Randomized Phase III Study Comparing Neoadjuvant Chemotherapy Followed by Surgery Versus Chemoradiation in Stage IB2-IIB Cervical Cancer: EORTC-55994.

PURPOSE: This multicenter trial by the European Organisation for Research and Treatment of Cancer Gynecological Cancer Group was motivated by conflicting evidence on the value of neoadjuvant chemotherapy before surgery compared with concomitant chemoradiotherapy (CCRT) in stage IB2-IIB cervical carcinoma. METHODS: Between May 2002 and January 2014, 626 patients with International Federation of Gynecology and Obstetrics stage IB2-IIb were randomly assigned between neoadjuvant chemotherapy followed by surgery (NACT-S; n = 314) and standard CCRT (n = 312). The primary end point was 5-year overall survival (OS) rate. Secondary end points were progression-free survival, OS, toxicity, and health-related quality of life (HRQOL). RESULTS: After a median follow-up of 8.7 years, 198 patients (31.6%) died. Age, stage, and cell type were balanced in both arms. Protocol treatment was completed in 223 of 314 (71%) patients in NACT-S and 257 of 312(82%) in CCRT arms. Main reasons for incomplete protocol treatment were toxicity (30 of 314; 9.6%) and progressive disease (21 of 314; 6.7%) in the NACT-S arm and toxicity (23 of 312; 7.4%) and patient refusal (13 of 312; 4.2%) in the CCRT arm. Additional radiotherapy after completed NACT-S was given to 107 patients (48%), and additional surgery to 20 patients (8%) after completed CCRT. Short-term adverse events (AEs) ≥grade 3 occurred more frequently with NACT-S (41% v 23%), and long-term AEs ≥grade 3 more often with CCRT (21% v 15%). The 5-year OS was not significantly different between NACT-S (72%; 95% CI, 66 to 77) and CCRT (76%; 95% CI, 70 to 80). CONCLUSION: This trial failed to demonstrate superiority in favor of the NACT-S arm but resulted in acceptable morbidity and HRQOL in both arms.

[Micrometastases in sentinel lymph node in endometrial cancer patients]. / Mikroprzerzuty w wartowniczym wezle chlonnym u chorych na raka endometrium.

BACKGROUND: Detection of micrometastases in sentinel lymph nodes (SLN) extends our knowledge of lymphatic spread in endometrial cancer, although its clinical significance has not yet been confirmed. OBJECTIVES: The aim of study was to determine the incidence of SLN micrometastases and to analyze the association between micrometastases and disease relapse. MATERIAL AND METHODS: Fifty-four patients with endometrioid endometrial cancer underwent routine surgical therapy and sentinel lymph node biopsy (SLNB). SLNB was performed using two techniques: cervical injection of 99mTc-labelled albumin or blue dye and fundal injection of blue dye. SLNs were subjected to ultrastaging with immunohistochemistry (AE1/AE3, 150µm). RESULTS: At least one SLN was detected in 51 patients (94.4%) and bilateral SLN detection was achieved in 80.4%. Nodal macrometastases were found in 3 patients (6.3%). SLNB enabled us to detect nodal macrometastases in 2 out of those 3 patients. In the third case, detection of SLN micrometastasis allowed to correctly determine the nodal status, thus avoiding the false negative result of SLNB. In 48 patients with detected 184 SLNs, there were 4 patients (8.3%) with micrometastases and 4 (8.3%) with ITC foci. No significant associations between the presence of risk factors (grade, myometrial invasion, cervical invasion, lymphovascular space invasion) and incidence of micrometastases and/or ITC foci in SLNs were found. CONCLUSIONS: Detection of micrometastases may result in lower false-negative rate, thus increasing SLNB safety.

[Chemosensitivity testing in ovarian cancer--prospects for the future]. / Metody okreslajace chemiowrazliwosc komórek raka jajnika in vitro--perspektywy na przyszlosc.

