Chemotherapy and PARP inhibitors in heavily pretreated BRCA1/2 mutation ovarian cancer (BMOC) patients.

OBJECTIVES: The hallmarks of germline(g) and/or somatic(s) BRCA1/2 mutation ovarian cancer (BMOC) patients are increased sensitivity to platinum-based chemotherapy (PCT) and PARP inhibitors (PARPi). There is little information on the effectiveness of chemotherapy in heavily pretreated (≥3 CT lines) g/sBMOC patients. METHODS: g/sBMOC patients who received CT from 2006 to 2016 at 4 cancer centers in Spain were selected. Overall survival (OS) and time to progression (TTP) were calculated with Kaplan Meier and Cox models. RESULTS: 135 g/sBMOC patients were identified (6% sBRCA1/2 mutations). The median number of chemotherapy lines was 2 (1-7). The 6-years OS rate was 69.4% and 71% in BRCA1 or BRCA2 mutation carriers (p = 0.98). A total of 57 (42%) patients had ≥3 CT lines (3-7), which encompassed a total of 155 treatments. The median overall TTP across all treatment lines beyond 2nd line was 10.2 months (CI 95% 8.4-11.9 months). In the platinum-sensitive setting, TTP was improved with PCT plus PARPi (17.1 m), PCT (12.6 m) or PARPi (12.4 m) versus non-PCT (4.9 m; p < 0.001 all comparisons). In the platinum-resistant setting, these differences in TTP were not statistically significant. A multivariate model confirmed that primary platinum-free interval (PFI) > 12 months and exposure to PCT and PARPi associated with improved outcomes. PARPi exposure did not compromise benefit of subsequent CT beyond 2nd relapse. CONCLUSIONS: Heavily pretreated g/sBMOC demonstrated CT sensitivity, including for non-PCT choices. Primary platinum-free interval (PFI) >12 months and exposure to both platinum-based chemotherapy and PARPi associate with improved prognosis in heavily pretreated g/sBMOC patients.

Is OSNA better than imprint cytology for intraoperative diagnosis of cancer involvement of axillary sentinel node in breast cancer?

OBJECTIVE: The study aim was to establish Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value (NPV), and Accuracy Values of both imprint cytology (IC) and the OSNA assay for intraoperative assessment of axillary sentinel node (SN) cancer involvement in breast cancer. Specifically, we wished to find out if true positive and false negative results of IC were associated to axillary lymphadenectomy (ALND). Also, we addressed a comparative cost analysis between techniques. METHODS: 244 patients treated for breast cancer in the Breast Unit of Hospital Germans Trias i Pujol from 2011 to 2015 were prospectively included. A transversal, consecutive design was applied to assess IC compared to the reference test (OSNA). Inclusion criteria were: T1 and T2 tumors with negative nodes, both clinically and on ultrasound. RESULTS: Sensitivity of IC for macrometastases was 70%. The NPV of IC for macrometastases was 95,75%. Accuracy of IC was 96,12%. In the comparative cost analysis, the release time of results for OSNA doubled that of IC and was associated with an increased cost of € 370. CONCLUSIONS: IC has been stated as a good technique for intraoperative cancer involvement SN with high sensitivity and NPV compared to the OSNA assay. It allows keeping the whole node tissue and thus the possibility of improved histopathological evaluation, which can be useful for adjuvant, and offers the advantage of being less time consuming. Cost analysis shows a higher cost for OSNA, which may exceed the benefit of sorting out false negatives from IC.

Correlation of 18F-FDG uptake on PET/CT with Ki67 immunohistochemistry in pre-treatment epithelial ovarian cancer. / Correlación de la captación de 18F-FDG de la PET/TC con el Ki67 de la inmunohistoquímica en el cáncer epitelial de ovario pretratamiento.

