Evaluating outcomes and toxicities for a newly implemented MRI-based brachytherapy program for cervical cancer.

OBJECTIVE: We report an updated analysis of the outcomes and toxicities of MRI-based brachytherapy for locally advanced cervical cancer from a U.S. academic center. METHODS: A retrospective review was performed on patients treated with MRI-based brachytherapy for cervical cancer. EBRT was standardly 45 Gy in 25 fractions with weekly cisplatin. MRI was performed with the brachytherapy applicator in situ. Dose specification was most commonly 7 Gy for 4 fractions with optimization aim of D90 HR-CTV EQD2 of 85-95 Gyα/ß=10 Gy in 2 implants each delivering 2 fractions. RESULTS: Ninety-eight patients were included with median follow up of 24.5 months (IQR 11.9-39.8). Stage IIIA-IVB accounted for 31.6% of cases. Dosimetry results include median GTV D98 of 101.0 Gy (IQR 93.3-118.8) and HR-CTV D90 of 89 Gy (IQR 86.1-90.6). Median D2cc bladder, rectum, sigmoid, and bowel doses were 82.1 Gy (IQR 75.9-88.0), 65.9 Gy (IQR 59.6-71.2), 65.1 Gy (IQR 57.7-69.6), and 55 Gy (IQR 48.9-60.9). Chronic grade 3+ toxicities were seen in the bladder (8.2%), rectosigmoid (4.1%), and vagina (1.0%). Three-year LC, PFS, and OS were estimated to be 84%, 61.7%, and 76.1%, respectively. CONCLUSION: MRI-based brachytherapy demonstrates excellent local control and acceptable rates of high-grade morbidity. These results are possible in our population with relatively large volume primary tumors and extensive local disease.

Initial Experience with the Radiotracer 18F-Fluciclovine PET/CT in Ovarian Cancer.

OBJECTIVE: Early and accurate staging of ovarian cancer is paramount to disease survival. Conventional imaging including FDG PET/CT are limited in the evaluation of small metastatic lesions. 18F-Fluciclovine has minimal urine and bowel excretion allowing optimal visualization of the abdomen and pelvis. This study examines 18F-fluciclovine uptake in known primary and recurrent ovarian cancer. METHODS: Seven patients with a confirmed diagnosis of epithelial ovarian cancer underwent 18F-fluciclovine PET/CT imaging. Forty-one (41) lesions were identified with 18F-fluciclovine and confirmed to be true positive (n = 41). We aim to explore if 18F-fluciclovine uptake in ovarian lesions were greater than background uptake of bone marrow, blood pool, and bladder. Quantification analysis was performed to determine max and mean standard uptake values (SUVmax and SUVmean) of known and suspected lesions compared to SUVmean uptake of background structures. RESULTS: 18F-Fluciclovine demonstrated 100% sensitivity (41/41) for uptake in known ovarian lesions. The average SUVmax (±SD) uptake of known ovarian lesions was 5.9 (±2.6) and 5.1 (±2.0) on early and delayed images, respectively. The average tumor SUVmax to SUVmean of background (±SD) (T:B) ratios on early and delay were 1.9 (±0.8), 2.1 (±0.9) for marrow; 3.8 (±1.8), 3.4 (±1.5) for aorta; and 8.4 (±4.3), 1.5 (±1.7) for bladder, respectively. CONCLUSION: 18F-Fluciclovine uptake in malignant ovarian lesions was above background levels suggesting its feasibility in the imaging of ovarian cancer. Due to increasing tracer washout via the urinary bladder over time, early imaging at 4 min post injection is favorable.

Selinexor in Combination with Decitabine Attenuates Ovarian Cancer in Mice.

