Cervical cancer is a malignant epithelial tumor that forms in the uterine cervix. Most cases of cervical cancer are preventable through human papilloma virus (HPV) vaccination, routine screening, and treatment of precancerous lesions. However, due to inadequate screening protocols in many regions of the world, cervical cancer remains the fourth-most common cancer in women globally. The complete NCCN Guidelines for Cervical Cancer provide recommendations for the diagnosis, evaluation, and treatment of cervical cancer. This manuscript discusses guiding principles for the workup, staging, and treatment of early stage and locally advanced cervical cancer, as well as evidence for these recommendations. For recommendations regarding treatment of recurrent or metastatic disease, please see the full guidelines on NCCN.org.
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Wui-Jin Koh, Nadeem R. Abu-Rustum, Sarah Bean, Kristin Bradley, Susana M. Campos, Kathleen R. Cho, Hye Sook Chon, Christina Chu, Rachel Clark, David Cohn, Marta Ann Crispens, Shari Damast, Oliver Dorigo, Patricia J. Eifel, Christine M. Fisher, Peter Frederick, David K. Gaffney, Ernest Han, Warner K. Huh, John R. Lurain III, Andrea Mariani, David Mutch, Christa Nagel, Larissa Nekhlyudov, Amanda Nickles Fader, Steven W. Remmenga, R. Kevin Reynolds, Todd Tillmanns, Stefanie Ueda, Emily Wyse, Catheryn M. Yashar, Nicole R. McMillian and Jillian L. Scavone
Yuefeng Wang, Xinhua Yu, Nan Zhao, Jiajing Wang, Chi Lin, Enrique W. Izaguirre, Michael Farmer, Gary Tian, Bradley Somer, Nilesh Dubal, David L. Schwartz, Matthew T. Ballo and Noam A. VanderWalde
Background: Chemotherapy with or without pelvic radiotherapy (RT) is included in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for metastatic anal cancer (MAC), despite limited clinical evidence for RT in this setting. In addition, increasing evidence shows that local therapies, including RT, may increase patient survival for some types of metastatic cancers. The purpose of this study was to evaluate the patterns of care and association between definitive pelvic RT and overall survival (OS) for patients with MAC. Methods: The National Cancer Database was analyzed to evaluate OS of patients with newly diagnosed MAC treated with chemotherapy with or without pelvic RT. Those who did not undergo treatment, treated with surgery, or without baseline variables were excluded. OS was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score–matched analyses. Results: From 2004 through 2015, 437 patients received chemotherapy alone and 1,020 received pelvic chemoradiotherapy (CRT). At a median follow-up of 17.3 months, CRT was associated with improved OS on univariate (P<.001) and multivariate analysis (hazard ratio [HR], 0.70; 95% CI, 0.61–0.81; P<.001). Propensity score–matched analysis demonstrated superior median survival (21.3 vs 15.9 months) and 2-year OS rates (46% vs 34%) with CRT compared with chemotherapy alone (P<.001). Landmark analyses limited to long-term survivors of ≥1, ≥2, and ≥4 years showed improved OS with CRT in all subsets (all P<.05). CRT with therapeutic doses (≥45 Gy) was associated with longer median survival than palliative doses (<45 Gy) and chemotherapy alone (24.9 vs 10.9 vs 15.6 months, respectively; P<.001). The benefit of CRT was present among not only those with distant lymph node metastasis (HR, 0.63; P=.04) but also those with distant organ disease (HR, 0.74; P<.001). Conclusions: In this large hypothesis-generating analysis, patients with newly diagnosed MAC who received definitive pelvic RT with chemotherapy lived significantly longer than those who received chemotherapy alone. Prospective trials evaluating definitive local RT for MAC are warranted.
