers of cellular kinetics. Prospective studies in larger populations are needed to confirm these results in terms of AgNORs’ effects on survival.

The analysis of prognostic factors affecting post-radiation acute reaction after conformal radiotherapy for non-small cell lung cancer.

Introduction The aim was to evaluate the risk of acute side effects in the lung after 3-dimensional conformal radiotherapy (3D-CRT) in patients treated for non-small cell lung cancer (NSCLC). An attempt was made to single out clinical factors and factors related to treatment technique which may induce acute post-radiation pneumonitis. Material and methods The analysis concerned 34 consecutive patients who underwent radical radiation therapy for NSCLC. Intensity of early toxicity was evaluated using modified RTOG/EORTC toxicity score. The endpoint for this analysis was the occurrence of radiation pneumonitis of grade 2 or higher. Factors related to treatment techniques were included in the statistical analysis. Results Fifty-three percent of patients included in the study suffered from acute post-radiation pneumonitis. The results of the study revealed the existence of lung tissue sensitivity to low doses of ionizing radiation. The multivariate analysis showed that total lung volume receiving a low dose of 10 Gy increased the risk of post-radiation pneumonitis (p = 0.01). Conclusions Acute post-radiation pneumonitis was a relevant clinical problem in patients who underwent radical radiotherapy for non-small cell lung cancer. The lung volume receiving a dose of 10 Gy was the most important dosimetric factor which influenced the post-radiation acute pneumonitis.

Bone metastases from gynaecological epithelial cancers

The aim of this study was to investigate the clinical features and prognosis in patients with gynaecological epithelial cancers metastasised to bones. A total of 26 patients were studied retrospectively. Clinical and pathological data were analysed along with a follow-up. It was found that the interval from primary diagnosis of cancer until bony relapse varied between 0 and 163 months (31.4 ± 36.8). Bone metastases were solitary in 11 cases and multifocal in 15 cases. A total of 14 patients demonstrated only bony metastases while 12 had both bony and non-bony metastases. The time to follow-up from the diagnosis of osseous relapse varied between 1 and 43 months (10.0 ± 10.4). During follow-ups, 13 patients died and 13 patients survived. In both univariate and multivariate analyses, synchronous non-bony metastases and symptomatic treatment without oncological therapy impaired prognosis. It was concluded that even in the presence of multiple bone metastases, some patients may benefit from radiotherapy, chemotherapy or a combination of both, rather than palliative care alone, providing they do not have additional soft tissue metastases.

Isolated metastasis to the foot as an extremely rare presenting feature of primary endometrial cancer.