BACKGROUND: High-grade serous ovarian cancer is a lethal gynecologic disease. Conventional therapies, such as platinum-based chemotherapy, are rendered inadequate for disease management as most advanced disease patients develop resistance to this therapy and soon relapse, leading to poor prognosis. Novel immunotherapy and targeted therapy are currently under investigation as treatment options for ovarian cancer, but so far with little success. Epigenetic changes, such as aberrant DNA methylation, have been reported in resistance to platinum-based therapy. Decitabine is a hypomethylating agent which is effective against platinum-resistant disease and also exhibits several anti-tumor immune functions. Selinexor is a selective inhibitor of nuclear protein export. It restored platinum sensitivity in patient-derived ovarian cancer cell lines and is currently in clinical trials for the treatment of platinum-resistant ovarian cancer. We hypothesized that these two agents used in combination could elicit more potent anti-tumor immune responses in vivo than either agent used alone. METHODS: These studies were designed to investigate the efficacy of these two agents used in combination to treat ovarian cancer by assessing murine models for changes in disease pathology and in anti-tumor responses. RESULTS: Decitabine priming followed by selinexor treatment significantly limited ascites formation and tumor size. This combination of agents also promoted T cell effector function as measured by granzyme B secretion. Treatment of mice with decitabine and selinexor led to the significant release of a broader range of macrophage and T cell cytokines and chemokines above control PBS and vehicle and above decitabine or selinexor treatment alone. CONCLUSIONS: These results reveal crucial information for the design of clinical trials which may advance therapy outcomes in ovarian cancer.

Uterine perforation during brachytherapy for cervical cancer: Complications, outcomes, and best practices for forward treatment planning and management.

PURPOSE: The purpose of the study was to determine the incidence of uterine perforations, review the associated complications, and propose guidelines for management of perforations after brachytherapy. METHODS AND MATERIALS: A retrospective chart review was conducted for all patients with cervical cancer who received single or multiple high-dose-rate brachytherapy implants between April 2006 and May 2017 at a single academic institution. CT and MRI images were retrospectively evaluated to record incidences of uterine perforation of tandem during brachytherapy. Acute and long-term complications during and after treatment were scored using the Common Terminology Criteria for Adverse Events, Version 4.0, of the National Cancer Institute. RESULTS: A total of 123 patients were included in the study. Perforations were observed in 22 patients (17.9%) with 31 (6.4%) of the 482 total implants. Of the different categories of adverse events, only the rate of acute infectious complications among those with perforations (n = 3, 13.6%) versus those without perforations (n = 3, 3.0%) was significant (p = 0.040). Two of the three perforated patients with acute infections had mild urinary tract infections, and all resolved without complications or treatment delays. The remaining one patient had a frank perforation of the anterior uterine wall with a subsequent Grade 3 pyometra infection despite administration of prophylactic antibiotics and 1-week treatment delay. This case was eventually resolved with cervical dilation and evacuation of fluid. Long-term complications were not different between the two arms. CONCLUSIONS: Patients with cervical cancer with uterine perforations may be able to safely proceed with brachytherapy treatment without delay or need for prophylactic antibiotics in the acute setting. Further validating data would be able to assist in establishing a new standard of care and help prevent unnecessary and harmful breaks during treatment.

Repurposing Kir6/SUR2 Channel Activator Minoxidil to Arrests Growth of Gynecologic Cancers.

Gynecologic cancers are among the most lethal cancers found in women, and, advanced stage cancers are still a treatment challenge. Ion channels are known to contribute to cellular homeostasis in all cells and mounting evidence indicates that ion channels could be considered potential therapeutic targets against cancer. Nevertheless, the pharmacologic effect of targeting ion channels in cancer is still understudied. We found that the expression of Kir6.2/SUR2 potassium channel is a potential favorable prognostic factor in gynecologic cancers. Also, pharmacological stimulation of the Kir6.2/SUR2 channel activity with the selective activator molecule minoxidil arrests tumor growth in a xenograft model of ovarian cancer. Investigation on the mechanism linking the Kir6.2/SUR2 to tumor growth revealed that minoxidil alters the metabolic and oxidative state of cancer cells by producing mitochondrial disruption and extensive DNA damage. Consequently, application of minoxidil results in activation of a caspase-3 independent cell death pathway. Our data show that repurposing of FDA approved K+ channel activators may represent a novel, safe adjuvant therapeutic approach to traditional chemotherapy for the treatment of gynecologic cancers.

Salvage treatment in recurrent endometrial cancer of the pelvis and peritoneal cavity.