OBJECTIVE: Standardised uptake value (SUV) and volumetric parameters such as metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from 18F-FDG PET/CT are useful criteria for disease prognosis in pre-operative and post-treatment epithelial ovarian cancer (EOC). Ki67 is another prognostic biomarker in EOC, associated with tumour aggressiveness. The aim of this study is to evaluate the association between 18F-FDG PET/CT measurements and Ki67 in pre-treatment EOC to determine if PET/CT parameters could non-invasively predict tumour aggressiveness. MATERIAL AND METHODS: A pre-treatment PET/CT was performed on 18 patients with suspected or newly diagnosed EOC. Maximum SUV (SUVmax), mean SUV (SUVmean), whole-body MTV (wbMTV), and whole-body TLG (wbTLG) with a threshold of 30% and 40% of the SUVmax were obtained. Furthermore, Ki67 index (mean and hotspot) was estimated in tumour tissue specimens. Immunohistochemical findings were correlated with PET parameters. RESULTS: The mean age was 57.0 years old (standard deviation 13.6 years). A moderate correlation was observed between mean Ki67 index and SUVmax (r=0.392), SUVmean 30% (r=0.437), and SUVmean 40% (r=0.443), and also between hotspot Ki67 index and SUVmax (r=0.360), SUVmean 30% (r=0.362) and SUVmean 40% (r=0.319). There was a weaker correlation, which was inversely negative, between mean and hotspot Ki67 and volumetric PET parameters. However, no statistical significant differences were found for any correlations. CONCLUSIONS: SUVmax and SUVmean were moderately correlated with Ki67 index, whereas volumetric PET parameters overall, showed a weaker correlation. Thus, SUVmax and SUVmean could be used to assess tumour aggressiveness in pre-treatment EOC.

From interventionist imaging to intraoperative guidance: New perspectives by combining advanced tools and navigation with radio-guided surgery. / De la imagen intervencionista a la guía intraoperatoria: nuevas perspectivas combinando herramientas avanzadas y navegación con la cirugía radioguiada.

The integration of medical imaging technologies into diagnostic and therapeutic approaches can provide a preoperative insight into both anatomical (e.g. using computed tomography, magnetic resonance imaging, or ultrasound), as well as functional aspects (e.g. using single photon emission computed tomography, positron emission tomography, lymphoscintigraphy, or optical imaging). Moreover, some imaging modalities are also used in an interventional setting (e.g. computed tomography, ultrasound, gamma or optical imaging) where they provide the surgeon with real-time information during the procedure. Various tools and approaches for image-guided navigation in cancer surgery are becoming feasible today. With the development of new tracers and portable imaging devices, these advances will reinforce the role of interventional molecular imaging.

Use of SPECT/CT for improved sentinel lymph node localization in endometrial cancer.

OBJECTIVE: To assess the usefulness of adding SPECT/CT to planar images for pre-surgical sentinel lymph node (SLN) identification in endometrial cancer (EC), a technique that could have an important clinical impact on the staging, treatment, and prognosis of EC patients. METHODS: We compared the planar and SPECT/CT lymphoscintigraphic images of 44 patients with high-risk EC who underwent sentinel lymph node procedure (SLN) using an injection technique recently developed at our center known as TUMIR (Transvaginal Ultrasound Myometrial Injection of Radiotracer). 148 MBq (4 mCi) of 99mTc-nanocolloid were injected, guided by transvaginal ultrasound imaging. Planar and SPECT/CT images were performed in all 44 patients. RESULTS: SLNs were seen on planar images in 32 cases (73%) and in 34 cases (77%) using SPECT/CT. A total of 88 SLNs were depicted by planar lymphoscintigraphy while SPECT/CT visualized a total of 110 SLNs. SPECT/CT changed the assessment of the SLNs visualized in planar lymphoscintigraphy in 26 cases, either by modifying the number and/or the location of the SLNs detected. External iliac chain was the most frequent location of SLN detection (71%) in the 34 cases. Fifteen of these patients (44%) showed para-aortic SLNs. One case had exclusive para-aortic drainage (3%) that was only visualized by SPECT/CT. In another case, SPECT/CT was able to localize the only pelvic metastatic lymph node not visualized by planar images. CONCLUSIONS: SPECT/CT combined with planar imaging improves preoperative SLN detection and provides valuable anatomic information that enhances the presurgical stage of the SLN technique in endometrial cancer.

[Sentinel node in gynaecological cancers. Our experience]. / Ganglio centinela en cánceres ginecológicos. Nuestra experiencia.

