The systemic treatment of recurrent ovarian cancer revisited.

Treatment approaches for relapsed ovarian cancer have evolved over the past decade from a calendar-based decision tree to a patient-oriented biologically driven algorithm. Nowadays, platinum-based chemotherapy should be offered to all patients with a reasonable chance of responding to this therapy. The treatment-free interval for platinum is only one of many factors affecting patients' eligibility for platinum re-treatment. Bevacizumab increases the response to chemotherapy irrespective of the cytotoxic regimen and can be valuable in patients with an urgent need for symptom relief (e.g. pleural effusion, ascites). For patients with recurrent high-grade ovarian cancer, which responds to platinum-based treatment, maintenance therapy with a poly(ADP-ribose) polymerase inhibitor can be offered, regardless of the BRCA mutation status. Here we review contemporary decision-making processes in the systemic treatment of relapsed ovarian cancer.

Phyllodes tumors of the breast. The treatment results for 340 patients from a single cancer centre.

PURPOSE: The primary treatment of choice for patients with phyllodes tumor of the breast (PTB) is surgery. Two major problems regarding the treatment of such patients remain unclear: what is the appropriate surgical margin and what role is played by adjuvant radiotherapy (ART). METHODS: The study provides a retrospective review of all patients with PTB treated between 1952 and 2013 at a single institute. The histology slides were re-examined based on WHO criteria. The clinical characteristics and therapy outcomes were obtained. The five-year survival with no evidence of disease (NED) was used as the end point. RESULTS: The study population comprised 340 women with PTB. Fifty-five percent of the patients were diagnosed with the benign, 11.8% with borderline and 33.2% with malignant PTB. All the patients received primary treatment with surgery (mastectomy-27.1%, and BCS- 72.9%). Local recurrence (LR) was found in 28 (9.1%) of these patients. Four patients with borderline and 8 with malignant PTB who were treated with BCS and had tumor-free margins < 1 cm received ART. None of these patients had LR and all survived 5 years NED. Of the 340 patients from our group, 294 (86.4%) survived five-years NED. CONCLUSION: The prognosis for benign PTB is excellent and can be cured with surgery alone. A sufficient margin would be 0.1 cm (data from the literature) or 0.2-0.4 cm (our study). We recommend application of ART for such patients but the role of ART in patients with borderline and malignant PTB treated with BCS and with surgical margin < 1 cm remains uncertain.

Recurrent mutations of BRCA1, BRCA2 and PALB2 in the population of breast and ovarian cancer patients in Southern Poland.

BACKGROUND: Mutations in the BRCA1, BRCA2 and PALB2 genes are well-established risk factors for the development of breast and/or ovarian cancer. The frequency and spectrum of mutations in these genes has not yet been examined in the population of Southern Poland. METHODS: We examined the entire coding sequences of the BRCA1 and BRCA2 genes and genotyped a recurrent mutation of the PALB2 gene (c.509_510delGA) in 121 women with familial and/or early-onset breast or ovarian cancer from Southern Poland. RESULTS: A BRCA1 mutation was identified in 11 of 121 patients (9.1 %) and a BRCA2 mutation was identified in 10 of 121 patients (8.3 %). Two founder mutations of BRCA1 accounted for 91 % of all BRCA1 mutation carriers (c.5266dupC was identified in six patients and c.181 T > G was identified in four patients). Three of the seven different BRCA2 mutations were detected in two patients each (c.9371A > T, c.9403delC and c.1310_1313delAAGA). Three mutations have not been previously reported in the Polish population (BRCA1 c.3531delT, BRCA2 c.1310_1313delAAGA and BRCA2 c.9027delT). The recurrent PALB2 mutation c.509_510delGA was identified in two patients (1.7 %). CONCLUSIONS: The standard panel of BRCA1 founder mutations is sufficiently sensitive for the identification of BRCA1 mutation carriers in Southern Poland. The BRCA2 mutations c.9371A > T and c.9403delC as well as the PALB2 mutation c.509_510delGA should be included in the testing panel for this population.

