MD Anderson Research Highlights: SGO 2022 Spe

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HOUSTON ― The University of Texas MD Anderson Cancer Center Research Highlights provides an insight into current studies in basic, translational, and clinical cancer research by MD Anderson experts. This special issue features oral presentations on women’s cancer by MD Anderson researchers at the 2022 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer, including ovarian cancer genome sequencing, evidence for open radical hysterectomy in cervical cancer, differences in oncofertility, a novel therapeutic target for ovarian cancer and new data on anal human papillomavirus (HPV) infection in women at risk.

Genome sequencing shows improved results in MAPK-mutated tumors

Low-grade serous ovarian/peritoneal carcinoma (LGSOC) is a rare type of ovarian cancer that frequently carries activating mutations in the MAPK signaling pathway, which plays an important role in the pathogenesis of this subtype. Compared to high-grade serous carcinoma, LGSOC is often diagnosed at a younger age in advanced stages and is characterized by prolonged overall survival (OS). In addition, LGSOC is relatively resistant to platinum-based chemotherapy, underscoring the importance of comprehensive genomic analysis to identify novel therapeutic targets and improve the prognosis of these patients.

In a single institute study led by David Gershenson, MD, researchers used next-generation sequencing to analyze the genomic profile of 215 LGSOC patient samples and discover potential associations with clinical outcomes. Most patients had stage III LGSCO and 140 (65%) had one or more mutations in the MAPK pathway, including KRAS, NRAS, BRAF, MAP2K1 and RAF1.

The study found that patients with MAPK-mutated tumors had a significantly longer progression-free survival (PFS) of 31.4 months and OS of 147.8 months compared to patients without mutations, who had a PFS of 23.7 months and OS of 89.5 months. The researchers suggest this underscores the need to develop novel therapies for women with non-MAPK mutant LGSOC.

Minimally invasive surgery continues to show poorer survival for women with cervical cancer

Open radical hysterectomy is the current surgical standard of care for patients with early-stage cervical cancer based on initial results from the Laparoscopic Approach to Cervical Cancer LACC study, led by Pedro Ramirez, MD, which found minimally invasive surgery was associated with four times higher recurrence rates compared to the open approach.

In an updated analysis at a median follow-up of 4.5 years, the results showed that disease-free survival was 96% in patients who underwent open surgery, compared to 85% in patients who underwent minimally invasive surgery . The recurrence rate remained four times higher and overall survival three times worse with the minimally invasive approach.

In an exploratory analysis, the researchers also reported that the recurrence rate was more than four times higher for tumors larger than 2 centimeters with the minimally invasive approach and six times higher for patients without prior cone biopsy. In addition, in patients with recurrence, the metastasis rate after minimally invasive surgery was 24% compared to 0% with open approach.

The results of this study provide further support that open radical hysterectomy should be considered the standard of care in patients with early-stage cervical cancer.

Differences in oncofertility in patients with breast, ovarian, cervical, and endometrial cancer

Therapeutic advances have improved prognosis and survival rates for cancer patients, but current treatments can have adverse effects on patients’ reproductive capacity. Two beneficial approaches are available to preserve fertility, including assisted reproductive technology (ART) – medical treatments or procedures that involve manipulating eggs and sperm to address infertility – and fertility-preserving (FS) oncology care – surgical or medical interventions who preserve the uterus and have at least one ovary for gynecologic cancers. However, the utilization of ART and FS oncology care in women with a history of gynecologic or breast cancer has been understudied in the past.

To better understand rates of ART and FS oncology care, Kirsten Jorgensen, MD, and a team of MD Anderson researchers linked population-level databases to characterize differences in oncofertility. They identified women between the ages of 18 and 45 diagnosed with breast, ovarian, cervical or endometrial cancer and assessed receipt of oncology care from FS and utilization of ART.

They found that ART is underused by women after a breast or gynecological cancer diagnosis. Non-Hispanic Black (NHB) and Hispanic women with a history of breast cancer were less likely to receive ART compared to non-Hispanic White (NHW) women. Conversely, NHB women had a slightly higher likelihood of receiving FS oncology care after a diagnosis of ovarian cancer or endometrial cancer compared to NHW women. Additionally, the researchers found lower rates for both ART use and FS oncology care among rural and uninsured women, regardless of cancer type. Ultimately, more studies are needed to understand these differences given the overall rare results.

