Cytodiagnosis of bilateral abdominopelvic masses in a postmenopausal woman.

Cytologic diagnosis of ovarian low-grade serous carcinoma.

MRI-guided adaptive brachytherapy in locally advanced cervical cancer (EMBRACE-I): a multicentre prospective cohort study.

BACKGROUND: The concept of the use of MRI for image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer was introduced 20 years ago. Here, we report on EMBRACE-I, which aimed to evaluate local tumour control and morbidity after chemoradiotherapy and MRI-based IGABT. METHODS: EMBRACE-I was a prospective, observational, multicentre cohort study. Data from patients from 24 centres in Europe, Asia, and North America were prospectively collected. The inclusion criteria were patients older than 18 years, with biopsy-proven squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, The International Federation of Gynecology and Obstetrics (FIGO) stage IB-IVA disease or FIGO stage IVB disease restricted to paraaortic lymph metastasis below the L1-L2 interspace, suitable for curative treatment. Treatment consisted of chemoradiotherapy (weekly intravenous cisplatin 40 mg/m2, 5-6 cycles, 1 day per cycle, plus 45-50 Gy external-beam radiotherapy delivered in 1·8-2 Gy fractions) followed by MRI-based IGABT. The MRI-based IGABT target volume definition and dose reporting was according to Groupe Européen de Curiethérapie European Society for Radiation Oncology recommendations. IGABT dose prescription was open according to institutional practice. Local control and late morbidity were selected as primary endpoints in all patients available for analysis. The study was registered with ClinicalTrials.gov, NCT00920920. FINDINGS: Patient accrual began on July 30, 2008, and closed on Dec 29, 2015. A total of 1416 patients were registered in the database. After exclusion for not meeting patient selection criteria before treatment, being registered but not entered in the database, meeting the exclusion criteria, and being falsely excluded, data from 1341 patients were available for analysis of disease and data from 1251 patients were available for assessment of morbidity outcome. MRI-based IGABT including dose optimisation was done in 1317 (98·2%) of 1341 patients. Median high-risk clinical target volume was 28 cm3 (IQR 20-40) and median minimal dose to 90% of the clinical target volume (D90%) was 90 Gy (IQR 85-94) equi-effective dose in 2 Gy per fraction. At a median follow-up of 51 months (IQR 20-64), actuarial overall 5-year local control was 92% (95% CI 90-93). Actuarial cumulative 5-year incidence of grade 3-5 morbidity was 6·8% (95% CI 5·4-8·6) for genitourinary events, 8·5% (6·9-10·6) for gastrointestinal events, 5·7% (4·3-7·6) for vaginal events, and 3·2% (2·2-4·5) for fistulae. INTERPRETATION: Chemoradiotherapy and MRI-based IGABT result in effective and stable long-term local control across all stages of locally advanced cervical cancer, with a limited severe morbidity per organ. These results represent a positive breakthrough in the treatment of locally advanced cervical cancer, which might be used as a benchmark for clinical practice and all future studies. FUNDING: Medical University of Vienna, Aarhus University Hospital, Elekta AB, and Varian Medical Systems.

Impact of three-dimensional chemoradiation on pelvic bone mineral density, low back pain, and disability in cervical cancer: a prospective study.

OBJECTIVE: To prospectively analyze the effect of three-dimensional chemoradiation on the bone mineral density of pelvic bones and its association with low back pain and disability in patients with locally advanced cervical cancer. METHODS: In biopsy proven locally advanced cervical cancer patients, bone mineral density and T scores for lumbar vertebrae 5, dorsal thoracic vertebrae 12, and T scores for the femoral neck were analyzed. Low back pain was scored using the visual analog scale while disability scoring was done using the Oswestry low back pain disability scale. Furthermore, a subgroup analysis for patients (classified according to menopausal status) was performed. RESULTS: In total, 106 patients were analyzed. A statistically significant decline in mean bone mineral density was observed at all three sites (vertebrae 5 and 12, and the femoral neck) post-chemoradiation therapy compared with pretreatment bone mineral density (0.671 vs 0.828, -2.083 vs -1.531, -2.503 vs -1.626; all p<0.001). Similarly, in subgroup analyses, at all three sites, pre-menopausal patients showed a statistically significant association (0.876 vs 0.697, -1.203 vs -0.2.761, -1.403 vs -2.232; all p<0.001) while a non-significant association was observed for post-menopausal patients at vertebrae 12 (-1.707 vs -1.719; p=0.09) with a statistically significant association at vertebrae 5 and the femoral neck (0.803 vs 0.656, -1.746 vs -2.648; p<0.01). Although statistically significant low back pain and disability scores were observed overall and irrespective of menopausal status, no correlation between bone mineral density and low back pain and disability was observed. CONCLUSION: Pelvic bone mineral density decreases significantly after chemoradiation, irrespective of menopausal status. However, no correlation with low back pain and disability was observed. Pelvic bone mineral density analysis should be considered before chemoradiation in cervical cancer.

