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Adolescent and Young Adult Colorectal Cancer

Joleen M. Hubbard and Axel Grothey

Although the overall incidence of colorectal cancer (CRC) in adolescents and young adults (AYAs) is low, it has seen an increase over the past 2 to 3 decades, which contrasts with the trend of decreased incidence in the older population. This phenomenon is conceivably caused by a lack of routine CRC screening in the young population and lifestyle issues, including the obesity epidemic and dietary factors. Hereditary genetic syndromes (eg, familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer syndrome) and known predisposing medical conditions (eg, inflammatory bowel disease) account for only a minority of CRC cases in AYA. Younger patients with CRC commonly present with more advanced disease at diagnosis and exhibit specific molecular and clinical characteristics associated with a distinct biologic phenotype of CRC compared with older individuals. Matched for stage, however, the prognosis of patients with young-onset CRC is similar to or better than that for older patients. A surprising paucity of data exists on outcomes associated with modern systemic cytotoxic and biologic therapy specifically in young patients with CRC. The toxicity pattern of these treatments, however, differs between young and older patients, partly because of the lower rate of pertinent comorbidities in younger adults. Issues regarding surgical management in the setting of hereditary syndromes and fertility preservation while on therapy are of particular importance to the younger patient population. Future studies should seek to increase understanding of the distinct tumor biology of AYA patients with CRC and the consequences of treatment interventions to optimize outcomes for this population.

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Calcium and Magnesium Use for Oxaliplatin-Induced Neuropathy: A Case Study to Assess How Quickly Evidence Translates Into Practice

Deirdre R. Pachman, Kathryn Ruddy, Lindsey R. Sangaralingham, Axel Grothey, Nilay D. Shah, Andreas S. Beutler, Joleen M. Hubbard, and Charles L. Loprinzi

Substantial research efforts have focused on methods of treating and preventing oxaliplatin-associated neuropathy, the dose-limiting toxicity associated with this drug. Administration of intravenous calcium and magnesium (CaMg) before and after oxaliplatin has been the most studied approach to preventing oxaliplatin-induced neuropathy. Although early reports demonstrated potential benefit, subsequent larger trials failed to confirm the efficacy of CaMg in preventing this adverse effect. This article explores how accumulating evidence for and against the use of CaMg for preventing oxaliplatin-induced neuropathy has impacted clinical practice.

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NCCN Guidelines Insights: Rectal Cancer, Version 6.2020

Featured Updates to the NCCN Guidelines

Al B. Benson III, Alan P. Venook, Mahmoud M. Al-Hawary, Mustafa A. Arain, Yi-Jen Chen, Kristen K. Ciombor, Stacey Cohen, Harry S. Cooper, Dustin Deming, Ignacio Garrido-Laguna, Jean L. Grem, Andrew Gunn, Sarah Hoffe, Joleen Hubbard, Steven Hunt, Natalie Kirilcuk, Smitha Krishnamurthi, Wells A. Messersmith, Jeffrey Meyerhardt, Eric D. Miller, Mary F. Mulcahy, Steven Nurkin, Michael J. Overman, Aparna Parikh, Hitendra Patel, Katrina Pedersen, Leonard Saltz, Charles Schneider, David Shibata, John M. Skibber, Constantinos T. Sofocleous, Elena M. Stoffel, Eden Stotsky-Himelfarb, Christopher G. Willett, Alyse Johnson-Chilla, and Lisa A. Gurski

The NCCN Guidelines for Rectal Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with rectal cancer. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines. These updates include clarifying the definition of rectum and differentiating the rectum from the sigmoid colon; the total neoadjuvant therapy approach for localized rectal cancer; and biomarker-targeted therapy for metastatic colorectal cancer, with a focus on new treatment options for patients with BRAF V600E– or HER2 amplification–positive disease.

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NCCN Guidelines® Insights: Older Adult Oncology, Version 1.2021

Featured Updates to the NCCN Guidelines

Efrat Dotan, Louise C. Walter, Ilene S. Browner, Katherine Clifton, Harvey Jay Cohen, Martine Extermann, Cary Gross, Sumati Gupta, Genevieve Hollis, Joleen Hubbard, Reshma Jagsi, Nancy L. Keating, Elizabeth Kessler, Thuy Koll, Beatriz Korc-Grodzicki, June M. McKoy, Sumi Misra, Dominic Moon, Tracey O’Connor, Cynthia Owusu, Ashley Rosko, Marcia Russell, Mina Sedrak, Fareeha Siddiqui, Amy Stella, Derek L. Stirewalt, Ishwaria M. Subbiah, William P. Tew, Grant R. Williams, Liz Hollinger, Giby V. George, and Hema Sundar

The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.