Individualization of treatment on the basis of in vitro chemosensitivity testing constitutes one of the aims of contemporary oncology Although previous studies report advantages resulting from chemosensitivity laboratory tests, the issue remains an area of interest. The aim of this study was to discuss chemosensitivity assay methods of ovarian cancer cells. ATP-TCA (ATP-based tumor chemosensitivity assay) is the most investigated chemosensitivity test in ovarian cancer with well-documented efficacy Potentially it is possible to use the xCELLigence system to evaluate chemosensitivity of ovarian cancer cells by measuring their colony volume but application of this method remains in the experimental phase. Optimization of ovarian cancer treatment would improve chemotherapy results, thus increasing the overall survival, improving the quality of patient life, decreasing chemotherapy-related toxicity and resulting in economic benefits owing to better drug use.

Preoperative detection of sentinel lymph nodes in endometrial cancer using SPECT/CT.

We report the use of SPECT/CT in sentinel lymph node biopsy in endometrial cancer. The patient was a 54-year-old woman with the diagnosis of endometrial adnenocarcinoma, grade 2. Preoperative MRI and transvaginal ultrasound scans revealed tumor infiltrating more than 50% of the myometrium. The patient was qualified for total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic/paraaortic lymphadenectomy. Before the surgery, 2 cervical injections of the (99m)Tc-labeled nanocolloid (0.5 mCi) were administered and the SPECT/CT was performed using a standard dual-head gamma camera and a 6-slice spiral CT component.

Comparison of SPECT-CT results and intraoperative detection of sentinel lymph nodes in endometrial cancer.

OBJECTIVES: The aim of the study was to compare the results of single-photon emission computed tomography-computed tomography (SPECT-CT) with those of intraoperative gamma probe detection and assess the clinical utility of SPECT-CT for sentinel lymph node biopsy in endometrial cancer. MATERIALS AND METHODS: We investigated 70 patients with endometrial cancer who underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and sentinel lymph node biopsy (routine pelvic and para-aortic lymphadenectomy was additionally performed in high-risk patients). Tc-99m radiocolloid albumin was injected into the cervix and a blue dye was injected superficially into the fundus. RESULTS: SPECT-CT revealed hot spots in 64 patients (91.4%). The detection rates were 97.1 and 94.3% using the combined technique and the hand-held gamma probe, respectively. In 19 cases (27.1%) 35 hot spots detected on SPECT-CT were not diagnosed as sentinel lymph nodes (SLNs) during surgery. In each patient with undetected hot spots located in the common iliac or para-aortic regions, hot SLNs were found during surgery in the obturator or external iliac region. In addition, SPECT-CT had detected 88.9% of the SLNs found during surgery. With respect to the 13 cases not detected on SPECT-CT, the hot SLNs had very low activity. Using the combined method, 95.1% of SLNs were found in typical locations (external iliac or obturator nodes). There were two metastatic nodes: one in SLN and one in nonsentinel node. CONCLUSION: SPECT-CT yields a high SLN detection rate; however, there is significant discrepancy in comparison with intraoperative findings, which limits its clinical utility. In addition, in the majority of cases SLNs are found in typical areas, which means that they can be reliably detected using an intraoperative gamma probe.

Sentinel lymph node detection with the use of SPECT-CT in endometrial cancer--analysis of two cases.

On the basis of two cases we discuss the important issues regarding the sentinel lymph node detection biopsy (SLNB) in endometrial cancer with combined cervical administration of the radiocolloid and the subserosal blue dye injection. The first patient (endometrioid adenocarcinoma G2, invasion > 50% myometrium) had 4 SLNs detected. Three were both hot and blue (detected on SPECT-CT). The fourth, paraaortic SLN was blue only. None of the lymph nodes contained metatstases. The second patient (endometrioid adenocarcinoma G1, invasion > 50% myometrium) had 4 SLNs detected. Three were blue (but two of them had also very low radioactivity). The fourth SLN was hot only. Blue only node contained macrometastasis. In the past patients underwent cervical amputation. Diverse distribution of each tracer confirms the advantages of the combined tracers administration in SLNB. The radiotracer is the crucial component--uptake was present in 6 of 8 SLNs. Although the blue dye is more a complimentary method, its suberosal injection significantly increases the safety of the SLNB procedure. In the first case we have detected blue only SLN in paraaortic region which otherwise would be missed using the cervical approach only. More importantly in the second case the tracer uptake was very limited due to the previous surgery and the blue dye administration allowed correct SLNs detection (including the metastatic node). Presented clinical cases confirms that the combined cervical and subserosal tracers administration together with preoperative SPECT-CT constitute an optimal SLN detection method and correctly provides information about the regional lymph node status.