Practical aspects of palliative care & palliative radiotherapy in incurable cervical cancer.

Cervical cancer is the most common cause of cancer-related deaths among economically disadvantaged women. The symptoms of pain, discharge, constipation, foul smell, insomnia and depression can be controlled with inexpensive medicines such as oral morphine, maintenance oral metronidazole, antidepressants and laxatives. These medications should be prescribed according to the palliative care guidelines and titrated to the individual patient's clinical response, pathophysiology, and metabolic parameters. A hypothetical clinical scenario illustrates some aspects of pain and symptom management, inter-disciplinary palliative care, medical ethics and communication needs in low-resource settings. Palliative radiotherapy is a cost-effective intervention to reduce vaginal discharge, bleeding, pressure effects and nociceptive or neuropathic pain caused by pelvic and para-aortic disease. The role of palliative radiotherapy in patients with malignant fistulae is discussed and the literature on hypo-fractionated pelvic radiotherapy is briefly reviewed.

ALDH1 & CD133 in invasive cervical carcinoma & their association with the outcome of chemoradiation therapy.

Background & objectives: Chemoradiation is the standard therapy for locally advanced invasive cervical cancer and response to treatment determines the outcome. Cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) play a role in response to treatment and hence the aim of this study was to evaluate if their levels in pre-treatment biopsies by immunohistochemistry (IHC) could predict response to treatment and outcome. Methods: The study comprised 60 patients with FIGO Stage IIB/III invasive cervical carcinoma treated by chemoradiation. They were divided into two groups based on their clinical outcome: group 1, 30 patients who had no evidence of disease at 48 month follow up and group 2, 30 patients who had disease relapse within 6-12 months of treatment completion. IHC was performed for CSC markers (ALDH1, CD133, Nanog and Oct-4), EMT markers (E-cadherin and vimentin) and squamocolumnar junction (KRT7) markers and H-scores determined. Intergroup comparison was performed. The expression of these markers was also evaluated in histological sections of cervical pre-cancer (CIN1 and CIN3) in comparison to normal cervix. Results: Cervical Intraepithelial Neoplasia grade 3 (CIN3) showed high expression of ALDH1 and KRT7 as compared to normal cervical epithelium. Aldehyde dehydrogenase 1 (ALDH1) and CD133 were overexpressed in 70 and 24 per cent cervical carcinoma cases whereas E-cadherin showed reduced expression in invasive carcinoma as compared to normal controls. ALDH1 overexpression was significantly associated with disease relapse in invasive cervical carcinoma treated by chemoradiation (P<0.01). Interpretation & Conclusions: Determination of ALDH1 levels in pre-treatment cervical biopsies of invasive cervical carcinoma may be useful for prediction of response to chemoradiation, with high levels predicting for a poor response.

Cytomorphological features of cervical small cell neuroendocrine carcinoma in SurePath™ liquid-based cervical samples.

Small cell neuroendocrine carcinoma (SCNEC) of the cervix is a rare, highly aggressive tumour with poor prognosis and high propensity for distant metastases. The cytological features of SCNEC have rarely been described in cervical samples, and to the best of our knowledge, there are no previous reports using SurePath™ liquid-based cytology. In the present report we present the cytomorphological features of histopathologically confirmed cases of cervical SCNEC in SurePath preparations. On cytological examination, all three cases demonstrated variable numbers of tumour cells, ranging from a few dispersed cells and tiny micro-biopsies to large aggregates of small tumour cells with a high nucleus-to-cytoplasmic ratio, stippled chromatin, inconspicuous nucleoli, and scant cytoplasm. Immunocytochemistry for CD56 on the cervical preparation confirmed the diagnosis in one case. The presence of small tumour cells with characteristic stippled/salt-and-pepper type nuclear chromatin were the most consistent cytological features in these cases. Knowledge of these characteristic cytological features can help in suggesting a diagnosis of SCNEC in cervical samples which can then be confirmed by immunocytochemistry.