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NCCN Guidelines Insights: Older Adult Oncology, Version 2.2016

Noam VanderWalde, Reshma Jagsi, Efrat Dotan, Joel Baumgartner, Ilene S. Browner, Peggy Burhenn, Harvey Jay Cohen, Barish H. Edil, Beatrice Edwards, Martine Extermann, Apar Kishor P. Ganti, Cary Gross, Joleen Hubbard, Nancy L. Keating, Beatriz Korc-Grodzicki, June M. McKoy, Bruno C. Medeiros, Ewa Mrozek, Tracey O'Connor, Hope S. Rugo, Randall W. Rupper, Dale Shepard, Rebecca A. Silliman, Derek L. Stirewalt, William P. Tew, Louise C. Walter, Tanya Wildes, Mary Anne Bergman, Hema Sundar, and Arti Hurria

Cancer is the leading cause of death in older adults aged 60 to 79 years. Older patients with good performance status are able to tolerate commonly used treatment modalities as well as younger patients, particularly when adequate supportive care is provided. For older patients who are able to tolerate curative treatment, options include surgery, radiation therapy (RT), chemotherapy, and targeted therapies. RT can be highly effective and well tolerated in carefully selected patients, and advanced age alone should not preclude the use of RT in older patients with cancer. Judicious application of advanced RT techniques that facilitate normal tissue sparing and reduce RT doses to organs at risk are important for all patients, and may help to assuage concerns about the risks of RT in older adults. These NCCN Guidelines Insights focus on the recent updates to the 2016 NCCN Guidelines for Older Adult Oncology specific to the use of RT in the management of older adults with cancer.

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Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

Al B. Benson III, Alan P. Venook, Mahmoud M. Al-Hawary, Mustafa A. Arain, Yi-Jen Chen, Kristen K. Ciombor, Stacey Cohen, Harry S. Cooper, Dustin Deming, Linda Farkas, Ignacio Garrido-Laguna, Jean L. Grem, Andrew Gunn, J. Randolph Hecht, Sarah Hoffe, Joleen Hubbard, Steven Hunt, Kimberly L. Johung, Natalie Kirilcuk, Smitha Krishnamurthi, Wells A. Messersmith, Jeffrey Meyerhardt, Eric D. Miller, Mary F. Mulcahy, Steven Nurkin, Michael J. Overman, Aparna Parikh, Hitendra Patel, Katrina Pedersen, Leonard Saltz, Charles Schneider, David Shibata, John M. Skibber, Constantinos T. Sofocleous, Elena M. Stoffel, Eden Stotsky-Himelfarb, Christopher G. Willett, Kristina M. Gregory, and Lisa A. Gurski

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section. These updates include recommendations for first-line use of checkpoint inhibitors for mCRC, that is deficient mismatch repair/microsatellite instability-high, recommendations related to the use of biosimilars, and expanded recommendations for biomarker testing. The systemic therapy recommendations now include targeted therapy options for patients with mCRC that is HER2-amplified, or BRAF V600E mutation–positive. Treatment and management of nonmetastatic or resectable/ablatable metastatic disease are discussed in the complete version of the NCCN Guidelines for Colon Cancer available at NCCN.org. Additional topics covered in the complete version include risk assessment, staging, pathology, posttreatment surveillance, and survivorship.

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Small Bowel Adenocarcinoma, Version 1.2020, NCCN Clinical Practice Guidelines in Oncology

Al B. Benson III, Alan P. Venook, Mahmoud M. Al-Hawary, Mustafa A. Arain, Yi-Jen Chen, Kristen K. Ciombor, Stacey A. Cohen, Harry S. Cooper, Dustin A. Deming, Ignacio Garrido-Laguna, Jean L. Grem, Sarah E. Hoffe, Joleen Hubbard, Steven Hunt, Ahmed Kamel, Natalie Kirilcuk, Smitha Krishnamurthi, Wells A. Messersmith, Jeffrey Meyerhardt, Eric D. Miller, Mary F. Mulcahy, Steven Nurkin, Michael J. Overman, Aparna Parikh, Hitendra Patel, Katrina S. Pedersen, Leonard B. Saltz, Charles Schneider, David Shibata, John M. Skibber, Constantinos T. Sofocleous, Elena M. Stoffel, Eden Stotsky-Himelfarb, Christopher G. Willett, Alyse Johnson-Chilla, Kristina M. Gregory, and Lisa A. Gurski

Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract that has increased in incidence across recent years. Often diagnosed at an advanced stage, outcomes for SBA are worse on average than for other related malignancies, including colorectal cancer. Due to the rarity of this disease, few studies have been done to direct optimal treatment, although recent data have shown that SBA responds to treatment differently than colorectal cancer, necessitating a separate approach to treatment. The NCCN Guidelines for Small Bowel Adenocarcinoma were created to establish an evidence-based standard of care for patients with SBA. These guidelines provide recommendations on the workup of suspected SBA, primary treatment options, adjuvant treatment, surveillance, and systemic therapy for metastatic disease. Additionally, principles of imaging and endoscopy, pathologic review, surgery, radiation therapy, and survivorship are described.

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Rectal Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology

Al B. Benson III, Alan P. Venook, Mahmoud M. Al-Hawary, Nilofer Azad, Yi-Jen Chen, Kristen K. Ciombor, Stacey Cohen, Harry S. Cooper, Dustin Deming, Ignacio Garrido-Laguna, Jean L. Grem, Andrew Gunn, J. Randolph Hecht, Sarah Hoffe, Joleen Hubbard, Steven Hunt, William Jeck, Kimberly L. Johung, Natalie Kirilcuk, Smitha Krishnamurthi, Jennifer K. Maratt, Wells A. Messersmith, Jeffrey Meyerhardt, Eric D. Miller, Mary F. Mulcahy, Steven Nurkin, Michael J. Overman, Aparna Parikh, Hitendra Patel, Katrina Pedersen, Leonard Saltz, Charles Schneider, David Shibata, John M. Skibber, Constantinos T. Sofocleous, Eden Stotsky-Himelfarb, Anna Tavakkoli, Christopher G. Willett, Kristina Gregory, and Lisa Gurski

This selection from the NCCN Guidelines for Rectal Cancer focuses on management of malignant polyps and resectable nonmetastatic rectal cancer because important updates have been made to these guidelines. These recent updates include redrawing the algorithms for stage II and III disease to reflect new data supporting the increasingly prominent role of total neoadjuvant therapy, expanded recommendations for short-course radiation therapy techniques, and new recommendations for a “watch-and-wait” nonoperative management technique for patients with cancer that shows a complete response to neoadjuvant therapy. The complete version of the NCCN Guidelines for Rectal Cancer, available online at NCCN.org, covers additional topics including risk assessment, pathology and staging, management of metastatic disease, posttreatment surveillance, treatment of recurrent disease, and survivorship.

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Anal Carcinoma, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology

Al B. Benson III, Alan P. Venook, Mahmoud M. Al-Hawary, Nilofer Azad, Yi-Jen Chen, Kristen K. Ciombor, Stacey Cohen, Harry S. Cooper, Dustin Deming, Ignacio Garrido-Laguna, Jean L. Grem, J. Randolph Hecht, Sarah Hoffe, Joleen Hubbard, Steven Hunt, Hisham Hussan, William Jeck, Kimberly L. Johung, Nora Joseph, Natalie Kirilcuk, Smitha Krishnamurthi, Jennifer Maratt, Wells A. Messersmith, Jeffrey Meyerhardt, Eric D. Miller, Mary F. Mulcahy, Steven Nurkin, Michael J. Overman, Aparna Parikh, Hitendra Patel, Katrina Pedersen, Leonard Saltz, Charles Schneider, David Shibata, John M. Skibber, Constantinos T. Sofocleous, Eden Stotsky-Himelfarb, Anna Tavakkoli, Christopher G. Willett, Grant Williams, Frankie Algieri, Lisa Gurski, and Katie Stehman

This discussion summarizes the NCCN Clinical Practice Guidelines for managing squamous cell anal carcinoma, which represents the most common histologic form of the disease. A multidisciplinary approach including physicians from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology is necessary. Primary treatment of perianal cancer and anal canal cancer are similar and include chemoradiation in most cases. Follow-up clinical evaluations are recommended for all patients with anal carcinoma because additional curative-intent treatment is possible. Biopsy-proven evidence of locally recurrent or persistent disease after primary treatment may require surgical treatment. Systemic therapy is generally recommended for extrapelvic metastatic disease. Recent updates to the NCCN Guidelines for Anal Carcinoma include staging classification updates based on the 9th edition of the AJCC Staging System and updates to the systemic therapy recommendations based on new data that better define optimal treatment of patients with metastatic anal carcinoma.