Asima Mukhopadhyay

Ovarian cancer

Epithelial ovarian cancer (EOC) describes a group of diseases characterized by differing pathogeneses, molecular profiles, histologies and prognoses. The low incidence of each distinct histological type of EOC poses challenges for obtaining an accurate diagnosis, robust evidence to guide management, and a mechanistic understanding to ensure availability of effective therapies. Most EOCs, including high-grade serous ovarian cancer, predominantly originate from the fimbriated ends of the fallopian tube, whereas low-grade serous, clear cell, endometrioid and mucinous EOCs are thought to originate from other tissues. Despite recognized genetic susceptibilities for the disease, no effective screening is available and late-stage diagnosis remains common. Known genetic susceptibilities are addressed by risk reduction surgery including removal of both fallopian tubes and both ovaries. Management is predominantly based on adequate surgery and chemotherapy with carboplatin and paclitaxel, with the addition of anti-angiogenic therapy as indicated. The incorporation of poly(ADP-ribose) polymerase inhibitors into first-line therapy has considerably altered outcomes in some women with EOC who have defective homologous recombination DNA repair, including in those with BRCA1 and/or BRCA2 mutations. Other molecular characteristics are important in distinct types of EOC, but the use of matched targeted therapies remains under investigation, as does the role of immunotherapy for EOC, for which trial data have been disappointing to date. Translationally enriched clinical trials will be important to further explore and validate accurate biomarkers to better guide clinical care.

Challenges and Opportunities in the Treatment of Invasive Cervical Cancer in Low-Resource Settings: A Survey of the International Gynecologic Cancer Society Fellowship Programs

PURPOSE Cervical cancer remains a leading cause of cancer mortality in low- and middle-income countries (LMICs). The International Gynecologic Cancer Society (IGCS) Global Gynecologic Oncology Fellowship aims to build human capacity to address the burden of cervical cancer in LMICs. This study assesses resource constraints experienced at fellowship sites with regard to management of cervical cancer. METHODS From September to December 2020, one fellow from each of the 12 existing IGCS fellowship programs participated in a survey that assessed capacity for cervical cancer management, including access to care, diagnostics and treatment, cancer surveillance, and palliative care. Descriptive statistics were used for analysis. RESULTS Patients at IGCS sites experienced significant delays to care, especially for chemotherapy and radiation therapy. Less than half of the sites had a gynecology-trained pathologist, and only 58% of sites had access to a magnetic resonance imaging machine, though with many delays in obtaining imaging reads. For treatment, neoadjuvant chemotherapy is not commonly used. Access to radiation therapy is poor, with 58% of sites reporting wait times of 5-8 weeks or more. The radiation machine downtime ranges from 1 to 3 months per year, creating gaps where no patients can access this treatment. Palliative care is practiced by variable members of the health care team although hospice services are rare. CONCLUSION This study demonstrates significant resource constraints experienced by gynecologic oncology providers in various LMICs when managing cervical cancer. This includes delays to diagnosis, poor access to chemoradiation services, and need for palliative care. Despite these limitations, the IGCS Global Gynecologic Oncology Fellowships have built workforce capacity to manage cervical cancer, serving as local champions to address this disease.

Therapeutic effects of surgical debulking of metastatic lymph nodes in cervical cancer IIICr: a trial protocol for a phase III, multicenter, randomized controlled study (KGOG1047/DEBULK trial)

Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, well-planned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m²), 4-6 times administered intravenously. The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. ClinicalTrials.gov Identifier: NCT05421650; Clinical Research Information Service Identifier: KCT0007137.