Health-related quality of life among cervical cancer patients in India.

INTRODUCTION: Estimation of health-related quality of life of cervical cancer patients in India is important in assessing the well-being of patients, monitor treatment outcomes, and conduct health technology assessments. However, health-related quality of life estimates for different stages of cervical cancer are not available for the Indian population. This study aims to generate stage-specific quality of life scores for cervical cancer patients in India. METHODS: A cross-sectional study using the EQ-5D (EuroQol 5-dimensions) instrument, that consists of the EQ-5D-5L descriptive system and the EuroQol Visual Analog Scale (EQ-VAS) was conducted. A total of 159 cervical cancer patients were interviewed. Mean EQ-5D-5L quality of life scores (utility scores) were calculated using the EQ-5D-5L index value calculator across different stages of cervical cancer. The proportion of patients reporting problems in different attributes of EQ-5D-5L was assessed. The impact of socio-economic determinants on health-related quality of life was evaluated using multiple linear regression. RESULTS: The mean EQ-5D-5L and EQ-VAS utility scores among patients of cervical cancer were 0.64 [95% CI=0.61-0.67] and 67.6 [95% CI=65.17-70.03], respectively. The most frequently reported problem among cervical cancer patients was pain/discomfort (61.88%), followed by difficulty in performing usual activities (53.81%), and anxiety/depression (41.26%). CONCLUSION: Cervical cancer significantly impacts the health-related quality of life of the patients in India. Clinical interventions should focus on the control of pain and relief of anxiety. The measurement of health-related quality of life should be an integral component of the effectiveness of interventions as well as health technology assessment.

Toxicity and clinical outcomes with definitive three-dimensional conformal radiotherapy (3DCRT) and concurrent cisplatin chemotherapy in locally advanced cervical carcinoma.

OBJECTIVE(S): This study aimed to retrospectively evaluate the toxicity and clinical outcomes in patients of locally advanced cervical cancer treated with three-dimensional conformal radiotherapy (3DCRT) and concurrent chemotherapy. MATERIAL AND METHODS: Two hundred and ten newly diagnosed patients of locally advanced cervical cancer of FIGO 2009 Stage II-III treated with 3DCRT (46 Gy/23 fractions/4½ weeks) and weekly concurrent Cisplatin (40 mg/m2), from January 2013 to 2015 were analyzed. A planning computed tomography was performed and contouring was done according to published guidelines. External radiotherapy was followed by Intracavitary brachytherapy delivered to a dose of 9 Gy HDR in 2-fractions, given one week apart. The endpoints were treatment related toxicities and clinical outcomes. Local control (LC), overall survival (OS) and disease free survival (DFS) were evaluated and toxicities were documented using the common terminology criteria for adverse events (v3.0) (CTCAE). RESULTS: The median follow up time was 37 (range, 19-54) months. The 3 year OS, DFS and LC were 84.2%, 80.6% and 81% respectively. Grade ≥3 acute skin, upper and lower gastrointestinal (GI) and genitourinary (GU) toxicity was observed in 3 (1.4%), 11 (5.2%), 12 (5.7%) and 0 (0%) patients, respectively. Grade ≤2 hematological toxicity was observed in 154 (73.3%) patients. Grade ≥3 late GI and GU toxicity was seen in 9 (4.2%) patients and 2 (0.9%) patients, respectively. CONCLUSION: 3DCRT with concurrent chemotherapy results in good loco-regional control with acceptable normal tissue toxicity. In the background of indeterminate evidence regarding routine practice of intensity modulated radiotherapy in carcinoma of the cervix, 3DCRT may be considered as the treatment of choice.

Formulation of normal tissue irradiation volumes in Co-60 and Ir-192 HDR ICBT of Ca cervix using Total Reference Air Kerma (TRAK).