Regional recurrence of endometrial cancer is a challenging yet potentially curable group of patients without defined standard of care. Our aim is to determine optimal methods of salvage therapy for regionally recurrent endometrial cancer. Twenty-two cases of nodal, pelvic, or peritoneal cavity recurrences of endometrial cancer were identified from a single institution database. Univariable Cox proportional hazards models were used to estimate the risk of a second recurrence or death. Kaplan-Meier plots were used to estimate the probability of progression free survival and overall survival among patients in three cohorts: Multimodality therapy (surgery, chemotherapy, and external beam radiotherapy [EBRT] +/- vaginal brachytherapy), non-surgery (chemotherapy or EBRT, or both), and surgery cohort (surgery +/- chemotherapy OR EBRT). Thirteen recurrences (59%) were regional including the pelvic and paraaortic nodes, while nine recurrences (41%) were abdominal. For the entire cohort, the probability of progression free survival at 2 years was 51% (95% CI, 26% - 72%). The 2-year probability of progression free survival was 62% in the multimodality cohort, 40% in the non-surgery cohort, and 38% in the surgery cohort. The 2-year probability of overall survival was 69% (95% CI, 38% - 86%) across our population. At 40 months of follow up, the only living patients belonged to the multimodality cohort. We found no significant association of a definitive salvage regimen for recurrent endometrial cancer of the pelvis and peritoneal cavity. Aggressive use of multimodality therapy with surgery followed by tumor-directed radiotherapy and chemotherapy offers potentially curative therapy for these patients.

Does adjuvant concurrent or sequential chemotherapy increase the radiation-related toxicity of vaginal brachytherapy for endometrial cancer patients?

PURPOSE: To compare radiation toxicity in endometrial cancer patients treated with adjuvant vaginal brachytherapy (VBT) vs. VBT with concurrent chemotherapy (CCT) or sequential chemotherapy (SCT) METHODS: We retrospectively analyzed 131 patients with endometrial cancer treated with VBT without external beam radiation therapy. Toxicities were graded according to the Common Terminology Criteria for Adverse Events v4.03. CCT was defined as VBT delivered between the first and last cycle of chemotherapy (CT); SCT was defined as VBT delivered before or after CT. RESULTS: Median followup was 36 months, with a 3-year survival rate of 88%. Of the 131 patients, 92 were treated with VBT alone, 34 with VBT and CCT, and 5 with VBT and SCT. The most common toxicity was vaginal stricture, with 30 (22.9%) patients affected. The distribution of toxicities was vaginal 28%, urinary 12%, rectal 11%, and fatigue 5%; none greater than Grade 2. Compared with patients treated with VBT alone, the addition of CT did not increase the chance of vaginal stricture formation (p = 0.84). The difference in system-specific toxicities between treatment modalities was not statistically significant. CONCLUSION: The most common pelvic toxicity from VBT is vaginal stenosis with other toxicities being infrequent and generally Grade 1. The addition of CT in a sequential or concurrent fashion did not increase the rate of pelvic toxicity from VBT alone.

Comparison of dosimetric and clinical outcomes between short- and long-channel cylinder applicators for vaginal brachytherapy in intermediate- and high-risk endometrial cancer.

PURPOSE: Vaginal brachytherapy (VBT) using a cylinder applicator is a standard treatment of intermediate- and high-risk endometrial cancer. We conducted a retrospective study of the dosimetric and clinical outcomes at our institution with 2 single-channel applicators in patients receiving VBT. METHODS AND MATERIALS: One hundred thirty-six patients with endometrial cancer treated from 2006 to 2016 receiving VBT after definitive surgery were evaluated. Two cylinders were used with the distal dwell position 7.1-12.8 mm from the apex varying by diameter (short channel), and 3.2 mm from the apex (long channel). We prescribed 18-26 Gy in 3-4 fractions at 0.5 cm depth. Measurements of the distance from the apex to the prescription isodose line were taken from CT imaging. Student's t test and the Wilcoxon rank-sum test were used with corrections for multiple comparisons. RESULTS: Patients had International Federation of Gynecology and Obstetrics 2009 Stage I-II disease (70 Stage IA, 58 Stage IB, 9 Stage II). Mean cylinder apex dose was 95.2% and 154.7% of prescription (p < 0.001), and mean distance from apex to the prescription isodose line was 0.54 mm and 3.5 mm (p < 0.001) for the short- and long-channel cylinders, respectively. There were no significant differences in any toxicity between cylinders. Four patients (2.9%) had vaginal recurrence, all of whom were treated with the short-channel cylinder. Cylinder type was not associated with vaginal recurrence (p = 0.27). CONCLUSIONS: A cylinder applicator with a distal dwell position closer to the apex results in higher doses to the vaginal cuff and increased D2cc to the bladder. All four recurrences were in the short-channel cylinder. Additional investigation into applicator design and impact on patient outcomes in larger cohorts with sufficient followup is warranted.