Shi-Yi Wang, Tiange Chen, Weixiong Dang, Sarah S. Mougalian, Suzanne B. Evans and Cary P. Gross
Background: Literature suggests that Oncotype DX (ODX) is cost-effective. These studies, however, tend to ignore clinical characteristics and have not incorporated population-based data regarding the distribution of ODX results across different clinical risk groups. Accordingly, this study assessed the cost-effectiveness of ODX across strata of clinical risk groups using population-based ODX data. Methods: We created state-transition models to calculate costs and quality-adjusted life years (QALYs) gained over the lifetime for women with estrogen receptor (ER)–positive, HER2-negative, lymph node–negative breast cancer from a US payer perspective. Using the Connecticut Tumor Registry, we classified the 2,245 patients diagnosed in 2011 through 2013 into 3 clinical risk groups according to the PREDICT model, a risk calculator developed by the National Health Service in the United Kingdom. Within each risk group, we then determined the recurrence score (RS) distributions (<18, 18–30, and ≥31). Other input parameters were derived from the literature. Uncertainty was assessed using deterministic and probabilistic sensitivity analyses. Results: Approximately 82.5%, 11.9%, and 5.6% of our sample were in the PREDICT low-, intermediate-, and high-risk groups, respectively. When combining these 3 groups, ODX had an incremental cost-effectiveness ratio (ICER) of $62,200 per QALY for patients aged 60 years. The ICERs, however, differed across clinical risk groups, ranging from $124,600 per QALY in the low-risk group, to $28,700 per QALY in the intermediate-risk group, to $15,700 per QALY in the high-risk group. Results were sensitive to patient age: the ICER for patients aged 45 to 75 years ranged from $77,100 to $344,600 per QALY in the PREDICT low-risk group, and was lower than $100,000 per QALY in the intermediate- and high-risk groups. Conclusions: ODX is not cost-effective for women with clinical low-risk breast cancer, which constitutes most patients with ER-positive disease.
William G. Wierda, John C. Byrd, Jeremy S. Abramson, Syed F. Bilgrami, Greg Bociek, Danielle Brander, Jennifer Brown, Asher A. Chanan-Khan, Julio C. Chavez, Steve E. Coutre, Randall S. Davis, Christopher D. Fletcher, Brian Hill, Brad S. Kahl, Manali Kamdar, Lawrence D. Kaplan, Nadia Khan, Thomas J. Kipps, Shuo Ma, Sami Malek, Anthony Mato, Claudio Mosse, Vishala T. Neppalli, Mazyar Shadman, Tanya Siddiqi, Deborah Stephens, Nina Wagner, Mary A. Dwyer and Hema Sundar
Chronic lymphocytic leukemia (CLL) is generally characterized by an indolent disease course. Histologic transformation (also known as Richter's transformation) to more aggressive lymphomas, such as diffuse large B-cell lymphoma or Hodgkin lymphoma, occurs in approximately 2% to 10% of patients and is associated with a poor prognosis. These NCCN Guidelines Insights discuss the recommendations for the diagnosis and management of patients with histologic transformation.
Kevin Yauy, Marion Imbert-Bouteille, Virginie Bubien, Clothilde Lindet-Bourgeois, Gauthier Rathat, Helene Perrochia, Gaëtan MacGrogan, Michel Longy, Didier Bessis, Julie Tinat, Stéphanie Baert-Desurmont, Maud Blanluet, Pierre Vande Perre, Karen Baudry, Pascal Pujol and Carole Corsini
Cowden syndrome (CS) is an autosomal dominant mendelian disease related to germline pathogenic variants affecting the PTEN-gene. CS is characterized by macrocephaly, mucocutaneous lesions, and an increased risk of breast and thyroid cancers. Rare ovarian cancer cases (mostly embryonic tumors) associated with PTEN have been described in the literature, but no current CS guidelines are available for ovarian cancer risk management. We report on a woman diagnosed with ovarian clear cell carcinoma (OCCC) at 28 years of age. The patient displayed macrocephaly, trichilemmomas, oral papillomatosis, and acral keratosis. A family history of multiple cancer cases within the PTEN-related tumor spectrum was identified. In addition, PET scan and fine-needle biopsy results led to a diagnosis of thyroid follicular neoplasia. PTEN sequencing revealed that she carried a germline inherited pathogenic variant in exon 5 c.388C>T, p.(Arg130*) (NM_000314). Somatic mismatch repair immunohistochemistry analysis showed normal expression, and germline BRCA1/2 sequencing did not reveal pathogenic or likely pathogenic variants. An ovarian cell immunohistochemistry analysis reported total loss of PTEN expression, which strongly suggested the role of PTEN in the oncogenesis of this cancer. Hence, a total thyroid resection was performed instead of thyroid lobectomy and a risk-reducing bilateral mastectomy was discussed. Co-occurrence of this pathogenic germline mutation in PTEN in this patient, early development of OCCC at age 28 years, and total loss of PTEN expression in the tumor might support the involvement of PTEN in the carcinogenesis of her ovarian cancer. We describe a new ovarian cancer case with an atypical histologic type—clear cell carcinoma—in CS. This observation might be the first indication of the need to expand the PTEN-related tumor spectrum to incorporate OCCC. The CS diagnosis significantly changed the therapeutic outcome of this patient.