AIM: The aim of this study was to formulate isodose volume relations encompassed by isodose surfaces in Co-60 and Ir-192 HDR intracavitary brachytherapy (ICBT) of cervix carcinoma using the Total Reference Air Kerma (TRAK). BACKGROUND: The TRAK and isodose volumes are radioactive source related. The formulated relations can easily estimate the irradiated isodose volume if the TRAK and dose are known. The C0-60 can also be used for brachytherapy because of its longer half life and comparable OAR doses to Ir-192. MATERIALS AND METHODS: Isodose volumes encompassed by different isodose surfaces and TRAK were obtained from 22 Ca cervix ICBT treatment plans in Co-60 and Ir-192 HDR brachytherapy with 9 Gy prescription to point A. Isodose volume relations were formulated both for Co-60 and Ir-192 brachytherapy source from the slopes and intercepts of the linear fit in the plot between isodose volumes and TRAKs. RESULTS: The TRAK value of Co-60 was higher than Ir-192 by about 7.16%. The isodose volumes at low doses for Co-60 were higher than Ir-192. But no significant differences in the dose to the bladder and rectum were observed due to these sources. For dose to 2 cm3 bladder and rectum volume, the differences were 1.07% and 0.75%, respectively. The correlation coefficient with the 2-tailed significance of correlation (p value) between TPS measured isodose volume and calculated isodose volumes using the formulated relations at different dose values were statistically significant as p < 0.05. CONCLUSION: Results show different isodose volumes for both sources but the dose to the bladder and rectum are nearly the same.

The chemotherapy response score is a useful histological predictor of prognosis in high-grade serous carcinoma.

AIMS: High-grade serous carcinoma (HGSC) is the most common tubal/ovarian malignant tumour, and usually presents at an advanced stage. Interval debulking surgery (IDS) after neoadjuvant chemotherapy (NACT) is being increasingly used for the management of these patients. The chemotherapy response score (CRS) has been proposed for grading the response of tubo-ovarian HGSC to NACT on the basis of examination of IDS specimens. Our aims were to evaluate the CRS in post-NACT cases, assess the interobserver agreement, and correlate it with overall and progression-free survival. METHODS AND RESULTS: The CRS was applied by two independent pathologists on omental and adnexal tumour tissue sections from post-NACT patients with HGSC who had undergone IDS. The assigned primary site of tumour origin was documented. The interobserver agreement and prognostic significance of the CRS were evaluated. There were 103 cases, and in 61.1% of cases a fallopian tubal origin was confirmed. There were 26, 35 and 42 cases with CRSs of 1, 2, and 3, respectively. The interobserver variability for CRS was low (κ = 0.806). The CRS showed a significant correlation with progression-free survival (CRS 1 and 2 versus 3: median survival 16 months versus 18 months; P = 0.004); however, after controlling for debulking status, this association was not significant. The CRS applied to adnexal sections did not show any prognostic significance for either progression-free or overall survival. CONCLUSION: The CRS is an easy and reproducible method for predicting the prognosis in post-NACT HGSC patients.

Diffuse large B cell lymphoma of hard palate: a case report with literature review.

OBJECTIVE: Lymphomas are diverse group of neoplasm affecting the lymphoreticular system. Diffuse large B cell lymphoma is the most frequently diagnosed type of non-Hodgkin lymphoma and is the fifth most frequent malignancy, accounting for about 40% of cases reported. In the present case report a 40 year old female patient complains of swelling on right side of face since 45 days and gradually increased to present size. Intra-orally an ulcero-proliferative growth was present on the right side of hard palate. Incisional biopsy was suggestive of Lymphoproliferative disorder. Panel of immunohistochemical antibodies were used; which showed positivity for CD45, PAX5, Bcl2, Ki67, CD138 and negativity for CD3, CD10, CD20 and CD30. Therefore through routine standard hematoxylin and eosin staining a clear cut diagnosis of specific lymphoma was difficult to obtain and thus immunohistochemistry plays an important role in confirming the pinpoint diagnosis.

Gynecological Cancer as a Second Malignancy in Patients With Breast Cancer.

