Faculty Bibliography

Objective: The Gynecologic Oncology Group (GOG) study 240 demonstrated a 3.5-month improvement in overall survival when bevacizumab (bev) was added to a combination chemotherapy regimen. This study established a bev-containing regimen as standard therapy for women with recurrent, persistent, or metastatic cervical cancer (CC). Gastrointestinal fistula (GIF) formation is a known complication of bev, and the long-term data of GOG 240 reported that a GIF rate of 15% in women who were treated with bev compared to 1% in the control group women. We sought to evaluate our experience with women treated with bev for CC and to identify associated risk factors for GIF formation.
Method(s): All patients who have received bev for CC from 2012 to 2018 at two academic institutions were identified, and their records were reviewed. Standard two-sided statistical analyses were performed.
Result(s): A total of 43 women were treated with a bev-containing chemotherapy regimen; among them, 34 (79.1%) were treated for CC recurrence, and the remaining were treated for metastatic disease at initial presentation or persistent disease following primary treatment. Thirty-three women (76.6%) received prior radiation therapy (RT); of these, 10 (32.3%) received external beam radiation therapy (EBRT), and 21 (67.7%) had prior EBRT and brachytherapy (BT). The median dose of bev was 15 mg/kg for both EBRT only and EBRT and BT groups. Eleven women developed GIF after bev treatment (11/43, 25.6%). All 11 (100%) had been previously treated with RT, and six (54.5%) had received EBRT plus BT. This resulted in rates of 33.3% (11/33) for GIF formation among women who received EBRT, and 28.6% (6/21) for GIF formation among women who received EBRT plus BT. The median number of bev cycles prior to GIF development was 8 (1-29), and 7 (7/11, 63.6%) received the dose of bev (15 mg/kg) as prescribed in GOG 240. See Table 1.
Conclusion(s): In our cohort of women with CC who were treated with bev, over 25% developed GIF. This is more than expected based on the 15% seen in GOG 240. Notably almost all who developed GIF had recurrent disease and were treated with prior RT. A third of women treated with RT followed by bev formed GIF, representing a considerable proportion of the cohort. GIF development and the possibility of requiring a colostomy should be a part of counseling prior to bev initiation especially in those who have had prior RT. [Figure presented]
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Objective: The use of medical marijuana (MM) in cancer patients was legalized in New York state in 2016. Reported benefits of MM include reduction of cancer-associated pain, nausea, vomiting, fatigue, and improved appetite, as well as mitigating other side effects of cancer treatment. Tetrahydrocannabinol (THC) and cannabidiol (CBD), both components of MM, have been shown to have therapeutic benefit for cancer-related symptoms. Dosing of MM is described in terms of the THC:CBD ratio. While the general therapeutic benefits have been documented, there is a paucity of data on MM use in patients with gynecologic cancers (GC). We sought to evaluate the effect of medical marijuana for symptom management in patients with GC at our institution.
Method(s): We retrospectively identified women with GC using MM between May 2016 and August 2018 from the medical record. Demographic data, cancer diagnosis, dosage form, quantity, frequency, length of treatment, indication, and reported efficacy of MM were collected.
Result(s): We identified 34 patients using MM for a diagnosis of GC. Table 1 lists the patient characteristics and indications for MM and dosing. Median age of patients using MM was 60 years (46-78 years). Median length of treatment with MM was 189 days (11-761 days). Response to MM included 17(50%) improvement in symptoms; 3 (9%) minimal change; 10 (29%) not reported yet; and 4 (12%) unknown. Overall, among patients for whom symptom improvement was available to date, 17/20 (85%) noted improvement. Four (12%) patients reported unwanted side effects, which were euphoria, dizziness, fatigue, and paranoia. Three patients who reported side effects received MM with a 1:1 THC:CBD ratio; the other patient received a low THC:high CBD dosing. Only one (3%) patient ceased medical marijuana use because of untoward adverse effects. All the patients who reported an improvement in symptoms while using MM were concurrently receiving chemotherapy. Improvement in symptoms was not related to formulation, form, or length of treatment of MM.
Conclusion(s): An improvement in symptoms associated with cancer and treatment was noted in over 80% of GC patients using MM, and very few reported adverse side effects. MM is likely to be a promising treatment for pain, nausea, and anorexia in GC patients and should be considered in the armamentarium of palliative cancer treatment options. [Figure presented]
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OBJECTIVES/OBJECTIVE:Lynch syndrome (LS) accounts for the majority of inherited endometrial cancers (EC), and the identification of probands presents a unique opportunity to treat and prevent multiple cancers. The diagnosis of EC can provide the indication for women with specific risk factors to undergo genetic testing (GT). We sought to evaluate genetic counseling referrals (GCR) and subsequent GT rates in an ethnically diverse group of high-risk women. METHODS:All women diagnosed with EC between 2011 and 2016 were identified. Risk factors for LS including age, family and personal histories of Lynch-related cancers and loss of tumor mismatch repair (MMR) protein expression were identified from laboratory and medical records. Standard two-sided statistical tests were used. RESULTS:Of 583 women diagnosed with EC, 184 (31.6%) were found to have at least one high-risk characteristic for LS. Among these high-risk women, 58% were given GCR and resulting in only 35% undergoing GT. Ten of the 65 high-risk women who had GT (15.4%) were diagnosed with Lynch syndrome, and all ten met high-risk criteria. Two women of Asian race had tumors exhibiting retained MMR protein expression despite germline testing demonstrating Lynch syndrome. CONCLUSIONS:Many high-risk women do not receive GCR despite a high rate of germline mutations among these women. Improving GCR among high-risk women will lead to more subsequent GT to identify more Lynch syndrome families and prevent additional cancers. Among our ethnically diverse cohort, two women diagnosed with LS had retained MMR protein expression. GCR should be offered to women who possess high-risk characteristics despite normal MMR protein expression.

