Neoadjuvant therapy in gynaecological malignancies: What pathologists need to know

In recent times, there has been a growing tendency to treat advanced gynaecological malignancies with neoadjuvant chemotherapy (NACT), with the goal of reducing tumour volume and enhancing operability resulting in optimal cytoreduction. This approach is used in particular for patients with advanced high-grade serous carcinoma of the ovary, fallopian tube or peritoneum. Pathology plays a crucial role in the management of these patients, both before and after NACT. Prior to initiation of NACT, a biopsy should be performed, usually of the omental cake, to confirm that a malignancy is present, to identify the site of origin of the tumour and to type and grade the tumour. Histopathologists must be aware of the resultant morphological effects of NACT when examining specimens following interval cytoreduction surgery. Tumour typing and grading, and even the identification of residual neoplasia, are particular challenges. Immunohistochemistry, when used judiciously, can be a useful adjunct in certain scenarios. A pathological assessment of the response to chemotherapy, and the pathological stage should be provided in the pathology report, as these may inform prognosis and subsequent management. We present a comprehensive overview of the relevant clinical and pathological aspects pertaining to NACT for gynaecological malignancies for the practicing surgical pathologist.

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A randomized phase III, two-arm trial of paclitaxel, carboplatin, and maintenance letrozole versus letrozole monotherapy in patients with stage II-IV, primary low-grade serous carcinoma of the ovary or peritoneum.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.tps5601 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. TPS5601-TPS5601

Author(s):

Amanda Nickles Fader ◽

Lilian Tran Gien ◽

Austin Miller ◽

Al Covens ◽

David Marc Gershenson

Keyword(s):

Clinical Trial ◽

Maintenance Therapy ◽

Aromatase Inhibitor ◽

The United States ◽

Stage Ii ◽

Phase Iii ◽

Serous Carcinoma ◽

Low Grade ◽

Information Time ◽

Carcinoma Of The Ovary

TPS5601 Background: Low-grade serous carcinoma of the ovary or peritoneum (LGSOC) is a rare subtype of epithelial carcinoma. Differences in epidemiology, pathogenesis, disease presentation, and clinical outcomes have been characterized between women diagnosed with LGSOC and those with the p53-driven high-grade serous carcinoma (HGSOC). Ultimately, patients with LGSOC should be treated differently than those with HGSOC. Several studies suggest that LGSOC is relatively chemoresistant and that most tumors robustly express estrogen and progesterone receptors. Recently, retrospective reports suggest that utilization of the aromatase inhibitor, letrozole, as monotherapy or in addition to platinum/taxane-based chemotherapy in those with primary advanced-stage LGSOC results in preliminarily promising survival outcomes. Methods: This study is a two-arm, randomized, open-label, Phase III clinical trial. The primary objective is to assess whether letrozole monotherapy (2.5 mg po daily) is non-inferior to carboplatin (AUC 5-6) and paclitaxel (175 mg/m2) followed by letrozole maintenance therapy with respect to progression free survival in women with primary, Stage II-IV LGSOC who have undergone an attempt at maximal surgical cytoreduction. Secondary endpoints include incidence of adverse events, objective response rate in those with measurable disease after surgery, response duration, overall survival, and adherence to letrozole maintenance therapy. Study subjects must have undergone a bilateral salpingo-oophorectomy, and p53 IHC testing of tumors is required to rule out those with aberrant p53 expression commonly observed in HGSOC tumors. Study strata include residual disease status and country of enrollment. Four hundred and fifty patients will be enrolled in the United States, Canada and South Korea through the NRG Oncology trials network. Correlative aims include analyzing the association of ER/PR tumoral expression with aromatase inhibitor therapy response and determining ESR1 mutational status in those who develop letrozole resistance. The study includes two interim analyses; at 20% information time, a futility analysis will be conducted, and at 40% information time, both efficacy and futility will be assessed. This is one of the first randomized trials performed in women with primary, advanced LGSOC, and the study is open with 71 patients enrolled at the time of abstract submission. Clinical trial information: NCT04095364.

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Stage II to IV Low-grade Serous Carcinoma of the Ovary Is Associated With a Poor Prognosis

International Journal of Gynecological Pathology ◽

10.1097/pgp.0b013e31827630eb ◽

2013 ◽

Vol 32 (6) ◽

pp. 529-535 ◽

Cited By ~ 22

Author(s):

Rola H. Ali ◽

Steve E. Kalloger ◽

Jennifer L. Santos ◽

Kenneth D. Swenerton ◽

C. Blake Gilks

Keyword(s):

Poor Prognosis ◽

Stage Ii ◽

Serous Carcinoma ◽

Low Grade ◽

Carcinoma Of The Ovary

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The Biologic Behavior of Low-Grade Papillary Serous Carcinoma of the Ovary

Obstetrics and Gynecology ◽

10.1097/00006250-200309000-00005 ◽

2003 ◽

Vol 102 (3) ◽

pp. 452

Keyword(s):

Serous Carcinoma ◽

Low Grade ◽

Papillary Serous Carcinoma ◽

Carcinoma Of The Ovary

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The Expression Changes of CX3CL1 and Interlukin-6 Genes During Remission Induction Therapy in Patients With Acute Myeloid Leukemia