Treatment of Patients with Distant Metastases from Phyllodes Tumor of the Breast.

BACKGROUND: Here, the treatment methods and results of patients with phyllodes tumor of the breast (PT) with distant metastases at a single institution are presented. METHODS: A retrospective analysis was performed on a group of 295 patients with PT treated from 1952 to 2010. RESULTS: Distant metastases developed in 37 (12.5 %) patients; 3/160 (1.9 %) patients had benign PT, 6/36 (16.7 %) were considered borderline, and 28/99 (28.3 %) had malignant PT. Most frequently, the metastases were located in the lungs; 28 (75.7 %), bone 7 (18.9 %), brain 4 (10.8 %), and liver 2 (5.4 %). Metastases occurred on overage 21 months (2-57) after surgery. Patients with lung metastases were generally treated with monochemotherapy or polychemotherapy. In one patient Testosterone and in two patients resection of metastases combined with Doxorubicin were used. Patients with bones or brain metastases were treated with palliative radiotherapy only or combined with Doxorubicin. The mean survival (MS) from diagnosis of distant metastases (DM) was 7 months (2-17). The longest mean survival in patients with bones metastases was 11.8 months, the worst survival was for patients with brain metastases--2.8 months. Hormone therapy appeared to have low efficacy (MS: 2 months) as well as monochemotherapy (MS: 3-5 months). Improved MS was obtained using Doxorubicin (7 months) and Doxorubicin with Cisplatin, Cyclophosphamide, or Ifosfamide (9 months). CONCLUSION: The prognosis of patients with DM from PT is poor. The role of surgery and irradiation of such patients is very limited. There appears to be no role for the use of hormone therapy. This study showed that polychemotherapy with Doxorubicin and Ifosfamide suggest that it might be more effective than once thought.

Distant metastases from invasive lobular breast carcinoma classic type - treatment and prognosis.

INTRODUCTION: Invasive lobular carcinoma (ILC) comprises 4-15% of all malignant neoplasms of the breast. The "classical variant of ILC" (C-ILC) constitutes some 60-80% of this cancer. The main cause of treatment failures is dissemination observed in 8-38% patients The disant metastases (DM) are frequently localized in: bones, gastrointestinal tract, uterus, leptomeninges, and ovaries. The aim of this study was to present the methods and results of the treatment of patients with DM from the classical variant of ILC (C-ILC) at a single institution in Poland. MATERIALS AND METHODS: Between January 1983 and December 2004, 210 women with C-ILC of the breast were primarily treated surgically (mastectomy in 182 (86.7%) patients and breast conserving therapy in 28 (13.3%) patients). Then adjuvant therapy (radiotherapy, chemotherapy, and hormonotherapy) was applied according to presence of clinical indications. RESULTS: The present study focused on a group of 41 patients with a median age of 59 that died with DM from C-ILC during the ten-year follow-up. This failure developed on average 65 months (3-186) after surgery of ILC. The most frequently DM developed: bones (39.1%), GI (small bowell, stomach, colon, rectum) - 31.8%, and reproductive organs (ovary, uterus) - 19.1%. In therapy of DM, different configuration surgery, radiotherapy, and chemo-hormonotherapy were used. The median survival after the diagnosis of DM was connected with localization of distant metastases. CONCLUSION: Patients with classic variant of infiltrate lobular cancer of breast should be regularly follow-up, which could permit early diagnosis of distant metastases and improve treatment results.

Toxicity of concurrent chemoradiotherapy for locally advanced cervical cancer.

