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agree with his contention that treatment decisions cannot be
based solely on molecular data without considering clinical
context. In fact, in our review, we clearly state that despite
improvements in molecular prognostication in CLL, indications to initiate therapy remain based on the International
Working Group Criteria (IW-CLL) that rely heavily on clinical
presentation, disease burden, and stage, without molecular
data.1 Having said that, we believe that this is an evolving
process that is likely to change in the years ahead. In the era
of precision medicine, targeted therapies, and better understanding of the underlying disease biology, it would be critical to tailor intervention to the underlying biological process
that might have led to disease development. Yavorkovsky
specifically discusses 17p13.1 deletion, stating that the presence of this deletion does not necessarily predict poor prognosis. Actually, in our review, we cited the same reference
that Yavorkovsky cites and suggested that some patients
with 17p13.1 deletion could potentially enjoy an indolent
course.2 Furthermore, we emphasized that the presence of
this deletion should not lead to treatment initiation in the
absence of any of the aforementioned IW-CLL criteria. However, these patients should be closely monitored because
they might have increased risk of early disease progression.
Moreover, as new therapies such as ibrutinib, idelalisib, and
venetoclax have demonstrated significant activity in 17p13.1deleted patients,3 clinical trials are now ongoing to explore
whether early initiation of treatment in asymptomatic
patients with this deletion is warranted. We clearly stated
that none of the regulatory bodies recommend early treatment initiation outside the context of clinical trials. We agree
with Yavorkovsky that guidelines should simply be suggestions on how best to approach a disease and should never
replace clinical judgment and experience. While Yavorkovsky suggests that European recommendations that advocate against molecular testing are welcome, we propose that
these recommendations were generated in an era in which
treatments that target higher-risk disease molecularly were
not available. Molecular testing not only aids in a better discussion with patients but also can guide treatment decisions
in the future once management is indicated clinically.
In summary, we agree with Yavorkovsky that treating
asymptomatic patients regardless of their molecular profile is
currently not recommended outside clinical trials, and we emphasized this notion throughout our review. However, we disagree that testing is not needed and suggest that knowing more
about the biological characteristics of a disease is only destined to help patients if used properly and judiciously. Finally, and similar to other malignant neoplasms, it is more likely
than not that treatment decisions for CLL in the years ahead
jamaoncology.com
will be based on molecular information that supplements clinical data to aid in decision making.
Chadi Nabhan, MD
Gordana Raca, MD, PhD
Y. Lynn Wang, MD, PhD
Author Affiliations: Section of Hematology and Oncology, Department of
Medicine, University of Chicago, Chicago, Illinois (Nabhan, Raca); Section of
Hematology/Oncology, Cancer Cytogenetics Laboratory, University of Chicago,
Chicago, Illinois (Raca); Division of Genomic and Molecular Pathology,
Department of Pathology, University of Chicago, Chicago, Illinois (Wang).
Corresponding Author: Chadi Nabhan, MD, Section of Hematology and
Oncology, Department of Medicine, University of Chicago Medicine, 5841 S
Maryland Ave, MC2115, Chicago, IL 60637 ([email protected]
.edu).
Conflict of Interest Disclosures: Dr Nabhan receives research funding from
Genentech. No other disclosures are reported.
1. Hallek M, Cheson BD, Catovsky D, et al; International Workshop on Chronic
Lymphocytic Leukemia. Guidelines for the diagnosis and treatment of chronic
lymphocytic leukemia: a report from the International Workshop on Chronic
Lymphocytic Leukemia updating the National Cancer Institute-Working Group
1996 guidelines. Blood. 2008;111(12):5446-5456.
2. Tam CS, Shanafelt TD, Wierda WG, et al. De novo deletion 17p13.1 chronic
lymphocytic leukemia shows significant clinical heterogeneity: the M. D.
Anderson and Mayo Clinic experience. Blood. 2009;114(5):957-964.
3. Awan FT, Byrd JC. New strategies in chronic lymphocytic leukemia: shifting
treatment paradigms. Clin Cancer Res. 2014;20(23):5869-5874.
CORRECTION
Incorrect Author Name Spelling: In the Special Communication titled “Improving Patient Safety in Clinical Oncology: Applying Lessons From Normal Accident
Theory” published in the May 14, 2015, online issue of JAMA Oncology (10.1001
/jamaoncol.2015.0891), an author’s name was misspelled. The correct spelling is
Ian Buchanan, MD, MPH. This article was corrected online.
Error in Figure: There was an error in the Figure in the Original Investigation by
Guérin et al,1 “Physician Underestimation of the Risk of Gastrointestinal Stromal
Tumor Recurrence After Resection,” published online in JAMA Oncology on July
23, 2015. The treatment durations at the bottom of the figure, <3 y and ⱖ3 y, should
have been set as ⱖ3 y and <3 y (the symbols were reversed). The article was corrected online.
1. Guérin A, Sasane M, Keir CH, et al. Physician underestimation of the risk of
gastrointestinal stromal tumor recurrence after resection [published online July
23, 2015]. JAMA Oncol. doi:10.1001/jamaoncol.2015.2407.
Error in Data Presentation in Figure: In the Research Letter “Efficacy of ProstateSpecific Antigen Screening: Use of Regression Discontinuity in the PLCO Cancer
Screening Trial,”1 published online August 20, 2015, there was an error in panel D
of the Figure. The scale of the y-axis should have been 1 through 5 instead of 10
through 50. This article was corrected online.
1. Shoag JE, Halpern J, Eisner B, et al. Efficacy of prostate-specific antigen
screening: use of regression discontinuity in the PLCO Cancer Screening Trial
[published online August 20, 2015]. JAMA Oncol. doi:10.1001/jamaoncol.2015
.2993.
(Reprinted) JAMA Oncology October 2015 Volume 1, Number 7
Copyright 2015 American Medical Association. All rights reserved.
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