Galen Medical Journal ◽

10.31661/gmj.v10i0.2288 ◽

2021 ◽

Vol 10 ◽

pp. e2288

Author(s):

Mahdiyar Iravani Saadi ◽

Mani Ramzi ◽

Aliasghar Karimi ◽

Maryam Owjfard ◽

Mahmoud Torkamani ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Induction Chemotherapy ◽

Induction Therapy ◽

Myeloid Leukemia ◽

Hematologic Malignancy ◽

Quantitative Polymerase Chain Reaction ◽

Remission Induction ◽

Response To Chemotherapy ◽

Before And After ◽

Acute Myeloid

Background: Acute Myeloid Leukemia syndrome (AML) is a hematologic malignancy which is due to clonal extensive proliferation of leukemic precursor cells and is rapidly fatal unless treated or response to chemotherapy. Cytogenetic findings have important role in prognosis and categorization of AML. The aim of this study was to investigate the expression changes in CX3CL1 and Interlukin-6 (IL-6) genes before and after chemotherapy as remission induction therapy in AML patients. Materials and Methods: In this study 69 patients (36 males, 33 female) with AML was selected from tertiary medical heath center. A quantitative polymerase chain reaction (PCR) was done for mRNA expression of CX3CL1 and IL-6genes before and after induction chemotherapy. To obtain expression changes in CX3CL1 and IL-6genes, we used 2-ΔΔCT method. Results: The expression of CX3CL1 and IL-6 was significantly increased after induction chemotherapy. Also, the ΔCt mean of CX3CL1 and IL-6 mRNA was not significant between AML subtype groups. Conclusion: In conclusion, as we showed that chemotherapy significantly increase the expression of CX3CL1 and IL-6 which can be used as a prognostic factor of AML.

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Educational Case: High-Grade Serous Carcinoma of the Ovary

Academic Pathology ◽

10.1177/23742895211032339 ◽

2021 ◽

Vol 8 ◽

pp. 237428952110323

Author(s):

Sophia Bunde ◽

Swikrity Upadhyay Baskota ◽

Jeffrey Fine ◽

Samer Khader

Keyword(s):

Organ System ◽

Learning Objectives ◽

National Standards ◽

Serous Carcinoma ◽

High Grade ◽

Full List ◽

Additional Information ◽

Disease Mechanisms ◽

Basic Competencies ◽

Carcinoma Of The Ovary

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040 .1

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Combination of individual tumor gene expression profiles and quantitative ultrasound and mammography imaging to understand the response to neoadjuvant chemotherapy among Hispanic-Latina women with early stages of triple-negative breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e12605 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e12605-e12605

Author(s):

Alexander Philipovskiy ◽

Sumit Gaur ◽

Karen Chambers ◽

Roberto Gamez ◽

Renato Aguilera ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Neoadjuvant Chemotherapy ◽

Triple Negative ◽

Tumor Response ◽

Residual Disease ◽

Complete Response ◽

Response To Chemotherapy ◽

Before And After ◽

The Individual

e12605 Background: Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer (BC) characterized by the absence of targetable receptors. Traditionally, neoadjuvant chemotherapy (NACT) has been used to downstage the tumors and increase the chance for breast-conserving surgery. The pathological complete response (pCR) has been traditionally considering the best predictive marker for the disease recurrence. Patients with residual disease (RD) have a poor prognosis with a high risk of recurrence, and therefore additional chemotherapy was recommended. Therefore it is an important task for clinical researchers to identify markers to predict the individual tumor response to chemotherapy and avoid in patients potentially resistant tumors. Instead, a surgical approach can be used or combined approach with chemotherapy and immunotherapy. It is not clear yet which approach is optimal for those patients with chemotherapy-resistant tumors since there is no clinical data available and no clinical tool that helps predict the individual tumor response. In this study, we examined breast ultrasound(US) images of patients before and after the completion of NACT and correlated with response to chemotherapy. To better understand the biology of resistance to chemotherapy, we also analyzed the gene expression profile of 15 patients with RD after NACT. Methods: In this study, we retrospective analyzed breast US data from 37 Hispanic patients diagnosed with TNBC and treated with NACT. Patients underwent breast US before and after NACT with documentation of clinical complete response (cCR) or clinical residual disease (cRD). Post-operatively, the pathologic response was defined as the absence of tumor cells (pCR) or presence of residual invasive tumor (RD). A multivariable logistic regression model assessed the influence of patient- and tumor-associated covariates as predictors for pCR. Also, we analyzed formalin-fixed paraffin-embedded tumor samples from 15 patients with RD after NACT. Results: Seventeen patients (45.9%) achieved pCR, and twenty (54.1%) had RD after NACT. The most common US findings connected with RD was the deposition of calcium before NACT six (30%) patients. Gene expression analysis of RD samples identified 446 upregulated and 275 downregulated genes. Among commonly upregulated genes related to cancer, we identified GLI1, IGF1, SERPINE1, ATF3, KLK 5; 7, and TUBB2b, and genes belonging to pathways encoding extracellular matrix–related proteins, DNA-damage response proteins, and pathways related to resistance to chemotherapeutic agents such as Taxol. Conclusions: Our data suggested that gene expression profiling in combination with imaging study can be used to identify patients with TNBC potentially resistant to chemotherapy.

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