OBJECTIVES/OBJECTIVE:Black race has been associated with increased 30-day morbidity and mortality following surgery for endometrial cancer. Black women are also less likely to undergo laparoscopy when compared to white women. With the development of improved laparoscopic techniques and equipment, including the robotic platform, we sought to evaluate whether there has been a change in surgical approach for black women, and in turn, improvement in perioperative outcomes. METHODS:Using the American College of Surgeons' National Surgical Quality Improvement Project's database, patients who underwent hysterectomy for endometrial cancer from 2010 to 2015 were identified. Comparative analyses stratified by race and hysterectomy approach were performed to assess the relationship between race and perioperative outcomes. RESULTS:A total of 17,692 patients were identified: of these, 13,720 (77.5%) were white and 1553 (8.8%) were black. Black women were less likely to undergo laparoscopic hysterectomy compared to white women (49.3% vs 71.3%, p<0.0001). Rates of laparoscopy in both races increased over the 6-year period; however these consistently remained lower in black women each year. Black women had higher 30-day postoperative complication rates compared to white women (22.5% vs 13.6%, p<0.0001). When laparoscopic hysterectomies were isolated, there was no difference in postoperative complication rates between black and white women (9.2% vs 7.5%, p=0.1). CONCLUSIONS:Overall black women incur more postoperative complications compared to white women undergoing hysterectomy for endometrial cancer. However, laparoscopy may mitigate this disparity. Efforts should be made to maximize the utilization of minimally invasive surgery for the surgical management of endometrial cancer.

Aims It's recommended that all women with OC undergo genetic counseling (GC) and consider testing (GT). Universal referral was endorsed by SGO in 2014. However, rates of referral to GC are 15-30%. Since 10/2015, women newly diagnosed at our institution have been offered GC through a facilitated referral pathway (FRP). Our objective is to examine differences in GC and GT since implementation of FRP. Method Patients with new diagnosis of OC were retrospectively evaluated from 2012-9/2015 and prospectively since. Through FRP, patients are contacted by a genetics-navigator to schedule GC and communication between patient, physician and genetic counselor are facilitated. Chi-square and Mann-Whitney tests were used. Results There were 216 women diagnosed with OC who hadn't undergone previous GT identified between 2/2012-10/2016, of which 61 (28%) were in FRP and 154 (72%) weren't. Patients in the FRP were significantly more likely to obtain GC than non-FRP patients, and similarly, GT was obtained more often in the FRP group. There were 10 (21%) patients in the FRP and 21 (23%) in the non-FRP group found to have at least one deleterious mutation (p=0.98). Conclusion Implementation of FRP has resulted in a significant increase in GT, with a rate >80% among women with newly diagnosed OC with similar mutation rates in both groups. Although historically uptake of GT has been low, this study highlights the effectiveness of FRP. The implications of increased GT are profound; targeted therapies are now FDA-approved for BRCA1/2 mutation carriers. GT can result in increased screening/risk-reducing measures and allows for cascade testing

Background: Lynch syndrome (LS) accounts for 2-6% of all endometrial cancers (EC), and women with a germline mutation in the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) have an average lifetime risk of EC of 40%. As with breast and ovarian cancer syndromes, there are likely other genes implicated in the development of EC outside of the MMR genes. Multi-gene panel testing (MGPT) with next generation sequencing (NGS) allows for simultaneous analysis of numerous genes.We sought to evaluate the characteristics and incidence of gene mutations in women with newly diagnosed EC. Methods: We conducted a review of EC patients diagnosed from 6/2013 to 12/2016 who had MGPT at our institution. Demographics, family history, genetic testing results, and tumor characteristics were collected and analyzed using chi tests. Results: Of the 129 patients who had MGPT, 13 (10%) had a mutation and only 5 (38%) were in patients < 50 years old. The median age of EC diagnosis is 55 (31-100) years and median BMI = 27.5 (21-59). Majority were stage 1, 76 (59%) and grade 1, 50 (39%). Patients with additional primary cancers, breast or colon were not more likely to have a mutation. However, patients with a family history of gynecologic cancer were more likely to have a mutation identified, 10 (77%) mutation vs no mutation 34 (29%), p = 0.003. Among all patients tested, 8 (6%) had a mutation in LS genes, and 6 (5%) had mutations in other genes (BRCA1, BRCA2, RAD51C, MUTYH, CHEK2); 1 (0.8%) had both MSH2 and CHEK2 mutation. Three patients had prior testing for breast cancer; 2 were found to have a BRCA1/ 2 mutation and the other was on Tamoxifen and BRCA negative. IHC was performed on 7 of 13 patients, and 5 (71%) had a loss of MMR protein expression. Variants of uncertain significance were noted in 35/129 (27%) of patients tested. Conclusions: Majority of EC patients with a mutation detected with NGS were > age 50. We identified additional new mutations in non-LS genes including, CHEK2, RAD51C, and MUYTH with MGPT. These accounted for 29% of the mutations and would have not been not detected using classic LS gene testing. These genes are implicated in breast, ovary or colon cancer. MGPT testing is feasible and useful in identifying additional actionable gene mutations