AIM OF THE STUDY: The analysis of acute and late toxicity of concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC) based on review of 120 patients treated in Centre of Oncology in Krakow between 2001 and 2007. MATERIALS AND METHODS: Medium age of the patients was 52 years (43-66). Overall, 12 patients (10.0%) were in Stage IB2, 54 (45.0%) in Stage II, 43 (35.8%) in Stage III, and 11 (9.2%) in Stage IVA. Squamous cell carcinoma was present in 114 (95.0%) patients. Well-differentiated (grade 1) tumour was found in 39 (32.5%) patients, moderately differentiated (grade 2) in 41 (34.2%), and poorly differentiated (grade 3) in 40 (33.3%). Karnofsky performance status score was 70 in 72 (60.0%) patients, and 80-90 in 48 (40%). External radiation therapy was delivered with high-energy six to 15 MV photon beams using four-field brick technique. The total dose of 50 Gy was given in 25 fractions within five weeks using standard fractionation. Concurrently with external radiotherapy, six cycles of chemotherapy were administered to all the patients as an intravenous infusion of once-weekly cisplatin 40 mg/m2. On completion of external beam radiotherapy, low-dose rate brachytherapy with tandem and two colpostats was performed to deliver the dose of 40 Gy to point A in two 20 Gy insertions at weekly intervals. RESULTS: Of the 120 patients in the investigated group, 78 (65%) were disease-free for five years. Symptoms of acute treatment-related toxicity grade 3 or 4 (WHO) occurred in 21.6% of patients including leucopoenia in 7.5%. anaemia in 5.0%, nausea and vomiting in 3.3%, diarrhea in 5.0%, and urinary tract infection in 0.8%. Full planned treatment (teleradiotherapy + chemotherapy + brachytherapy) completed 78.3% of the group; full planned radiotherapy without full chemotherapy completed 20% of the patients. Late treatment complications of grade 3 or 4 were observed in two (1.6%) patients (narrowing of large intestine requiring surgery and recto-vaginal fistula). CONCLUSIONS: In patients with LACC treated with CCRT, the most frequent acute toxic effects include: haematological disorders (leucopoenia, anaemia), gastrointestinal disorders (nausea and vomiting, diarrhea), vulvo-vaginal disorders, and urinary tract infection. The most frequent late toxic effects included: rectal bleeding, bowel complications requiring surgery, stenosis or recto-vaginal fistula, and haematuria.

Clinical picture of infiltrating lobular carcinoma of the breast: an analysis of 96 patients.

OBJECTIVE: The aim of this study was to present the clinical picture of infiltrating lobular carcinoma (ILC) of the breast. MATERIALS AND METHODS: A detailed analysis was performed for the group of 96 ILC patients subject to initial surgical treatment in the Krakow Branch of Centre of Oncology between 1983 and 1996. The investigated group was selected out of 2,347 breast cancer patients treated during that period, based on re-examination of histologic specimens of the initial patient group. RESULTS: The following distinctive demographic and clinical features of ILC were found: average age of patients: 59 years (37 - 83); average duration of pathological symptoms: five months; most frequent site of primary tumor: upper outer quadrant (54.2%); primary tumor Stage: I/II0 (64.6%), III0A (35.4%); tumor size in breast: up to five cm (69.8%), larger than five cm (30.2%); no axillary lymph nodes involvement in 51% of patients; multifocality of lesions in 10% of patients; contralateral disease occurrence in eight percent of patients; atypical pattern of distant metastases, e.g. gastrointestinal system, gynaecologic organs, and cerebral meninges. CONCLUSIONS: Based on this analysis as well as on literature reports, it was found that the fundamental differences between ILC and infiltrating ductal carcinoma (IDC) included demographic and clinical features as patient age, primary tumor size at diagnosis, incidence of multifocality and contralateral disease, sites of distant metastases, and histopathological status of axillary lymph nodes.

Radiotherapy for carcinoma of the vagina. Immunocytochemical and cytofluorometric analysis of prognostic factors.

