OVARIO phase II trial of combination niraparib plus bevacizumab maintenance therapy in advanced ovarian cancer following first-line platinum-based chemotherapy with bevacizumab.

OBJECTIVE: To assess safety and efficacy of niraparib + bevacizumab as a first-line maintenance therapy for patients with newly diagnosed advanced ovarian cancer. METHODS: This multicenter, phase II, single-arm, open-label study enrolled adult patients with stage IIIB to IV ovarian, fallopian tube, or primary peritoneal cancer (NCT03326193). Patients were required to have an attempt at debulking surgery and have a complete response, partial response, or no evidence of disease following first-line, platinum-based chemotherapy with ≥3 cycles of bevacizumab. The primary endpoint was the progression-free survival (PFS) rate at 18 months. Secondary endpoints included PFS, overall survival, and safety. RESULTS: Among the 105 evaluable patients, the PFS rate at 18 months was 62% (95% CI 52-71%) in the overall population and 76% (95% CI 61-87) in the homologous recombination deficient (HRd), 47% (95% CI 31-64%) in the HR proficient (HRp), and 56% (95% CI 31-79%) in the HR not determined (HRnd) subgroups (December 24, 2020, cutoff). After a median follow-up time of 28.7 months (IQR, 23.9-32.5 months), median PFS was 19.6 months (95% CI 16.5-25.1) in the overall population (N = 105) and 28.3 months (95% CI 19.9-NE), 14.2 months (95% CI 8.6-16.8), and 12.1 months (95% CI 8.0-NE) in the HRd, HRp, and HRnd subgroups, respectively (June 16, 2021, cutoff). The most common any-grade treatment-related adverse events (related to niraparib and/or bevacizumab) were thrombocytopenia (74/105), fatigue (60/105), and anemia (55/105; December 24, 2020, cutoff). CONCLUSION: Niraparib + bevacizumab first-line maintenance therapy displayed promising PFS results. Safety was consistent with the known safety profiles of niraparib and bevacizumab as monotherapy.

Up-Front Multigene Panel Testing for Cancer Susceptibility in Patients With Newly Diagnosed Endometrial Cancer: A Multicenter Prospective Study.

PURPOSE: Clinical utility of up-front multigene panel testing (MGPT) is directly related to the frequency of pathogenic variants (PVs) in the population screened and how genetic findings can be used to guide treatment decision making and cancer prevention efforts. The benefit of MGPT for many common malignancies remains to be determined. In this study, we evaluated up-front MGPT in unselected patients with endometrial cancer (EC) to determine the frequency of PVs in cancer susceptibility genes. METHODS: Patients with EC were prospectively enrolled at nine Ohio institutions from October 1, 2017, to December 31, 2020. Nine hundred and sixty-one patients with newly diagnosed EC underwent clinical germline MGPT for 47 cancer susceptibility genes. In addition to estimating the prevalence of germline PVs, the number of individuals identified with Lynch syndrome (LS) was compared between MGPT and tumor-based screening. RESULTS: Likely pathogenic variants or PVs were identified in 97 of 961 women (10.1%). LS was diagnosed in 29 of 961 patients (3%; 95% CI, 2.1 to 4.3), with PVs in PMS2 most frequent. MGPT revealed nine patients with LS in addition to the 20 identified through routine tumor-based screening. BRCA1 and BRCA2 PVs were found in 1% (10 of 961; 95% CI, 0.6 to 1.9) of patients and that group was significantly enriched for type II ECs. CONCLUSION: This prospective, multicenter study revealed potentially actionable germline variants in 10% of unselected women with newly diagnosed EC, supporting the use of up-front MGPT for all EC patients. The discovery that BRCA1 or BRCA2 heterozygotes frequently had type II cancers points to therapeutic opportunities for women with aggressive histologic EC subtypes.

Cervical cancer radiation therapy compliance rates based on location of radiation therapy.