Stratification of ovarian tumor pathology by expression of programmed cell death-1 (PD-1) and PD-ligand- 1 (PD-L1) in ovarian cancer.

BACKGROUND: Ovarian cancer is the major cause of death among gynecologic cancers with 75% of patients diagnosed with advanced disease, and only 20% of these patients having a survival duration of five years. Treatments blocking immune checkpoint molecules, programmed cell death (PD-1) or its ligand PD-ligand- I (PD-L1) have produced a beneficial and prolonged effect in a subgroup of these patients. However, there is debate in the literature concerning the prognostic value of the expression of these molecules in tumors, with immunotherapy responsiveness, and survival. We evaluated the immune landscape of the ovarian tumor microenvironment of patients, by measuring the impact of the expression of tumor PD-1, PD-L1 and infiltrating lymphocytes on stage and grade of tumors and survival, in a cohort of 55 patients with gynecologic malignancies. Most patients under study were diagnosed with advanced disease ovarian cancer. RESULTS: Our studies revealed that a low density of PD-1 and of PD-L1 expressing cells in tumor tissue were significantly associated with advanced disease (P = 0.028 and P = 0.033, respectively). Moreover, PD-L1 was expressed significantly more often in high grade tumors (41.5%) than in low grade tumors of patients (7.7%) (P = 0.040). The presence of CD3 or of FoxP3 infiltrating cells with PD-L1 in patient tumors did not impact the significance of the association of PD-L1 with high grade tumors (P = 0.040), and our analyses did not show an association between the presence of PD-1 or PD-L1 and survival. CONCLUSIONS: We conclude that a subgroup of advanced disease ovarian cancer patients with high grade tumors, expressing PD-L1, may be prime candidates for immunotherapy targeting PD-1 signaling.

Adjuvant External Radiation Impacts Outcome of Pelvis-limited Stage III Endometrial Carcinoma: A Multi-institutional Study.

BACKGROUND: Adjuvant therapy choice for women with FIGO stage III endometrial carcinoma (EC) is controversial. We investigate the comparative benefit of adjuvant chemotherapy (CT) alone, radiation therapy alone (RT) or in combination (chemotherapy and radiation therapy [CRT]) with respect to recurrence-free survival (RFS) and overall survival (OS) in women with pelvis-limited (PL) EC (stage IIIA, IIIB, and IIIC1). MATERIALS AND METHODS: A multi-institutional database of 270 surgically staged women with PLEC was analyzed. Univariate log-rank analyses and Cox regression multivariate analyses (MVA) were performed to identify factors associated with RFS and OS. RESULTS: Median RFS and OS were 112 and 130 months, respectively, for the full cohort. Adjuvant treatment was CT in 21%, RT in 27%, and CRT in 47%. Age, year of treatment, grade, histology, and adjuvant treatment were significantly associated with RFS and OS on univariate analysis. PLEC patients receiving CT alone fared worse in terms of RFS (P=0.07 relative to RT and <0.01 relative to CRT). On MVA, CRT retained significantly improved RFS relative to CT (hazard ratio for recurrence 0.38, P<0.01). PLEC patients receiving RT or CRT had improved OS compared with CT, P<0.01 and 0.03, respectively. On MVA, both RT only and CRT retained association with improved OS relative to CT alone (hazard ratio for death, 0.43, P=0.02 and 0.40, P<0.01, respectively). CONCLUSIONS: For surgically staged PL stage III EC, treatment regimens incorporating RT were associated with improved survival endpoints relative to CT alone. As such, RT should be considered an important component in the adjuvant management of stage III PLEC.

Early outcomes and impact of a hybrid IC/IS applicator for a new MRI-based cervical brachytherapy program.