OBJECTIVE: To assess the availability and capacity of US-based integrated centers for the management of Lynch syndrome. METHODS: A cross-sectional survey of practice patterns in the care of patients with Lynch syndrome was conducted at 33 National Cancer Institute-designated cancer centers in the USA from March 1 to June 1, 2013. Each cancer center was contacted by telephone and the caller used a uniform scripted greeting and survey format. RESULTS: All centers routinely recommended colonoscopy. Other recommended screening modalities were hysterectomy and bilateral salpingo-oophorectomy (29/33; 88%), endoscopy (27/33; 82%), urinalysis (23/33; 70%), endometrial sampling (21/33; 64%), dermatologic examination (19/32; 59%), pelvic ultrasonography (18/33; 55%), serum CA125 level (14/33; 42%), urine cytology (14/33; 42%), computed tomography (1/33; 3%), and magnetic resonance imaging (1/33; 3%). Each center had a multidisciplinary team but the composition varied. A designated team leader was present at 21 centers (64%). Having a team leader was associated with an increased likelihood of recommending endoscopy (P=0.04) and dermatologic surveillance (P=0.01). Only 23 centers (70%) had a system in place for communicating follow-up with patients. CONCLUSION: The lack of consensus in practice patterns recorded among participating centers probably reflected the limited existing evidence on the usefulness of most screening modalities.

OBJECTIVE: To investigate the effect of methotrexate (MTX) or salpingectomy for ectopic pregnancy on the outcomes of subsequent in vitro fertilization (IVF)-embryo transfer (ET) cycles. DESIGN: Retrospective cohort study (Canadian Task Force Classification II-3). SETTING: Academic center. PATIENTS: All patients undergoing fresh IVF-ET between January 2004 and July 2013 after treatment of an ectopic pregnancy with MTX or salpingectomy in the preceding IVF-ET cycle were analyzed for potential inclusion. INTERVENTION: MTX or laparoscopic salpingectomy for an ectopic pregnancy followed by a subsequent IVF-ET cycle. MEASUREMENTS AND MAIN RESULTS: A total of 144 patients with sonographically confirmed ectopic pregnancies were identified during the study period. Of these, 107 (74.3%) patients were treated with MTX and 37 (25.7%) were treated with laparoscopic salpingectomy. Eighty-eight patients (82.2%) in the MTX group and 22 patients (59.4%) patients in the salpingectomy group underwent a subsequent IVF-ET cycle. There were no significant differences in demographic data or baseline cycle characteristics between the 2 groups. No difference was observed in basal follicle-stimulating hormone (FSH) level before and after MTX or salpingectomy treatment. Indicators of ovarian responsiveness, including total days of stimulation, total dosage of gonadotropins, and number of mature oocytes before and after either treatment, were comparable in the 2 groups. The number of doses of MTX (1 vs > 1) did not correlate with changes in ovarian response. The pregnancy outcomes, specifically live birth, were equivalent in the 2 groups. Comparing post-MTX cycles and post-salpingectomy cycles, patients in the latter group required higher doses of gonadotropins (+705 IU vs +221.5 IU; p < .01), although the number of mature oocytes remained similar in the 2 groups. CONCLUSION: Treatment of ectopic pregnancies with MTX or salpingectomy might not adversely affect ovarian reserve, ovarian responsiveness, or subsequent IVF cycle outcomes. However, in our study cohort, patients treated with MTX, those s treated with laparoscopic salpingectomy required higher gonadotropin doses in a subsequent cycle to attain the same number of mature oocytes.

BACKGROUND: Anaplastic large cell lymphoma is rarely diagnosed during pregnancy, and patients may be erroneously diagnosed with a dermatosis. CASE: A 34-year-old female was diagnosed with pruritic urticarial papules and plaques of pregnancy in the third trimester. She underwent elective repeat cesarean section with a postoperative course complicated by skin and gingival ulcers and persistent fever. Imaging revealed lung and brain nodules. Video-assisted thoracic surgery lung biopsy demonstrated anaplastic large cell lymphoma. CONCLUSION: It is important to consider the diagnosis of anaplastic large cell lymphoma in a pregnant patient who presents with cutaneous symptoms.

*Splenosis is a rare complication of splenic trauma or splenectomy.*Splenosis can be mistaken for gynecologic malignancy.*Splenosis must be considered as a diagnosis in all patients with history of prior trauma or splenectomy.