OBJECTIVE: Completion of radiation therapy (RT) within 60 days has been proposed as a national quality measure for patients with carcinoma of the cervix as protracted RT has been associated with worse oncologic outcomes. The objective of this study was to compare compliance rates based on location of RT administration. METHODS: This was a retrospective chart review of patients diagnosed with cervical cancer between January of 2000 to December of 2016 who were planned to undergo primary treatment with sensitizing chemotherapy and RT. Patients who completed both external beam radiation therapy (EBRT) and brachytherapy (BT) at the primary institution were compared to patients who completed a portion or all of their RT elsewhere. The primary outcome measured was completion of RT within 60 days. Secondary outcomes included compliance with sensitizing chemotherapy, total radiation dose, recurrence rate, progression free survival (PFS) and overall survival (OS). The groups were compared using standard statistical analysis. RESULTS: This study included 100 patients, 75 of which received all of their RT at the primary institution. These patients were more likely to complete RT within 60 days when compared to patients who underwent RT at different facilities (58.7% vs 24%, respectively; p = 0.005). Patients who underwent all of their RT at the primary institution completed their therapy an average of 16.4 days sooner (75.1 ±â€¯21.3 days versus 58.7 ±â€¯13.2 days; p = 0.001). Overall survival was significantly improved in this group (p = 0.03). CONCLUSION: Women who complete EBRT and BT at different institutions are more likely to have a protracted RT course (>60 days). These patients should be identified at diagnosis and efforts made to coordinate their care to avoid delays in treatment.

The effect of art therapy on the quality of life in patients with a gynecologic cancer receiving chemotherapy.

OBJECTIVES: Most art therapy research has involved patients with malignancies other than gynecologic cancer. The current study aimed to assess the impact of an art therapy intervention on the quality of life (QOL) in patients with gynecologic cancer who were receiving chemotherapy. METHODS: This was a prospective, non-randomized, pilot study. Eligible patients had a primary or recurrent gynecologic malignancy scheduled to be treated with at least 6 cycles of chemotherapy over 18 weeks. The intervention consisted of five sessions of art therapy during the chemotherapy. Patients completed a Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire prior to starting chemotherapy, and again at completion of the fifth session. Differences between the FACT-G scores were examined by paired t-tests. An increase in the mean FACT-G score indicated an improvement in QOL. At each session, the patients completed a separate, supplemental questionnaire to subjectively rate the benefit of the session and to express their experience with the art intervention. RESULTS: Twenty-four patients enrolled. Eight did not complete the study, leaving 16 evaluable patients. The mean FACT-G score pre-chemotherapy was 82.3 (95% CI: 75.5, 89.2), and post-art therapy was 78.6 (95% CI: 71.7, 85.5). The mean change in QOL was -3.7 points (95% CI: -10.7, 3.2, p = 0.270). A supplemental questionnaire indicated that 15 of 16 patients felt that art therapy was beneficial at each session. CONCLUSIONS: FACT-G scores did not significantly change over the course of chemotherapy in patients with gynecologic cancers receiving art therapy. Several published studies have indicated that chemotherapy is associated with a decline in QOL. Our results suggest art therapy may help to prevent or mitigate this decline.

WWP2 and its association with PTEN in endometrial cancer.

We wished to determine if WWP2 gene expression and PTEN protein levels inversely correlate in human endometrial cancer tissues. Fifty-one endometrioid endometrial tumors and five normal endometrial controls were available for analysis. PTEN protein levels were assessed by immunohistochemistry (IHC). WWP2 and PTEN gene expression were quantitated by RT PCR. Clinical and pathologic information was collected by chart review. We found that in tumors with low PTEN protein but normal mRNA expression there were significantly higher levels of WWP2 expression (p = 0.0017). Increased WWP2 expression was not associated with clinical prognostic factors including lymphovascular space invasion, ≥ 50% myometrial invasion, grade, stage or recurrence. WWP2 expression was not different statistically between tumors and normal controls (p = NS). Therefore, in this cohort, tumors with low PTEN protein but normal mRNA expression had elevated levels of WWP2 expression. This suggests that WWP2 may be playing a role in PTEN degradation in endometrial cancer.

Robotic Hysterectomy for Endometrial Cancer in Obese Patients With Comorbidities: Evaluating Postoperative Complications.