PURPOSE: The purpose of this study was to report early outcomes and assess the learning curve in a new MRI-based cervical brachytherapy program. METHODS: We accrued 33 patients prospectively, and only patients with ≥3 months' followup (n = 27) were assessed for disease control and toxicity. Eras were defined as first half and second half for the intracavitary (IC)-only era (n = 13 each), and the intracavitary/interstitial (IC/IS) era was separated by difference in applicator availability (n = 7). Dose to 90% of the high-risk clinical target volume (D90 HR-CTV) and minimum dose to the maximally irradiated 2 cubic centimeters (D2cc) to organs at risk were used to assess dosimetry. Statistics were performed with t tests and Kaplan-Meier method. RESULTS: Median followup was 14.7 months. Median treatment duration was 50.5 vs. 57 days for patients treated with external beam radiation therapy at our institution vs. an outside institution (p = 0.03). One-year local control, noncervical pelvic control, distant metastasis-free rate, and overall survival were 84.0%, 96.0%, 78.5%, and 91.3%, respectively. When comparing the first half and second half eras of IC only, there were no differences in median D90 HR-CTV or D2cc of the bladder, rectum, or sigmoid. Comparing the entire IC era to the IC/IS era, median D90 HR-CTV trended higher from 88.0 Gy to 92.9 Gy (p = 0.11). D2cc rectum decreased from 69.3 Gy to 62.6 Gy (p = 0.01), and D2cc bladder trended lower from 87.5 Gy to 83.6 Gy (p = 0.09). CONCLUSIONS: There was no significant difference between the first half and second half eras with IC-only MRI-based brachytherapy. Incorporation of an IC/IS applicator generated the greatest dosimetric improvement. Early results of the MRI-based brachytherapy program are favorable.

How one institution overcame the challenges to start an MRI-based brachytherapy program for cervical cancer.

PURPOSE: Adaptive magnetic resonance imaging (MRI)-based brachytherapy results in improved local control and decreased high-grade toxicities compared to historical controls. Incorporating MRI into the workflow of a department can be a major challenge when initiating an MRI-based brachytherapy program. This project aims to describe the goals, challenges, and solutions when initiating an MRI-based cervical cancer brachytherapy program at our institution. MATERIAL AND METHODS: We describe the 6-month multi-disciplinary planning phase to initiate an MRI-based brachytherapy program. We describe the specific challenges that were encountered prior to treating our first patient. RESULTS: We describe the solutions that were realized and executed to solve the challenges that we faced to establish our MRI-based brachytherapy program. We emphasize detailed coordination of care, planning, and communication to make the workflow feasible. We detail the imaging and radiation physics solutions to safely deliver MRI-based brachytherapy. The focus of these efforts is always on the delivery of optimal, state of the art patient care and treatment delivery within the context of our available institutional resources. CONCLUSIONS: Previous publications have supported a transition to MRI-based brachytherapy, and this can be safely and efficiently accomplished as described in this manuscript.

Randomized trial of medroxyprogesterone acetate for the prevention of endometrial pathology from adjuvant tamoxifen for breast cancer: SWOG S9630.

The proliferative effect of adjuvant tamoxifen on the endometrium can potentially result in endometrial abnormalities, including cancer in postmenopausal women. We conducted a randomized, controlled trial to assess endometrial pathological diagnoses in postmenopausal women with early stage, ER-positive breast cancer without endometrial pathology at baseline. They were assigned to tamoxifen alone versus tamoxifen plus cyclical medroxyprogesterone acetate (MPA 10 mg for 14 days every 3 months) for 5 years. Endovaginal sonograms (EVS) +/- endometrial biopsies (EMB) were required at baseline, 2 and 5 years. Of 313 patients registered, 296 were eligible and 169 (57%; 89, tamoxifen; 80, tamoxifen+MPA) were evaluable (completed year-2 EVS, with an EMB if stripe width was ⩾5 mm). Sixty (67%) of these in the tamoxifen arm had an endometrial stripe width ⩾5 mm (and underwent subsequent EMB) compared with 48 (60%) in the tamoxifen+MPA arm (P=0.40). There were four cases of proliferative endometrium and one simple hyperplasia on the tamoxifen arm (6% (95% confidence interval (CI): 2-13%) among evaluable patients and one proliferative endometrium on the tamoxifen+MPA arm (P=0.11). The overall fraction with benign endometrial abnormalities at year 2 was 3.6% (6/169; 95% CI: 1.3-7.6%), with only 1 (of 102) new benign proliferative event at year 5. The event rate in both arms was much lower than projected, making treatment arm comparisons less informative. A normal endometrium prior to tamoxifen may provide reassurance regarding future endometrial events. However, validation in a larger trial is needed before changing practice in asymptomatic, postmenopausal women.