PURPOSE: The aim of this study was to determine the incidence and risk factors for gynecological cancer as second malignancy (SM) after treatment of breast cancer (BC). METHODS AND MATERIALS: Between January 1985 and December 2007, a total of 2756 patients with BC were analyzed for gynecological cancers as an SM. Analysis was carried out for patient-, disease-, and treatment-related characteristics. The Cox proportional hazards regression model was used to estimate the relative risk of gynecologic malignancies. RESULTS: The median age at BC diagnosis was 49 years and median follow-up of 14 years. In total, 25 cases of gynecological cancer were noted with an incidence of 0.9%. We observed 9 ovarian and endometrium (0.3%) as well as 7 uterine cervix (0.25%) cancers. Family history of BC was the most significant risk factor for SM (relative risk, 7.4; 95% confidence interval, 3.03-18.28; P<0.001). Women with a family history of BC had a higher incidence of endometrial (12%) and ovarian (16%) cancer compared with those who have no family history (0.1%, P = 0.003). Statistically significant higher incidence of endometrial cancer was seen in patients undergoing hormonal therapy (0.4%) as compared with those who are not undergoing hormonal therapy (0.1%, P = 0.001). Most of the endometrial (88.9%) and cervical (71%) cancers were detected at an early stage but ovarian cancers (66.6%) in advanced stage. Chemotherapy and radiotherapy did not increase the risk of gynecological SM. CONCLUSIONS: Women with BC are at risk of developing a second primary gynecological malignancy particularly of endometrium and ovary. Family history of BC was a high risk factor for gynecologic SM. These patients should be followed up for its early detection.

Why Newly Diagnosed Cancer Patients Require Supportive Care? An Audit from a Regional Cancer Center in India.

PURPOSE: The present study was planned to record the distressing symptoms of newly diagnosed cancer patients and evaluate how the symptoms were addressed by the treating oncologists. MATERIALS AND METHODS: All newly diagnosed cancer patients referred to the Department of Radiotherapy during May 2014 were asked to complete a questionnaire after taking their consent. The Edmonton symptom assessment scale-regular questionnaire was used to assess the frequency and intensity of distressing symptoms. The case records of these patients were then reviewed to compare the frequency and intensity documented by the treating physician. The difference in the two sets of symptoms documented was statistically analyzed by nonparametric tests using SPSS software version 16. RESULTS: Eighty-nine patients participated in this study, of which only 19 could fill the questionnaire on their own. Anxiety was the most common symptom (97.8%) followed by depression (89.9%), tiredness (89.9%), and pain (86.5%). The treating physicians recorded pain in 83.1% whereas the other symptoms were either not documented or grossly underreported. Anxiety was documented in 3/87 patients, but depression was not documented in any. Tiredness was documented in 12/80 patients, and loss of appetite in 54/77 patients mentioning them in the questionnaire. Significant statistical correlation could be seen between the presence of pain, anxiety, depression, tiredness, and loss of appetite in the patients. CONCLUSION: The study reveals that the distressing symptoms experienced by newly diagnosed cancer patients are grossly underreported and inadequately addressed by treating oncologists. Sensitizing the oncologists and incorporating palliative care principles early in the management of cancer patients could improve their holistic care.

Pelvic nodal CTV from L4-L5 or aortic bifurcation? An audit of the patterns of regional failures in cervical cancer patients treated with pelvic radiotherapy.

OBJECTIVE: To assess the patterns of recurrence in cervical cancer patients treated with pelvic nodal clinical target volume at L4-L5 junction instead of aortic bifurcation. METHODS: Records of patients with locally advanced cervical cancer treated with chemo-radiation were reviewed. Patients treated with standard pelvic fields (superior border of the field at L4/L5 junction), without any radiological evidence of regional lymphadenopathy (<10 mm) were included in the study. The level of aortic bifurcation was retrospectively documented on computed tomography. Patterns of recurrences were correlated to the aortic bifurcation and the superior border of the radiation fields (L4/L5). RESULTS: Aortic bifurcation was above the radiation fields (above L4/5) in 82 of 116 (70.7%) patients. Of the nine patients that recurred above the radiation field, 5 (55%) were above L4/5 failures, i.e. between aortic bifurcation and L4/5, and 4 (45%) had para-aortic failures. On retrospective analysis, 16 patients were found to have subcentimeter lymph nodes and higher nodal failures (7/16) were observed in patients with subcentimeter regional lymph nodes at diagnosis. CONCLUSIONS: Superior border of nodal clinical target volume should ideally include the aortic bifurcation instead of L4-L5 inter space in patients with locally advanced cervical cancer. Radiotherapy fields need to be defined cautiously in patients with subcentimeter pelvic lymph nodes.

Primitive neuroectodermal tumor of the uterine cervix diagnosed during pregnancy: a rare case with review of literature.