OBJECTIVES: The objective of this study is to determine (1) if there is a relationship between increasing body mass index (BMI) and postoperative complications in patients undergoing robotic hysterectomy for endometrial cancer and (2) if there are additional patient characteristics, specifically preoperative comorbidities, which increase the risk of postoperative complication METHODS: A retrospective chart review was conducted on women who underwent a robotic staging surgery for endometrial cancer from 2006 to 2012. Basic demographics and preoperative and postoperative complications were extracted from the medical records. Obesity was divided into 4 categories, and complication rates were compared across these subgroups. Patients were also divided by the number of comorbidities and compared. RESULTS: The cohort included 543 patients. The BMI ranged from 17.3 to 69.5 kg/m. Three hundred eighty patients (70%) were obese (BMI >30 kg.m). One hundred ninety patients (35%) had no comorbidities other than obesity, and 180 patients (33%) had only 1 comorbidity other than obesity (Table 1).Postoperative complications occurred in 102 (18.7%) of the patients. Severe postoperative complications, including intensive care unit admission, reintubation, reoperation, and perioperative death, occurred in 14 patients (2.6%). Of the nonobese patients, 27 (16.5%) had postoperative complications; of the obese patients, 75 (19.7%) had a complication (P = 0.38). In patients with no comorbidities, 16.3% had a complication; 18% of patients with 1 to 2 comorbidities had a complication, and 28% of patients with 3 or more comorbidities had a complication (P = 0.08). CONCLUSIONS: The postoperative complication rate based on BMI or number of comorbidities was not statistically significant, but patients with greater number of comorbidities had an increased rate of postoperative complications. Patients with certain comorbidities, cardiac and renal specifically, had the highest rates of postoperative complications.

Predicting inpatient stay lasting 2 midnights or longer after robotic surgery for endometrial cancer.

OBJECTIVE: To estimate the rate of inpatient stay and the factors predicting inpatient status after robotic surgery for endometrial cancer following the change in the Medicare definition of "inpatient" to include hospitalization spanning 2 midnights. DESIGN: Retrospective chart review (Canadian Task Force classification II-1). SETTING: Academic hospital. PATIENTS: All patients (n = 395) with endometrial cancer who underwent robotic surgical management between 2006 and 2010. INTERVENTION: The outpatient stay group with hospitalization spanning 1 midnight was compared with the inpatient stay group with hospitalization spanning 2 midnights or longer through estimation of the adjusted relative risk (aRR) for various characteristics of interest. RESULTS: Ninety-six of 395 patients (24.3%) stayed at least 2 midnights and thus were deemed inpatients. Clinical factors associated with inpatient stay were increasing age, history of myocardial infarction (aRR, 2.0; 95% confidence interval [CI], 1.0-3.7), surgery start time at or after 12 noon (aRR, 1.7; 95% CI, 1.2-2.4), perioperative blood transfusion (aRR, 3.2; 95% CI, 2.3-4.5), and surgery performed in the year 2010 (aRR, 0.5; 95% CI, 0.3-0.7). Age ≥ 60 years was associated with at least a 2-fold adjusted risk of prolonged hospitalization. Body mass index, other medical comorbidities, operative duration, estimated blood loss, and performance of lymphadenectomy or additional surgical procedures were not identified as significant risk factors. CONCLUSION: Approximately 75% of the patients undergoing robotic surgery for endometrial cancer were discharged as outpatients. Recognition of factors predicting inpatient stay can improve hospital resource allocation and throughput in women undergoing robotic surgery for endometrial cancer.

Reducing readmissions after robotic surgical management of endometrial cancer: a potential for improved quality care.

OBJECTIVE: To describe readmission patterns after robotic surgery for endometrial cancer and identify risk factors for readmission within 90 days of discharge. METHODS: Patients with endometrial cancer who underwent robotic surgical management at an academic institution from 2006 to 2010 were identified. Patient characteristics, intraoperative data, and postoperative complications were analyzed. Student's t-test and Fisher's exact test were used to compare patients readmitted within 90 days to those who were not. RESULTS: Three hundred ninety-five patients were included. Thirty (7.6%) were readmitted within 90 days of surgical discharge. Length of stay greater than one day (40.0% vs. 23.0%, p=0.04) and postoperative complication (63.3% vs. 13.4%, p<0.01) were associated with readmission. The median interval to readmission was 9.5 days and median duration of subsequent hospitalization was 2.5 days. Fever (31.3%) and workup for vaginal drainage (25.0%) were the most common reasons for readmission. Only 2 of the 10 patients readmitted with fever had culture-proven infection, and no patients readmitted for vaginal drainage had a confirmed urinary tract injury. Of the 30 patients readmitted, 5 required a second operation - 3 for vaginal cuff dehiscence and 2 for port site hernia. CONCLUSIONS: Robotic surgery for endometrial cancer was associated with a 7.6% readmission rate. The most common reasons for readmission, fever and evaluation for urinary tract injury, were frequently not associated with severe illness. This supports additional education to consider raising the threshold for readmission by using more widespread outpatient evaluation for the potential complications of robotic endometrial cancer surgery.