BACKGROUND AND PURPOSE: The aim of this study was to assess the potential prognostic factors in patients with primary invasive vaginal carcinoma (PIVC) treated with radical irradiation. PATIENTS AND METHODS: The analysis was performed on 77 patients with PIVC treated between 1985 and 2005 in the Maria Sklodowska-Curie Memorial Institute of Oncology, Cancer Center in Krakow. A total of 36 patients (46.8 %) survived 5 years with no evidence of disease (NED). The following groups of factors were assessed for potential prognostic value: population-based (age), clinical (Karnofsky Performance Score [KPS], hemoglobin level, primary location of the vaginal lesion, macroscopic type, length of the involved vaginal wall, FIGO stage), microscopic (microscopic type, grade, mitotic index, presence of atypical mitoses, lymphatic vessels invasion, lymphocytes/plasmocytes infiltration, focal necrosis, VAIN-3), immunohistochemical (protein p53 expression, MIB-1 index), cytofluorometric (ploidity, index DI, S-phase fraction, proliferation index SG2M) factors. RESULTS: Significantly better 5-year NED was observed in patients: < 60 years, KPS ≥ 80, FIGO stage I and II, grade G1-2, MIB-1 index < 70, S-phase fraction < 10, and proliferation index < 25. Independent factors for better prognosis in the multivariate Cox analysis were age < 60 years, FIGO stage I or II, and MIB-1 index < 70. CONCLUSION: Independent prognostic factors in the radically irradiated PIVC patients were as follows: age, FIGO stage, MIB-1 index.

Effectiveness of radiotherapy in patients with primary invasive vaginal carcinoma.

INTRODUCTION: The aim of the study was to present an institutional experience in radiation therapy of primary invasive vaginal carcinoma (PIVC) patients treated in the Krakow Branch of Centre of Oncology, with special regard to treatment effectiveness and failure causes. MATERIALS AND METHODS: Between February 1967 and January 2007, 162 PIVC patients were treated with radical radiotherapy in the Krakow Branch of Centre of Oncology, Maria Sklodowska-Curie Memorial Institute. Twenty-seven (16.7%) patients in Stage I(0) were treated with intracavitary brachytherapy alone; for 127 (78.4%) patients in Stage I(0)- IV(0) intracavitary brachytherapy was combined with external radiation therapy; and eight (4.9%) patients in Stage IVA(0) were given only external radiotherapy. RESULTS: In the investigated group of 162 patients, five-year disease-free survival was observed in 46.3% of the cases. Patient age and FIGO Stage of neoplastic disease were independent prognostic factors. Five-year disease-free survival was observed in 64.9% of the patients < 60 years of age and only in 30.7% > or = 60 years of age; and in 62.3% of PIVC patients in Stages I and II(0) as compared to 19.7% of Stages III(0) and IV(0) cases. Among 78 patients who died of PIVC, in 60 (76.9%) cases the cause of death was locoregional failure; in six (7.7%), locoregional failure and distant metastasis; and in 12 (15.4%), distant metastasis. CONCLUSIONS: Radiotherapy is effective treatment for PIVC patients. Age below 60 years and non-advanced neoplastic disease were independent favourable prognostic factors in the investigated group of patients. The primary cause of treatment failure was failure to achieve locoregional disease control.

Vaginal and pelvic recurrences in stage I and II endometrial carcinoma--survival and prognostic factors.

AIM OF THE STUDY: The analysis of prognostic factors and treatment outcomes in 106 patients with Stage I and II endometrial carcinoma (EC) treated between 1980 and 2005 in the Center of Oncology, Maria Sklodowska-Curie Memorial Institute, Kracow, Poland, who developed vaginal or pelvic recurrences. MATERIAL AND METHODS: The median age of patients was 61. Stage IB and IC of EC was diagnosed in 48 (45.3%) patients and Stage IIA and IIB in 58 (54.7%) patients. All patients were treated previously with surgery (TAH-BSO) and postoperative radiotherapy. There were 17 (16%) patients with vaginal vault recurrences, 30 (28.3%) with lower one-third vaginal recurrences, and 59 (55.7%) with pelvic recurrences. Palliative treatment (chemo- or hormonotherapy) or best supportive care only was undertaken in 53 (50.0%) patients. Radical treatment was conducted in 70.6% (12/17) of vault recurrences, 86.7% (26/30) of lower one-third vagina recurrences, and 25.4% (15/59) of pelvic recurrences, with surgery (4 patients), brachytherapy +/- chemotherapy (34 patients), and teleradiotherapy +/- chemotherapy (15 patients). RESULTS: The 5-year overall survival rate in the observed group was 17%. Five-year survival was 23.3% (14/60) for patients with KPS 60-70 vs 8.7% (4/46) with KPS 40-50, 25% (12/48) patients with Stage I EC vs 10.3% (6/58) with Stage II EC, and 34% (16/47) patients with vaginal recurrence vs 3.4% (2/59) with pelvic recurrences. CONCLUSIONS: In the analyzed group of 106 patients with Stage I and II EC, treated previously with surgery and postoperative radiotherapy, 5-year overall survival rate was low; in radically treated patients it was 42.1%, and 13.3% for vaginal and pelvis recurrences, respectively. Univariate analysis showed a statistically significant, unfavorable impact of KPS < 60, Stage II and recurrence pelvic. Cox multivariate analysis demonstrated that the only independent prognostic factor for 5-year overall survival was the site of recurrence.