Primitive neuroectodermal tumors of the cervix are very rare. A 28-year-old pregnant woman presented with a cervical mass. The tumor was staged as IB2. The biopsy from tumor was suggestive of malignant small round cell tumor. She then underwent termination of pregnancy followed by radical hysterectomy. Based on morphologic and immunohistochemical profile, a diagnosis of peripheral primitive neuroectodermal tumor of the cervix was made. The patient received adjuvant chemotherapy and radiotherapy. The patient is alive and disease-free 33 months post-surgery. The present case highlights the importance of keeping primitive neuroectodermal tumors in the differential diagnosis of small cell neoplasms of the uterine cervix. Pregnancy should not be a barrier to early detection and treatment of this potentially aggressive tumor. The optimal treatment methods have not yet been established because of the rarity of the tumor.

CT and MR image fusion of tandem and ring applicator using rigid registration in intracavitary brachytherapy planning.

The purpose of this study is to find the uncertainties in the reconstruction of MR compatible ring-tandem intracavitary applicators of high-dose rate image-based brachytherapy treatment planning using rigid registration of 3D MR and CT image fusion. Tandem and ring reconstruction in MR image based brachytherapy planning was done using rigid registration of CT and MR applicator geometries. Verifications of registration for applicator fusion were performed in six verification steps at three different sites of tandem ring applicator set. The first site consists of three errors at the level of ring plane in (1) cranio caudal shift (Cranial Shift) of ring plane along tandem axis, (2) antero-posterior shift (AP Shift) perpendicular to tandem axis on the plane containing the tandem, and (3) lateral shift (Lat Shift) perpendicular to the plane containing the tandem at the level of ring plane. The other two sites are the verifications at the tip of tandem and neck of the ring. The verification at the tip of tandem consists of two errors in (1) antero-posterior shift (AP Shift) perpendicular to tandem axis on the plane containing the tandem, and (2) lateral shift (Lat Shift) perpendicular to the plane containing the tandem. The third site of verification at the neck of the ring is the error due to the rotation of ring about tandem axis. The impact of translational errors from -5 mm to 5 mm in the step of 1 mm along x-, y-, and z-axis and three rotational errors about these axes from -19.1° to 19.1° in the step of 3.28° on dose-volume histogram parameters (D(2cc), D(1cc), D(0.1cc), and D(5cc) of bladder, rectum, and sigmoid, and D90 and D98 of HRCTV were also analyzed. Maximum registration errors along cranio-caudal direction was 2.2 mm (1 case), whereas the errors of 31 out of 34 cases of registration were found within 1.5 mm, and those of two cases were less than 2mm but greater than 1.5 mm. Maximum rotational error of ring about tandem axis was 3.15° (1.1 mm). In other direction and different sites of the ring applicator set, the errors were within 1.5 mm. The impacts of registration errors on DVH parameters of bladder, rectum, and sigmoid were very sensitive to antero-posterior shift. Cranio-caudal errors of registration also largely affected the rectum DVH parameters. Largest change of 17.95% per mm and 20.65% per mm in all the DVH parameters of all OARs and HRCTV were observed for ϕ and Ψ rotational errors as compare to other translational and rotational errors. Catheter reconstruction in MR image using rigid registration of applicator geometries of CT and MR images is a feasible technique for MR image-based intracavitary brachytherapy planning. The applicator regis-tration using the contours of tandem and neck of the ring of CT and MR images decreased the rotational error about tandem axis. Verification of CT MR image fusion using applicator registration which consists of six steps of verification at three different sites in ring applicator set can report all the errors due to translation and rotational shift along θ, ϕ, and Ψ. ϕ and Ψ rotational errors, which produced potential changes in DVH parameters, can be tackled using AP Shift and Lat Shift at the tip of tandem. The maximum shift was still found along the tandem axis in this technique.

Association between the regular use of vaginal dilators and/or sexual activity and vaginal morbidity in locally advanced cervical cancer survivors - An EMBRACE-I study report.