The role of elastography in the differential diagnosis of endometrial pathologies--preliminary report.

OBJECTIVES: The aim of the study was to prove the possibility of elastography application in the assessment of the indications for dilatation and curettage (D&C) of the uterine cavity in patients with wide endometrium found in transvaginal ultrasound examination. MATERIAL AND METHODS: Analyzed group consisted of 25 perimenopausal women admitted for D&C due to the suspicion of endometrial hypertrophy. In all the patients transvaginal ultrasound examination in B-mode and elastography by the use of ElastoScan software were performed. Endometrium was described by Elastography Index (EI) presented in previous publications. The results were compared to the pathological results from D&C. RESULTS: Statistical analysis revealed significant difference of elastography image of endometrium described by EI between patients with normal or atrophic endometrium confirmed by pathological examination and women with abnormal findings--endometrial cancer hypertrophy or polyp (chi2 Pearson test; p=0.00005). EI in the group with normal endometrium was 0 or 1 point and in the group with endometrial pathology was from 2 to 4 points. No patient with EI for endometrium above 1 point had normal or atrophic endometrium and no woman with EI 0 or 1 had any pathologic finding. CONCLUSIONS: Elastography as a new diagnostic technique in gynecology seems to be a valuable tool differentiating endometrial pathologies from normal or atrophic endometrium in perimenopausal women with endometrium thickness above 5 mm in transvaginal ultrasound examination.

[Phalanges necrosis--a rare manifestation of "hand-foot" syndrome induced by gemcitabine used in the second--line therapy for progressive ovarian cancer. A case report]. / Zespól dloniowo-podeszwowy pod postacia martwicy palców rak. Przypadek rzadkiego powiklania w nastepstwie zastosowania gemcytabiny u chorej z zaawansowanym rakiem jajnika.

"Hand-foot" syndrome is a well-documented, dermatologic reaction after several chemotherapeutic agents with wild spectrum of symptoms. To the best of our knowledge, palmar-plantar erythrodysesthesia syndrome--presented as irreversible cytotoxic side effect induced by gemcitabine alone--has not been reported so far. We present a case of a patient with a history of peripheral sensory neuropathy who developed a painless finger necrosis caused by gemcitabine used in the second-line therapy for progressive ovary cancer.

Second line platinum-based intraperitoneal chemotherapy for advanced ovarian cancer.

OBJECTIVE: To report the results of ovarian cancer treatment, where a regimen of intravenous cyclophosphamide followed by intraperitoneal cisplatin or carboplatin was administered as second line treatment. DESIGN: Retrospective observational study on 198 women with stage I-IV histologically documented epithelial ovarian cancer after one or more prior regimens of chemotherapy. SETTING: University tertiary referral clinic, Gdansk, Poland. METHODS: The study group was recruited from among 593 ovarian cancer patients treated between January 1996 and December 2006. Conditions of inclusion for intraperitoneal treatment were: relapse or recurrence of disease after surgery followed by first line treatment. Recurrences were confirmed through re-staging laparotomy or second-look laparotomy. Patients received 90 mg/m(2) cisplatin, or carboplatin AUC 6 intraperitoneally and cyclophosphamide 750 mg/m(2) intravenously. Four or six courses were planned for each patient. MAIN OUTCOME MEASURES: Response to treatment defined as complete or partial response, or progressive disease, and survival rates. RESULTS: There were 67 (34%) with complete and 61 (31%) with partial response, while 69 (35%) developed progressive disease. Median survival from the initiation of intraperitoneal chemotherapy (IP) was 51 months and significantly longer for patients who received four cycles of IP: 78 months vs. 20 months for patients who received six intraperitoneal cycles. CONCLUSIONS: IP can be used in second line treatment of ovarian cancer, but six treatment cycles appear associated with worse results compared to four.