Prognostic factors in patients with carcinoma of the vulva--our own experience and literature review.

AIM OF THE STUDY: The objective was the analysis of prognostic factors and treatment outcomes of 104 patients with vulvar cancer, treated between 1990 and 2003 in the Center of Oncology, Maria Sklodowska-Curie Memorial Institute, Cracow, Poland. MATERIAL AND METHODS: The median age of patients was 67. Advanced disease (TNM III and IVA) was found in 54 (51.9%) patients and grade 2 and 2 in 50 (48.1%). Inguinal lymph nodes were clinically uni- or bilaterally involved in 40.4% of patients. Fifty-seven (54.8%) patients underwent radical vulvectomy with bilateral inguinal lymphadenectomy and 47 (45.2%) radical vulvectomy only. Cancer differentiation was well in 38 (36.2%) of patients, moderate in 38 (36.2%) and poor in 28 (36.6%). Adjuvant radiotherapy was applied in 30 (28.8%) cases. RESULTS: Five-year overall survival rate was observed in 44.4% of patients. Depending on TNM grade, 5-year OS rates were 61.4% for grade 1, 54.9% for grade 2, 40.1% for grade 3 and 13.3% for IVA. In patients aged < 70, 5-year OS rate was 54.7% compared to 30.5% for those > or = 70. Among patients with G1 cancer differentiation 64.4% survived five years, with G2 39.1% and with G3 24.9%, respectively. CONCLUSION: Univariate analysis revealed a statistically significant, unfavorable impact of age > or = 70, with G3 cancer differentiation, clinically confirmed inguinal lymph node involvement and TNM classification stage on 5-year overall survival. Cox multivariate analysis demonstrated that independent prognostic factors for 5-year survival were the age of the patient, clinical status of inguinal lymph nodes and TNM classification grade.

The efficiency of treatment in patients with uterine-confined endometrial cancer.

AIM: To present our experience regarding the efficiency of treatment in patients with uterine-confined endometrial cancer. PATIENTS AND METHODS: 775 patients with uterine-confined endometrial cancer (UCEC) were treated between July 1985 and June 2000 in the Krakow Branch of Sklodowska Memorial Institute. RESULTS: Among the 775 patients, 5-year disease-free survival was observed in 82.8% patients; 96% patients with low risk of disease recurrence, 93.6% patients with intermediate risk and 78.3% patients with high risk survived five years with no evidence of disease. In the group with a high-risk disease recurrence rate, 5-year disease-free survival was statistically higher among patients treated with adjuvant brachytherapy plus external beam radiotherapy (EBRT) in comparison to patients treated with adjuvant brachytherapy (BRT) alone (82.4% vs 72.1%). CONCLUSIONS: The recommended treatment in patients with high and moderate differentiation of UCEC with FIGO Stage IA is surgery alone. Surgery with adjuvant EBRT in the group of patients with intermediate risk of cancer recurrence allows over 90% of patients to be cured. In the group of patients with a high risk of disease recurrence adjuvant BRT with EBRT is statistically more efficient in comparison to BRT alone.