Fatal case of luteinized thecoma with sclerosing peritonitis in a 40-year-old woman.

We describe the pathologic and clinical presentation of a very rare, fatal case of luteinized thecoma with sclerosing peritonitis in a 40-year-old woman, who had a history of total abdominal hysterectomy and a left salpingo-oophorectomy in 2003. The patient presented with abdominal pain, and radiologic examinations revealed a 10-cm heterogenous right pelvic mass with partial necrosis. The patient eventually underwent an exploratory laparotomy, which revealed an ovarian tumor with multiple implants in the peritoneal cavity. The ovarian lesion was made up of spindle cells among clusters of luteinized stromal cells that expanded to the ovarian cortex. Tumor cells were positive for vimentin, estrogen and progesterone receptors, and CCD68 (focally) and negative for CD34, α-smooth muscle actin, ß-catenin, and desmin by immunohistochemical studies. Luteinized cells were positive for α-inhibin and calretinin. Tumor cells exhibited low Ki-67 proliferation indices. The patient died because of the sclerosing peritonitis component of the disease.

Is bilateral lymphadenectomy for midline squamous carcinoma of the vulva always necessary? An analysis from Gynecologic Oncology Group (GOG) 173.

OBJECTIVE: To determine which patients with near midline lesions may safely undergo unilateral groin dissection based on clinical exam and lymphoscintigraphy (LSG) results. METHODS: Patients participating in GOG-173 underwent sentinel lymph node (SLN) localization with blue dye, and radiocolloid with optional LSG before definitive inguinal-femoral lymphadenectomy (LND). This analysis interrogates the reliability of LSG alone relative to primary tumor location in those patients who had an interpretable LSG and at least one SLN identified. Primary tumor location was categorized as lateral (>2cm from midline), midline, or lateral ambiguous (LA) if located within 2cm, but not involving the midline. RESULTS: Two-hundred-thirty-four patients met eligibility criteria. Sixty-four had lateral lesions, and underwent unilateral LND. All patients with LA (N=65) and midline (N=105) tumors underwent bilateral LND. Bilateral drainage by LSG was identified in 14/64 (22%) patients with lateral tumors, 38/65 (58%) with LA tumors and in 73/105 (70%) with midline tumors. At mapping, no SLNs were found in contralateral groins among those patients with LA and midline tumors who had unilateral-only LSGs. However, in these patients groin metastases were found in 4/32 patients with midline tumors undergoing contralateral dissection; none were found in 27 patients with LA tumors. CONCLUSION: The likelihood of detectable bilateral drainage using preoperative LSG decreases as a function of distance from midline. Patients with LA primaries and unilateral drainage on LSG may safely undergo unilateral SLN.

Lymphatic mapping and sentinel lymph node biopsy in women with squamous cell carcinoma of the vulva: a gynecologic oncology group study.

PURPOSE: To determine the safety of sentinel lymph node biopsy as a replacement for inguinal femoral lymphadenectomy in selected women with vulvar cancer. PATIENTS AND METHODS: Eligible women had squamous cell carcinoma, at least 1-mm invasion, and tumor size ≥ 2 cm and ≤ 6 cm. The primary tumor was limited to the vulva, and there were no groin lymph nodes that were clinically suggestive of cancer. All women underwent intraoperative lymphatic mapping, sentinel lymph node biopsy, and inguinal femoral lymphadenectomy. Histologic ultra staging of the sentinel lymph node was prescribed. RESULTS: In all, 452 women underwent the planned procedures, and 418 had at least one sentinel lymph node identified. There were 132 node-positive women, including 11 (8.3%) with false-negative nodes. Twenty-three percent of the true-positive patients were detected by immunohistochemical analysis of the sentinel lymph node. The sensitivity was 91.7% (90% lower confidence bound, 86.7%) and the false-negative predictive value (1-negative predictive value) was 3.7% (90% upper confidence bound, 6.1%). In women with tumor less than 4 cm, the false-negative predictive value was 2.0% (90% upper confidence bound, 4.5%). CONCLUSION: Sentinel lymph node biopsy is a reasonable alternative to inguinal femoral lymphadenectomy in selected women with squamous cell carcinoma of the vulva.