[Fertility of women after conservative operation for borderline ovarian tumors]. / Analiza plodnosci kobiet po leczeniu oszczedzajacym z powodu nowotworów jajnika o granicznej zlosliwosci.

OBJECTIVES: The aim of the study was to assess procreation in group of patients who were treated by conservative operation for borderline tumors of the ovary. DESIGN: The analysis included 42 patients conservatively operated for ovarian tumor of borderline malignancy in Department of Gynecology Medical University of Gdansk between 1978-2000. The incidence of pregnancy, age of patients, tumor pathology, type of conservative surgery and the course of pregnancy and labour were evaluated in this study. RESULTS: In the analysis group were 36 (85.7%) stage IA, 2 (4.8%) stage IB, 3 (7.1%) stage IC and 1 (2.4%) stage III C patients. Unilateral adnexectomy was performed in 36 (85.7%) patients, 4 (9.5%) unilateral cystectomy, 2 (4.8%) bilateral cystectomy with omentectomy in one case. After conservative operation 10 (23.8%) patients were pregnant and delivered healthy children but 2 patients delivered twice and 1 third. Recurrence was observed in 2 patients in period of 27 and 50 months after operation. 5 years survival was 97.6%. CONCLUSIONS: Percentage of pregnancy after conservative treatment for borderline ovarian tumors was high (23,8%) and number of recurrences was low so conservative surgery allows young women to retain procreational potential without increasing risk of recurrence.

[Burkitt lymphoma involving the ovaries]. / Lokalizacja guzów chloniaka Burkitta w jajnikach.

Burkitt lymphoma is a very rare type of lymphoma with a predilection for the ovary. We report a case of 18-years old woman with dramatic course of the Burkitt lymphoma involving ovaries. Immunohistochemistry techniques allowed for the diagnosis and the successful chemotherapy. The case demonstrates the importance of an appropriate pathology evaluation and interdisciplinary collaboration.

[Isolated metastases of cervical cancer to the abdominal wall--a case report]. / Nietypowa lokalizacja przerzutów raka plaskonablonkowego szyjki macicy do powlok brzusznych--opis przypadku.

We described an unusual case of skin metastases of the uterine cervix in 63 year old woman. Previously, she was found having a Stage IIa squamous carcinoma of the cervix. She underwent bilateral salpingo-oophorectomy, total abdominal hysterectomy and pelvic node dissection. Then the patient was treated by external and intracavitary radiation. Within the next six months she was readmitted to the hospital because of abdominal pain and urinary stress incontinence after irradiation. The examination revealed three firm, freely-movable, solid subcutaneous nodules on the abdominal wall, umbilical site and urinary fistula. No other significant physical phenomena were noted. Radical excision of all the lesions was conducted and followed by four courses of adjuvant chemotherapy. Histopathological examination of the excised nodules revealed nests of squamous cell carcinoma, which were histologically identical to the previous carcinoma of the cervix. After successful treatment, the patient was continued for three months now, without any clinical evidence of recrudescence, and with good results from the urinary fistula treatment. Moreover, in these case-report we presented a review of current literature about new techniques and treatment methods of the cervical carcinomas.

[Co-existence of myoma uteri and pregnancy]. / Ciaza powiklana obecnoscia miesniaków macicy.

OBJECTIVE: Myomas of uterus are the most common mild tumours of uterus. There is often observed the rapid increase of them during the pregnancy and then they could caused complications from 0.3% to 2.6% of pregnancies. DESIGN: The aim of study was the general valuation of the course and delivery means of the pregnancies coexisted with myoma uteri. MATERIALS AND METHODS: We have analysed 11 pregnancies, which we observed during hospitalisation of pregnant women at 2nd Department of Obstetrics and Gynaecology at Medical University of Gdansk. RESULTS: We observed pain in abdomen during pregnancy in 63.6% of analysed group. The 6 (54.5%) pregnant women were pharmacologically treated against symptoms of miscarriages and preterm labors. We investigated in the connection of the complicated pregnancy at women with myomatous uterus. The results confirm the high risk of the pregnancy. Almost 82% of analysed group delivered at time. The frequency of caesarean sections in our study was about 36%, but 2 of them were performed because of myomas. CONCLUSION: We made conclusion that pregnancy complicated by myomas had not significant increase in failure at the end. Myomatous uterus in pregnancy required to be quickly diagnosed and take care to prevent complications.