Mutations in PPP2R1A may correlate with exceptional survival in ovarian cancer

Immune checkpoint inhibitors (ICIs) offer some patients dramatic and durable disease regression, but response rates in recurrent ovarian cancer have remained low. While new data suggest increased activity in patients with clear cell ovarian cancer (OCCC), only a minority of patients benefit.

Using retrospective and prospective preliminary data from an ongoing clinical study led by Amir Jazaeri, MD, a research team examined biomarkers associated with long-term survival in 28 patients with relapsed, platinum-resistant OCCC treated with anti-CTLA-4 and anti-PD1/L1 ICI. The most common mutant genes identified in the patients were ARID1A (72%), PIK3CA (57%) and PPP2R1A (25%).

patients with PPP2R1A The hotspot mutation achieved a significantly longer OS compared to those without the mutation. Median OS was not reached in seven patients with hotspot inactivation mutations PPP2R1Awhile 21 patients with non-PPP2R1A-mutated OCCC achieved a median overall survival of 6.4 months. Notably, several patients achieved longer-lasting stable disease, resulting in longer survival after initial progression. And in addition, PPP2R1A Mutations were associated with more serious grade 3 or higher immune-related adverse events.

While previous studies have shown that mutation of ARID1A is present in more than 50% of OCCC cases and may be an attractive therapeutic target, preliminary data from this study suggest PPP2R1A Mutations may serve as a better biomarker of ICI’s long-term survival benefit. Researchers are conducting ongoing research to determine the causal link.

Prospective study shows increased prevalence of anal HPV infection in women with cervical, vaginal and vulvar dysplasia or cancer

High-risk human papillomavirus (HR HPV) infection is known to be the most important risk factor for anal cancer and has been associated with more than 90% of all cases. While its role in the development of anal cancer is well established, there is a lack of evidence-based anal cancer screening guidelines for women at risk, including women with HPV-related dysplasia and/or cancer of the lower genital tract, including the cervix, vagina, and vulva.

In a prospective cross-sectional study led by Kathleen Schmeler, MD, researchers analyzed the prevalence of anal dysplasia in 324 women 21 years and older with cervical, vaginal, or vulvar dysplasia or cancer. The primary diagnosis was high-grade dysplasia/cancer of the cervix in 250 patients (77%), followed by vaginal cancer in 28 patients (9%) and vulva in 46 patients (14%).

Results suggested that women with lower genital tract dysplasia or cancer had a high prevalence of HR anal HPV infection and cytological abnormalities. Anal cytology was abnormal in 70 patients (23%), including 56 with atypical squamous cells of undetermined significance (80%), 6 with low-grade squamous intraepithelial lesions (9%), and 1 with high-grade squamous intraepithelial lesion (1%). Anal HR-HPV was detected in 92 patients (28%), while 154 patients (48%) tested positive for cervical/vaginal HR-HPV and 60 patients (36%) tested positive for both anal and cervical/vaginal HR-HPV was proven. In contrast, 32 (19%) had positive anal but negative HR cervical/vaginal HPV, and 76 (45%) had negative anal but positive cervical/vaginal HR HPV.

The higher prevalence of HR anal HPV infection and anal cytologic abnormalities in women with cervical, vaginal, and vulvar malignancies reinforces the need for further studies to determine the rate of progression to high-grade anal dysplasia and cancer and to inform appropriate screening guidelines in this population .

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About MD Anderson

The MD Anderson Cancer Center at the University of Texas at Houston is recognized as one of the world’s most respected centers focused on the care, research, education and prevention of cancer patients. The institution’s sole mission is to end cancer for patients and their families around the world. MD Anderson is one of only 51 comprehensive cancer centers designated by the National Cancer Institute (NCI). MD Anderson is ranked #1 for cancer in US News & World Report’s “Best Hospitals” ranking and has been named one of the top two cancer hospitals in the nation since the ranking began in 1990. MD Anderson receives a grant from NCI for National Institutes of Health Cancer Centers (P30 CA016672).

© 2022 University of Texas MD Anderson Cancer Center


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