Vaginal cuff dehiscence after intracavitary brachytherapy for endometrial cancer.

We describe 2 unusual cases of vaginal dehiscence after intracavitary brachytherapy performed following robotic laparoscopic hysterectomy (RLH) along with their management. This unusual complication, which may be more common because of the robotic procedures, can be prevented by careful examination and possible delay of the onset of brachytherapy, if indicated. Our report reviews techniques of avoiding this complication and suggests that these complications should be discussed with the patients.

Radiation-related predictors of hematologic toxicity after concurrent chemoradiation for cervical cancer and implications for bone marrow-sparing pelvic IMRT.

PURPOSE: To determine factors predictive for hematologic toxicity (HT) associated with concurrent chemoradiation for Stage II through IV cervical cancer. METHODS AND MATERIALS: The medical records of 40 women receiving concurrent chemoradiation for cervical cancer were reviewed. Hematologic toxicity was defined by use of Common Terminology Criteria for Adverse Events (version 3.0). Variables predicting for HT including age, body mass index, transfusions, and bone marrow volumes irradiated were included in the data analysis. RESULTS: Of the patients, 13 (32.5%) had Grade 0 or 1 HT and 27 (67.5%) had Grade 2 through 4 HT (HT2+). Multiple logistic regression analysis of potential predictors showed that only the volume of bone receiving 20 Gy (V20) for whole pelvic bone tended toward significance for predicting HT2+. A strong correlation was noted between HT2+ and V20 (r = 0.8, p < 0.0001). A partitioning analysis to predict HT2+ showed a cutoff value of 79.42% (approximately 80%) for V20 of whole pelvic bone. That is, if the V20 of the whole pelvis exceeds 80%, the risk of HT2+ developing increases by a factor (odds ratio) of 4.5 (95%, confidence interval, 1.08-18.69) (p < 0.05). CONCLUSIONS: We have shown a correlation between bone marrow volume radiated and development of HT. This has implications for use of pelvic intensity-modulated radiation therapy, which can potentially decrease the volume of bone marrow radiated.

Hepatic resection for recurrent metastatic ovarian cancer.

BACKGROUND: The role for liver resection in metastatic ovarian cancer has not been defined. The aim of the current study was to investigate the validity of hepatic resection as a treatment option in metastatic ovarian cancer. METHODS: Retrospective review of a single institution's experience of patients undergoing hepatic resection for metastatic ovarian cancer from 1998-2006. RESULTS: Ten patients underwent resection for metastatic ovarian cancer. Primary tumor type included serous cystadenocarcinoma (n = 8), granulosa cell (n = 1), and yolk sac (n = 1). Median disease-free interval was 48 months. Liver resections included trisegmentectomy (n = 4), lobectomy (n = 4), and bisegmentectomy(n = 1). Additional surgeries included diaphragm resection (n = 60), bowel resection, (n = 30), and adrenalectomy (n = 10). The median overall survival following liver resection was 33 months. CONCLUSION: Liver resection for metastatic ovarian cancer is safe and is associated with long-term survival in some patients. Larger analysis may lead to the identification of prognostic factors associated with improved outcomes.

FNA diagnosis of retroperitoneal leiomyosarcoma metastasizing to the breast.

Fine-needle aspiration (FNA) biopsy is one of the first-line investigations in any breast lump, and hence cytomorphological recognition of nonmammary metastatic tumors to the breast and their distinction from primary tumors is important. Breast metastasis from extra-mammary malignancy is rare, constituting 2% of breast tumors; even rarer are metastatic leiomyosarcomas. Our patient presented with a breast lump 2 years after operative removal of a retroperitoneal leiomyosarcoma. The breast lump was confirmed to be a metastasis from the earlier primary. Herein, we report the first case of a retroperitoneal leiomyosarcoma metastatic to the breast diagnosed by Fine Needle Aspiration.