[An advanced cervical carcinoma coexisting with pregnancy in 19-years old primipara--a case report and review of current literature]. / Zaawansowany rak szyjki macicy wspólistniejacy z ciaza u 19-letniej pierwiastki--opis przypadku i przeglad pismiennictwa.

In our case report we described an fatal outcome of very young, nineteen years old primipara with advanced, aggressive squamous cervical cancer associated with 20 weeks gestation. Despite of our intentions to abort the pregnancy and started immediate therapy, she decided to delay treatment to allow fetal maturity. After 12 weeks interval, she was readmitted to the hospital with symptoms of intestinal occlusions caused by fast progression of disease. In 33 week of gestation we performed classical caesarean section with Pivercs type III radical hysterectomy. She was delivered of viable female infant weighing 1800 g. Simultaneously, we extended operation of possible cytoreductive surgery. After that, patient received two courses of adjuvant chemotherapy (MIC-scheme) and supplemental external beam radiation. Unfortunately, despite of multidisciplinary, aggressive treatment, she experienced recurrence in pelvic side walls within 6 months of surgery. At last follow-up, she was receiving salvage therapy.

[Neoadjuvant chemotherapy in the treatment of advanced cervical cancer]. / Zastosowanie chemioterapii indukcyjnej przed operacyjnym leczeniem zaawansowanego raka szyjki macicy.

UNLABELLED: Neoadjuvant chemotherapy (NAC) has been used for treatment of advanced cervical cancer by some institutions for several years. PURPOSE: We investigated the value of NAC for patients with IIb cervical cancer. MATERIALS AND METHODS: Eight patients treated at the 2nd Department of Obstetrics and Gynecology Medical University of Gdansk between 1999 and 2000 for stage IIb cervical cancer were enrolled into the study. The drugs infused were: cisplatin 50 mg/m(2) and vincristine 1 mg/m(2) for 1 day and bleomycin 25 mg/m(2) for 3 days, for three cycles. NAC was followed by radical Wertheim-Meigs hysterectomy. All patients were evaluated for response and toxicity. RESULTS: In all eight patients partial responses were obtained. Despite previous data there was no severe toxicity in our study group. Hematological toxicity was mild and there was no need for modifying chemotherapy due to side effect of NAC. CONCLUSION: NAC followed by radical Wertheim-Meigs hysterectomy is an effective approach to stage IIB cervical cancer. Further larger prospective study is necessary. Preoperative imaging studies (CT and/or MR) might be consider as selection criteria for future study.

[Lymph node metastasis as a prognostic factor in cervical carcinoma]. / Przerzuty do wezlów chlonnych jako czynnik prognostyczny raka szyjki macicy.

MATERIAL AND METHODS: 499 patients with cervical carcinoma at stage I and IIa after radical hysterectomy were included in the study. Diagnosis was based on gynecological examinations and cervical biopsies. Clinical staging was determined by FIGO classification. Pelvic lymph nodes were routinely removed on hysterectomy. RESULTS: Metastatic nodes were observed in 26.3% (131 patients). We found no metastatic nodes at stage Ia. In the group of 410 patients with stage Ib cervical cancer metastases in lymph nodes were found in 24.6% (101 patients). In the group of 78 patients with stage IIa cervical cancer metastatic nodes were observed in 38.5% (30 patients). In our finding metastases were located in one group of lymph nodes in 64.4% (64 patients) with stage Ib and 43.3% (13 patients) with stage IIa. Metastatic involvement of more than one group of lymph nodes was observed in 36.6% (37 patients) of stage Ib and 56.7% (17 patients) of stage IIa. The most frequent pattern of lymph nodes metastatic involvement comprised common iliac and obturatorious nodes. 5 year survival in the group without metastases in lymph nodes was estimated at 82.2%, and in the group with nodal metastases--50.8% (p = 0.005). CONCLUSIONS: 1. Metastases to pelvic lymph nodes are significant prognostic factor of long-term survival in patients with cervical cancer. 2. Patients with metastases in lymph nodes and no subsequent postoperative radiotherapy had significantly worse long-term survival.