Endometrial cancer is the most common invasive cancer of the female genital tract, with an increasing incidence rate. Abnormal uterine bleeding is the presenting symptom in 75-90% of cases [1, 2]. The majority of patients with endometrial cancer are diagnosed with no evidence of extra-uterine spread (70-80% stage I), which gives patients better prognosis [1, 3]. In more advanced disease the sites commonly affected outside the uterus are pelvic and para-aortic lymph nodes and the ovaries [4]. Similarly to uterine sarcomas, distant metastases in advanced or recurrent endometrial cancer most commonly involve the lungs, liver, central nervous system and skin [4–6]. Metastases to bones have been described in 2-15% of patients with metastatic disease, and the most common site of osseous metastases are vertebrae, with pelvic bones, ribs and sternum [3, 7]. Isolated metastases to bone extremities are extremely rare, and thought to result from the haematological spread of cancer cells [5]. The review of the Medline database by searching the items endometrial cancer and metastases to extremities showed twenty such cases, with only nine cases when metastatic tumour of the foot was the first manifestation of endometrial cancer (Table I) [3, 5, 7–13]. Table I Isolated metastasis to the bones of the extremities as the first manifestation of endometrial cancer – review of the literature A 74-year-old female suffered from pain and swelling of the right foot from October 2006. In the X-ray picture and bone scintigraphy, suspected lesion of the right calcaneus, talus and metatarsal bones was detected (Figure 1). Afterwards it was histologically verified in the biopsy as metastatic cancer (Figure 2). The patient had no vaginal bleeding or other gynaecological symptoms, but subsequent computed tomography scans showed an enlarged uterus. Uterine curettage confirmed the diagnosis of endometrial cancer. The patient was treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy without pelvic lymph node dissection in December 2006. The histological diagnosis was a moderate differentiated (G2) endometrioid endometrial cancer invading the outer half of the myometrium (> 1/2) with invasion of cervical stroma. The fallopian tubes and the ovaries showed no signs of metastases. No evidence of macroscopic abdominopelvic metastases was found at surgery. Her disease was classified as clinical stage IVB according to FIGO 2009 staging, but in the TNM classification it was pT2 Nx M2. Figure 1 Radiograph of the right foot demonstrating metastases of the endometrial cancer Figure 2 Metastatic endometrial cancer cells in the fine needle aspiration of the tumour of the foot (H + E, 200× magnification) In January 2007 the patient was admitted to the department of palliative radiotherapy. She received irradiation by Co 60 until a total dose of 20 Gy to the tumour of the right foot, with complete resolution of symptoms. The patient was discharged from hospital in March 2007. During the observation from surgery in December 2006 until June 2010 no other metastases were detected. The patient remains alive and asymptomatic 43 months after the diagnosis of metastatic endometrial cancer to the foot. Our report presented in the previous section has three main peculiar features: 1) it demonstrates endometrial cancer that presented with osseous metastasis, which is a rare occurrence, 2) the metastatic tumour was located in the foot, which is extremely rare, 3) the bone lesion was a single bone metastasis, which is unusual in such cases. Additionally, the case in which isolated metastatic tumour of the extremity was the first manifestation of endometrial cancer is the tenth such case reported in the literature (Table I), and the second one located in the calcaneus and involving talus and metatarsal bones [8]. Despite the rarity of metastases to the upper and lower extremities, there is a need to have a high index of suspicion for metastasis in patients with a history of endometrial cancer who present with swelling or bony tenderness. The initial diagnosis can be challenging, as the symptoms of pain and swelling are often attributed to other more common benign conditions such as soft tissue inflammation, trauma, arthritis, and osteomyelitis [7]. It is important to consider bone metastasis as a possible diagnosis also in patients without history of cancer, but with osseous pain not responding to conservative treatment [5, 9–13]. Appropriate imaging may include plain X-ray picture and radionuclide bone scans [3]. Technetium diphosphonate bone scans can be positive up to 18 months before a lesion is detectable on plain X-ray [14]. Therefore, a biopsy should be performed in patients with suspected lesions, and who demonstrate evidence of bony destruction [4]. The treatment strategy in patients with confirmed isolated metastatic lesion in the bone extremity still remains a topic of controversy, because of the few descriptions available in the literature and the different bone sites involved. For these reasons, a common suitable treatment regimen cannot be established and treatment should be tailor suited to each patient. The treatment of irradiation with or without surgery, hormone therapy and chemotherapy is reported as effective in most cases and may be curative [4, 5, 7, 9, 11, 12]. The main goal of treatment should be to eliminate or palliate pain and prolong survival.

Assessment of the argyrophilic nucleolar organizer region area/nucleus ratio in ovarian serous epithelial adenomas, borderline tumors and cancers.

Introduction There is a need to assess the value of the novel potentially useful biomarkers in ovarian tumors. The aim of study was to assess the value of sAgNOR analysis in ovarian serous epithelial tumors. Material and methods The analysis was performed in ovaries from 113 patients treated operatively due to serous ovarian tumors (30 adenomas, 14 borderline tumors and 69 cancers). After silver staining of paraffin specimens from surgery, sAgNOR in tumor cells was analyzed. Additionally, the value of the argyrophilic nucleolar organizer region area/nucleus ratio (sAgNOR) in the prediction of disease-free survival (DFS) and overall survival (OS) in 52 patients with serous ovarian cancer with complete follow-ups in November 2009 was evaluated. Age, grading, radicality of surgery and FIGO staging were analyzed as additional factors. Results sAgNOR in adenomas, borderline tumors and cancers was in the following ranges: (0.73 ±0.23) × 106, (0.81 ±0.18) × 106 and (0.96 ±0.33) × 106 [AgNOR/cm2] respectively. In cancers from G1 to G3 sAgNOR was (1.02 ±0.32) × 106 (G1), (0.98 ±0.37) × 106 (G2) and (0.82 ±0.24) × 106 (G3) [AgNOR/cm2] respectively. In univariate analysis, but not in multivariate analysis, staging negatively correlated with better DFS and OS. sAgNOR, age of patients, grading and radicality of surgery were not associated with DFS or OS in either univariate or multivariate analysis. Conclusions sAgNOR analysis is not sufficient to precisely characterize cellular kinetics in serous ovarian tumors, and the analysis of sAgNOR, mAgNOR and pAgNOR should be performed commonly. The prognostic significance of sAgNOR in patients with serous ovarian cancer was not proven.