UNLABELLED: Although sentinel lymph node (SLN) identification is widespread used in melanoma and breast cancer some concerns exist in other malignancies, such gynaecologic cancers, and this staging method has not been adopted in many centers due to lack or large validation studies. AIM: To evaluate the applicability and results of SLN technique in gynaecological malignancies referred to our institution. METHOD: We studied 155 patients with different malignancies (70 vulvar, 50 cervical and 35 endometrial cancers). The day before surgery a lymphoscintigraphy was performed by injecting 111 MBq of (99m)Tc-nanocolloid in several ways depending on the type of cancer studied. Intraoperative detection of the SLN was always performed by using a hand-held gammaprobe and, in 100 cases with the aid of blue dye injection (70 vulvar and 30 in cervical cancer) few minutes before surgical intervention. Pathological study of SLN was performed in all cases. Lymphadenectomy was done in all cervix and endometrial cancer patients and in the first 35 vulvar cancer patients. RESULTS: Pre-surgical lymphoscintigraphy demonstrated one, at least, SLN in 97% of vulvar cancer patients, 92% in the cervical malignancy and 64% in the endometrial cancer patients. During surgery, SLN was harvested in 97%, 90% and 62% of patients, respectively. The pathological study showed metastases in 24.2%, 8.8 and 4.5% of patients with vulvar, cervical and endometrial cancer, respectively. The false negative percentage was 5.5% in vulvar cancer patients, with 2 cases in the endometrial cancer and without any case in the cervical cancer patients. CONCLUSION: Lymphoscintigraphy is a relatively simple and useful technique to identify the SLN in this kind of tumours. However, in endometrial cancer more effort has to be made to reach a suitable result. Sentinel lymph node biopsy seems to be a reliable technique in vulvar and cervical malignancies.

Laparoscopic ovarian transposition in patients with early cervical cancer.

The aim of this study was to evaluate the feasibility, efficacy, and morbidity of laparoscopic ovarian transposition on the preservation of hormonal function in patients younger than 45 years operated for early cervical cancer. According to risk factors on pathologic evaluation of the specimen, some of them will receive postoperative pelvic radiotherapy. This subset of patients could benefit from taking the ovaries away from the irradiation field in an effort to preserve their functionality. This prospective study included 28 FIGO stage IB1 cervical cancer patients, 45 years old or younger, maintaining menstrual cycles, who were considered suitable for conservation of the ovaries. The ovarian transposition was performed by laparoscopy as a part of the same celio-Schauta operation. Twelve patients underwent adjuvant pelvic radiotherapy. No intraoperative or postoperative morbidity related to the ovarian transposition was observed, and the procedure only entailed a minimum delay of the operative time. There were no cases of ovarian metastasis. At a mean follow-up of 44 months, 63.6% of patients receiving radiotherapy and 93% of those who nonirradiated maintained normal ovarian function. Two patients developed benign ovarian cysts, requiring oophorectomy, but no other long-term adverse effects of the transposition were identified. To the best of our knowledge, this is the largest series of the laparoscopic procedure reported to date in this setting. According to our results, laparoscopic ovarian transposition is a safe and effective procedure for the preservation of ovarian function in young patients with early cervical cancer undergoing adjuvant radiotherapy after surgery.

Preoperative and intraoperative assessment of myometrial invasion and histologic grade in endometrial cancer: role of magnetic resonance imaging and frozen section.

The objective of this study was to determine the value of myometrial invasion by magnetic resonance imaging (MRI), histologic typing and grading by endometrial biopsy, and the intraoperative evaluation of both parameters by frozen section in the evaluation of endometrial cancer. The preoperative and intraoperative records of 180 patients with endometrial cancer were used to compare the preoperative endometrial biopsy, the myometrial invasion by MRI, and the intraoperative frozen sections, with the final histopathologic findings. The preoperative endometrial biopsy gave us the tumor histologic type and grade. MRI gave us the depth of myometrial invasion. The evaluation of intraoperative frozen sections gave us the tumor histologic type, the tumor grade, and also the myometrial invasion. Patients were classified as low risk (grade 1 and 2, and myometrial invasion <50%) and high risk (grade 3 or myometrial invasion >50%). Standard statistical calculations were used. Evaluation of the tumor grade by preoperative biopsy has a sensitivity and a specificity of 75% and 95%, respectively. Evaluation of the tumor grade by intraoperative biopsy has a sensitivity and a specificity of 40% and 98%, respectively. Evaluation of the depth of myometrial invasion with MRI has a sensitivity and a specificity of 79% and 82%, respectively. Evaluation of the depth of myometrial invasion with intraoperative frozen sections has a sensitivity and a specificity of 74% and 95%, respectively. Evaluation of all four of the parameters together has a sensitivity and a specificity of 80% and 82%, respectively with a kappa of 0.621. In our opinion, the combination of preoperative biopsy and intraoperative frozen section is the best way to decide whether a lymphadenectomy is necessary with a low rate of understaging patients. MRI would have a fringe benefit in these patients.