Clostridium septicum Sepsis and Colon Carcinoma: Report of 4 Cases.

An association exists between colon carcinoma and Clostridium septicum infection, especially bacteremia. We reviewed retrospectively all positive blood cultures for this organism at a 300-bed general hospital over 4 years. Four of 15 cases were associated with concurrent colon carcinoma. C. septicum infection was the presenting feature of previously undiagnosed large bowel malignancy in three patients. We report this small case series to alert clinicians to the diverse spectrum and diagnostic difficulties of this rare, potentially catastrophic association. Although commonly associated with necrotizing skin or soft tissue infections, this bacterium can present with nonspecific or atypical symptoms. All patients with positive blood cultures for C. septicum, even without clinical suspicion of large bowel malignancy, should undergo colonoscopy to evaluate for colon carcinoma.

Prevalence and patient characteristics associated with CIN 3 in adolescents.

OBJECTIVE: We sought to identify patient characteristics associated with cervical intraepithelial neoplasia (CIN) 3 in adolescents. STUDY DESIGN: A cross-sectional cohort study was done using a colposcopic database. Data collected included demographic and clinical information as well as cytologic and histologic results. Variables associated with CIN 3 in the univariable analysis (P ≤ .10) were included in a multivariable logistic regression model. RESULTS: Of 614 adolescents evaluated, 48 (8%; 95% confidence interval, 6-10%) had CIN 3. No cancers were detected. In the univariable analysis, parity, ≥ 4 lifetime male sexual partners, and a history of sexually transmitted infections were associated with an increased risk of CIN 3. In the final model, only ≥ 4 sexual partners (compared to <4; adjusted odds ratio, 3.66; 95% confidence interval, 1.26-10.61) was significantly associated with the finding of CIN 3. CONCLUSION: CIN 3 was infrequently encountered in adolescents, and those with multiple sexual partners were at increased risk for CIN 3.

The presence of human papillomavirus or p16 in six cases of retroperitoneal carcinoma.

OBJECTIVE: To describe six cases of unknown primary carcinoma of the retroperitoneum that were positive for human papillomavirus (HPV), a surrogate molecular marker for high-risk HPV (p16), or both. METHODS: Using the MD Anderson pathology database, females with confirmed HPV or p16 expression within retroperitoneal carcinomas of unknown primary were identified. Clinical data were collected by retrospective chart review. One pathologist reviewed all histology. Individuals with known primary were excluded. Data regarding individual demographics, presentation, Pap test history, pathology, HPV and p16 positivity, and outcome were analyzed using descriptive statistics. RESULTS: Six individuals were identified. The median age of the individuals was 43.5 years (range 27-54). Three malignancies (50%) were squamous and three (50%) were undifferentiated. Median follow-up was 12 months (range 6-48 months). Two of the six (33%) individuals had remote histories (more than 10 years) of abnormal Pap test results. All had normal gynecologic examination and Pap test results at diagnosis. Four tumors were HPV-positive (66%) and six were p16-positive (100%). All samples that were HPV-positive were also p16-positive. All individuals underwent treatment with chemotherapy, radiation, or both. One individual underwent initial attempt at resection that was unsuccessful. Two individuals are without evidence of disease, two have had progression of disease, and two have died of their disease. CONCLUSION: Pelvic masses of unknown primary may be HPV-related despite normal cervical examinations. LEVEL OF EVIDENCE: III.

A case of Peutz-Jeghers syndrome with breast cancer, bilateral sex cord tumor with annular tubules, and adenoma malignum caused by STK11 gene mutation.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder, and women with this syndrome are at an increased risk of developing intestinal and extraintestinal malignancies including breast and gynecologic malignancies. This case report presents a patient with PJS with a concomitant breast cancer, bilateral stromal tumors with annular tubules of the ovaries, and adenoma malignum of the cervix. CASE: A 43-year-old woman presented with an advanced-stage breast cancer and a pelvic mass. The patient was treated with neoadjuvant chemotherapy followed by laparotomy with a hysterectomy and oophorectomy. Final pathologic examination revealed a concomitant breast cancer with metastasis to the ovaries, bilateral stromal tumors with annular tubules of the ovaries, and adenoma malignum of the cervix. CONCLUSIONS: Patients with PJS are at a high risk for intestinal and extraintestinal malignancies and can present with multiple concomitant malignancies.