[Paclitaxel hypersensitivity reactions in patients with advanced ovarian carcinoma]. / Reakcje nadwrazliwosci na paklitaksel u chorych z zaawansowanym rakiem jajnika.

OBJECTIVES: The purpose of our study was to analyze the rate of hypersensitivity reactions (HSRs) to paclitaxel in patients with advanced ovarian carcinoma. We also analyzed the possibility of re-administration paclitaxel with adequate treatment after hypersensitivity reactions. MATERIALS AND METHODS: The incidence of HSRs was analyzed retrospectively in 112 patients who received 24-hr infusions of paclitaxel (135 mg/m2) for advanced ovarian cancer at the Department of Gynecology Medical University of Gdansk between the January 2000 and the February 2002. Before each course of the paclitaxel administration patients received orally dexamethasone (20 mg p.o., 12 and 6 hours prior to the chemotherapy) and thirty minutes prior to the infusion of paclitaxel all patients received, diphenhydramine (50 mg), and cimetidine (300 mg) intravenously (i.v.). When HSR was observed administration of paclitaxel was temporally stopped and before the re-challenge additional intravenous dosage of hydrocortisone (200-500 mg) and diphenhydramine (25 mg) was given. RESULTS: Severe hypersensitivity reactions occurred in 9 patients (8%) and the administration of paclitaxel was withdrawn. Mild hypersensitivity reactions were observed in 8 patients (7%) and all of these patients were successfully retreated with paclitaxel without HSRs. CONCLUSION: We conclude that this premedication and treatment strategy provides lower hypersensitivity reactions rate and allows for continuing administration of paclitaxel in patients with advanced ovarian carcinoma.

[Evolution of surgical treatments in patients with borderline ovarian tumors]. / Ewolucja w postepowaniu chirurgicznym w nowotworach jajnika o granicznej zlosliwosci.

OBJECTIVES: The aim of this study was to evaluate a type and range of primary operation of patients with borderline ovarian tumours. MATERIAL AND METHODS: The analysis included 129 patients operated for ovarian tumours of borderline malignancy in the Gynaecological Department of Medical University of Gdansk between 1978-2000. The two types of primary operations were defined: conservative and radical. The dependency of type of operation on such factors as age of patients, parity, stage and histological type on was assessed. RESULTS: The group of 42 patients were treated with conservative surgery and 87 underwent radical treatment. 36 from 42 patients (85.7%) were treated by USO. A conservative surgery was mainly performed in young patients with mucinous borderline tumor in stage IA. The risk of recurrence was 4.8% in the group of patients treated conservatively and 8.0% in group of patients treated radically. 5-years survival was, 98.2% and 87.2% respectively. CONCLUSIONS: The type of the primary operation depends on age, parity, stage and histological type of borderline ovarian tumors. A conservative surgery is a proper treatment for young women with borderline ovary tumours in stage Ia. For older, perimenopausal women TAH with BSO is suggested.

[Comparison of quality of life in patients with advanced ovarian cancer treated with intraperitoneal or intravenous cisplatin and cyclophosphamide as a second line of therapy]. / Porównanie jakosci zycia chorych zaawansowanym rakiem jajnika otrzymujacych w drugiej linii leczenia cisplatyne z cykofosfamidem dootrzewnowo oraz dozylnie.

OBJECTIVES: The study aimed to compare the effect of second line intravenous and intraperitoneal chemotherapy on physical and psychological aspects of quality of life in patients with advanced ovarian cancer. MATERIALS AND METHODS: Quality of life was measured with EORTC QLQ-C30 (version 3.0) questionnaire. 42 sample patients with histologically confirmed diagnosis of advanced epithelial ovarian cancer treated with second line intravenous or intraperitoneal chemotherapy were included in the study. RESULTS: Higher score of global quality of life and less side-effects of chemotherapy were observed in the group of patients treated with intraperitoneal chemotherapy. In this group constipation and dyspnoea were less common. CONCLUSION: Intraperitoneal chemotherapy has less negative influence on quality of life than intravenous drug delivery.