Port-site metastasis after laparoscopic surgery for endometrial carcinoma: two case reports.

BACKGROUND: Although studies have reported good results with laparoscopic-assisted vaginal hysterectomy (LAVH) to treat endometrial cancer, it has been associated with recurrent disease at trocar insertion sites. Long-term follow-up is necessary to detect possible adverse effects of this technique. CASES: We present two case reports of stage IIB endometrial cancer with port-site metastasis 39 and 48 months after initial surgery with LAVH. CONCLUSION: Although LAVH is a good technique to treat patients with endometrial cancer, port-site metastasis is a possible complication and should be taken into consideration until a randomized study shows the long-term benefits and risks of laparoscopic over standard treatment.

Visible and non-visible endometriosis at laparoscopy in fertile and infertile women and in patients with chronic pelvic pain: a prospective study.

In 100 consecutive patients who were undergoing laparoscopy for infertility (group 1, n = 52), chronic pelvic pain (group 2, n = 18) or tubal sterilization (group 3, n = 30, asymptomatic fertile women), peritoneal biopsies were taken from areas of visually normal peritoneum of uterosacral ligaments. Twenty-six patients in group 1 (50%), eight patients in group 2 (44.4%) and 13 patients in group 3 (43.3%), were found to have laparoscopic evidence of endometriosis elsewhere in the pelvis. The majority of women (80.7% in group 1, 87.5% in group 2, and 100% in group 3) had stage I disease. The incidence of the distinctive appearances of the lesions was similar in the three groups of patients and 7% of all women or 15% (7/47) of those patients having endometriosis at laparoscopy had only subtle (non-¿typical') endometriotic peritoneal lesions. Uterosacral biopsies showed the presence of endometriotic tissue in three cases (5.7%), two cases (11%) and three cases (10%) in groups 1, 2, and 3 respectively. One of the two patients in group 2 and two of the three patients in group 3 had no evidence of endometriosis at laparoscopy; thus histological study revealed the presence of endometriosis in normal peritoneum in 11% (5/47) of patients having macroscopic endometriosis and in 6% (3/53) of patients without endometriosis at laparoscopy. Previous oral contraceptive users were significantly higher among women having macroscopic and/or microscopic endometriosis than among women without the condition. In conclusion, our prospective study shows a high prevalence (45-50%) of endometriosis (including microscopic forms) in both patients with chronic pelvic pain and asymptomatic women (fertile and infertile), thus supporting the modern concept that in many women endometriosis may be a paraphysiological condition while probably only in some patients small amounts of endometriosis are an ¿annoyance' with implications to their reproductive health and may produce symptoms (e.g. pelvic pain) and therefore should be defined as a ¿dis-ease'. Previous use of oral contraceptives may increase the risk of developing endometriosis.

Massive metastases from a lobular breast carcinoma from an unknown primary during pregnancy. A case report.

BACKGROUND: Carcinoma of the breast during pregnancy represents 2-5% of all breast cancers. The frequency and histopathologic spectrum of breast cancer are similar in pregnant and nonpregnant women. Infiltrating lobular carcinoma is one of the less understood types of breast cancer, and its metastatic pattern seems to be different from that of infiltrating ductal carcinoma. Breast neoplasms rarely present as cancer from an unknown primary site. CASE: A woman in the third trimester of pregnancy developed carcinoma massively metastatic to the bone marrow and liver from an unknown primary tumor. At 32 weeks' gestation a healthy male was delivered by cesarean section. The patient died 12 hours after delivery. The autopsy revealed an infiltrating lobular carcinoma, 1.5 cm, of the breast. CONCLUSION: Massive metastases from an occult lobular breast carcinoma in a pregnant woman are very rare. Diffuse metastatic spread, which often complicates or delays the diagnosis, is a characteristic pattern of infiltrating lobular carcinoma. Cancer from an unknown primary site during pregnancy is an exceptional finding. If a metastatic adenocarcinoma is diagnosed in a pregnant woman, a breast primary should be strongly suspected.