PURPOSE: To provide risk estimations for vaginal morbidity with regard to vaginal dilation (summarizing the use of dilators and/or sexual activity) in locally advanced cervical cancer patients (LACC) treated with definitive radiochemotherapy and image-guided adaptive brachytherapy (IGABT) within the prospective, multi-institutional EMBRACE-I study. MATERIAL/METHODS: Physician-assessed vaginal morbidity (CTCAEv3.0), use of vaginal dilators and patient-reported sexual activity (EORTC-CX24) were prospectively assessed at baseline and during regular follow-up. Frequency analysis for vaginal dilation was performed in a sub-cohort of patients with ≥3 follow-ups. Regular dilation was defined if reported in ≥50% of follow-ups, no/infrequent dilation if reported in <50%. Actuarial estimates were calculated with Kaplan-Meier method; comparisons evaluated with the log-rank test. Univariate and multivariable Cox proportional hazard regression were used to evaluate risk factors for vaginal stenosis G≥2. RESULTS: The EMBRACE-I study included a total of 1416 patients (2008-2015); 882 were evaluated in the present report with a median follow-up of 60 months. Of those, 565 (64%) reported regular dilation. This was associated with a significantly lower 5-year risk of vaginal stenosis G≥2 compared to no/infrequent dilation (23% vs. 37%, p≤0.001). This univariate finding was confirmed by multivariable analysis, after adjusting for other risk factors (HR=0.630, p=0.001). Regular vaginal dilation was also associated with a significantly higher risk for vaginal dryness G≥1 (72% vs. 67%, p=0.028) and bleeding G≥1 (61% vs. 34%, p≤0.001). CONCLUSION: Vaginal stenosis represents irreversible fibrotic changes that can cause pain during gynecological examination and dyspareunia in LACC survivors. Regular vaginal dilation (defined as the use of dilators and/or sexual activity) is associated with a significantly lower risk for G≥2 vaginal stenosis, suggesting a potential improvement of vaginal patency. It is also associated with a significantly higher risk for mild G≥1 dryness and bleeding (no higher risk for G≥2), which both can be clinically managed.

Biomarker Expression and Clinical Outcomes in International Study of Chemoradiation and Magnetic Resonance Imaging-Based Image-Guided Brachytherapy for Locally Advanced Cervical Cancer: BIOEMBRACE.

PURPOSE: BIOEMBRACE was designed to study the impact of biomarkers in addition to clinicopathological factors on disease outcomes in patients treated with chemoradiation and magnetic resonance imaging (MRI)-guided brachytherapy (BT) for locally advanced cervical cancer in the EMBRACE study. METHODS AND MATERIALS: Between 2018 and 2021, 8 EMBRACE-I sites contributed tumor tissue for the immunohistochemistry of p16, PD-L1, and L1CAM. These biomarkers and clinicopathological factors (International Federation of Gynecology and Obstetrics 2009 stage, nodal status, histology, and necrosis on MRI) were analyzed to predict poor response at BT (high-risk clinical target volume [HR-CTV] ≥ 40 cc) at BT) and 5-year local control, pelvic control, and disease-free survival. Interaction between p16, PD-L1, radiation therapy dose (HR-CTV D90), and disease outcomes was investigated. Univariable and multivariable analyses were performed. RESULTS: Two hundred sixty-four patients were included. The median HR-CTV D90 was 89 Gy (86-95). P-16 positive status, PD-L1 > 1%, and L1CAM ≥ 10% was noted in 86.6%, 20.1%, and 17.8% of patients, respectively. P16 negative status (odds ratio, 2.0; 95% CI, 1.0-5.7; P = .04) and necrosis on MRI (odds ratio, 2.1; 95% CI, 1.1-4.3; P < .02) independently predicted for HR-CTV ≥ 40 cc, as did the International Federation of Gynecology and Obstetrics stage and tumor width >5 cm. PD-L1 > 1% was associated with reduced local (82% vs 94%; P = .02) and pelvic control (79% vs 89%; P = .02). HR-CTV D90 < 85 Gy was associated with inferior 5-year local control in p16-positive patients, especially if PD-L1 was coexpressed. On multivariable analysis, PD-L1 > 1% was the only independent factor for 5-year local control (hazard ratio, 3.3; P = .04) and L1CAM ≥ 50% for pelvic control (hazard ratio, 5.5; 95% CI, 1.3-23.3; P = .02). CONCLUSIONS: P16 negative status and tumor necrosis on MRI are independently associated with poor response to chemoradiation, whereas PD-L1 > 1% and L1CAM ≥ 50% have an independent impact on local and pelvic control, suggesting an impact of biomarker expression on outcomes. Further validation is needed.

Extramammary Paget's disease of vulva and metastatic adenocarcinoma: A rare conundrum.

Extramammary Paget's disease (EMPD) is a rare intraepithelial adenocarcinoma. To increase awareness and knowledge regarding this rare dermatosis, we hereby reported a case of ulcerated plaque on genitalia.