Construction of a tissue microarray with two millimeters cores of endometrioid endometrial cancer: factors affecting the quality of the recipient block

The tissue microarray (TMA) method currently is not used to render a primary diagnosis of cancer, but its scientific value has been proved in studies of various cancer types. TMA technology still is not used often for uterine tumors, however. We investigated the repeatability of histological diagnosis of endometrioid endometrial cancer (EEC) using conventional histology and TMA using 2 mm cores. We examined EEC tissues from 171 patients. Formalin fixed, paraffin embedded tissue donor blocks from EEC specimens were selected and examined histologically. Duplicate 2 mm tissue cores were inserted into a TMA recipient block. EEC tissues were examined as hematoxylin-eosin stained sections from the TMAs. EEC tissue was identified in the TMAs in 158 cases (92.4%) and not found in 13 cases (7.6%). On the TMA slides, both EEC positive cores were identified in 129 cases (75.4%), but only one core in 29 cases (17.0%). Among 342 biopsies of the donor blocks (each case in duplicate), EEC was found in 287 cases (83.9%) using the TMA: 124/146 (84.9%) with superficial infiltration, 153/178 (86.0%) with deep myometrial infiltration, and 10/18 (55.6%) without myometrial infiltration. We concluded that two 2 mm tissue cores from a biopsy of a donor block inserted into a TMA recipient block were sufficient to diagnose EEC in more than 90% of cases. EEC was identified in the TMAs with similar frequency with respect to superficial and deep myometrial infiltration. Cases without myometrial infiltration were identified less often.

Solitary brain metastasis of an occult and stable small-cell lung cancer in a schizophrenic patient: a 3-year control.

Small-cell lung cancer is a highly aggressive carcinoma, with poorer prognosis in patients with brain metastases. We present the case of a 49-year-old woman diagnosed with a cerebellar tumour which, following surgery, was revealed to be a metastatic small-cell lung carcinoma. Subsequent CT and PET scanning showed a small, isolated 8 mm nodule in the upper lobe of the right lung. The patient was suffering from schizophrenia and has been treated with clozapine for 17 years. Because of the unusual presentation, there was no therapy given for the primary tumour at the time, and systemic therapy or surgery was discussed. However, 18 months later, the nodule was slightly larger (14 mm), and surgery was performed. On pathology examination, the tumour was presented as a typical small-cell carcinoma. Standard chest irradiation with systemic chemotherapy was given. At the time of writing, 39 months after diagnosis of metastatic small-cell carcinoma, the patient is disease free. However, this case is unusual in that a long-term observation of a small stable primary tumour in the lung took place without any therapy being given. This case strongly supports the thesis that small-cell lung cancer may comprise a heterogeneous group of tumours with different biological properties. The proapoptotic effect of clozapine may be also taken into account.

Central nervous system metastases from epithelial ovarian cancer

The aim of the study was to assess the clinical features and prognosis in patients with epithelial ovarian cancer (EOC) metastasised to the central nervous system (CNS). A total of 15 patients were studied retrospectively. Clinical and pathological data and follow-up were analysed. It was found that at the diagnosis of primary EOC, the patients were 41–69 years old (56.6 ± 8.3). The interval from diagnosis of primary EOC until the relapse was 2–39 months (19.1 ± 10.5). Palliative radiotherapy was the treatment of the CNS relapse in 13 patients (86.7%). The follow-up after CNS relapse varied 0.5–15 months (4.7 ± 4.2). At the time of retrospective analysis, none of the patients were still alive. Multifocality of the CNS metastases, the presence of synchronous extracranial metastases and locations in the brain were not associated with survival. It was concluded that the development of the CNS metastases seems to be not uncommon in patients with advanced ovarian cancer. Despite oncological treatment, they are indicators of poor prognosis, and most of the patients do not survive beyond the first year of follow-up.

Availability and outcomes of radiotherapy in Central Poland during the 2005-2012 period - an observational study

BackgroundUsing a cross-database integrative approach, we performed an epidemiological analysis in a representative region of central Poland to evaluate the availability of radiotherapy (RTx) and overall survival of adult patients undergoing RTx for cancer.MethodsEpidemiological data on cancer incidence in the 2005–2012 period were obtained from the Nationwide Cancer Registry. Using data from the Ministry of Internal Affairs, we collected survival information of all patients treated in the only centre providing RTx for a region inhabited by approximately 2.6 million people.ResultsAfter filtering out individuals on the basis of exclusion criteria, the final dataset covered 17,736 patients. Availability of RTx increased marginally, from 23.5% (2005) to 24.4% (2011, R = 0.39, p = 0.38), with the highest values noted in patients with cervical (78.5%), prostate (70.6%) and breast cancer (62.7%). However, due to the decreasing population of the region, we noted increasing disparity in the likelihood of receiving RTx depending on the patient’s area of residence, with rural areas becoming progressively more neglected. The best prognosis was noted among patients with breast or prostate cancer with 5-year OS rates reaching 81.2% and 83.3%, respectively. Multivariate analysis controlling for type of diagnosis and patient age showed a time-dependent improvement in outcomes (HR(95% CI): 0.96(0.94-0.98); p < 0.0001).ConclusionsAvailability of RTx in Poland is still below that reported by developed European centres. Survival of patients undergoing radical RTx has gradually improved, although it is still below that of leading RTx departments, potentially due to delayed diagnosis or organisational barriers, necessitating further investigations.