Comments International Journal of Radiation Oncology � Biology � Physics932

I would like to underline the fact that 8 of 10 patients arestill alive and well. Of the 2 deceased patients mentionedby the commentators, 1 patient died because of a suddenblockage of the stent inserted a few weeks earlier, and theother patient died of cardiac failure 40 years after thecombined modality treatment.

I do not believe that a Framingham score could bemultiplied by a factor derived from radiation planning, asthere are large radiation dose gradients along the coronaryartery network partly because of the variety of shapes,sizes, and geographical locations of Hodgkin lymphomamediastinal masses (A. Moignier, work in preparation).

I do not believe that a score-based approach would helpdetect patients with coronary artery abnormalities withcertainty. It will remain, at best, a more or less strongassumption of possible disease, unless a CCTA is per-formed. Such patients might be deprived of more aggres-sive medical and/or surgical procedures that could prolongtheir lives as well as their quality of life. On the other hand,a score-based approach (possibly including telomere lengthmeasurements, a genetic approach suggested in the article)could help determine which patients really require a CCTAor any other radiological investigations.

As for the controversy about the value of revasculari-zation (3), it was not the scope of the article.

Theodore Girinsky, MDDepartment of Radiation Oncology

Institut Gustave RoussyVillejuif, France

http://dx.doi.org/10.1016/j.ijrobp.2014.04.001

References

1. Myrehaug S, Pintilie M, Tsang R, et al. Cardiac morbidity following

modern treatment for Hodgkin lymphoma: Supra-additive cardiotox-

icity of doxorubicin and radiation therapy. Leuk Lymphoma 2008;49:

1486-1493.

2. Girinsky T, M’Kacher R, Lessard N, et al. Prospective coronary heart

disease screening in asymptomatic Hodgkin lymphoma patients using

coronary computed tomography angiography: Results and risk factor

analysis. Int J Radiat Oncol Biol Phys 2014;89:59-66.

3. Gyenes GT. In regard to Girinsky et al. Int J Radiat Oncol Biol Phys

2014;89:931.

Watch and Wait FollowingNeoadjuvant Chemoradiationin Rectal Cancer

In Regard to Habr-Gama et al

To the Editor:We read with great interest the study by Habr-Gama et al (1) and congratulate the authors for reporting onan alternative nonsurgical strategy for patients with rectalcancer that achieved a clinical complete response to

preoperative chemoradiation. Because the current standardtreatment for locally advanced rectal cancer patients (pre-operative chemoradiation and total mesorectal excision) isassociated with significant postoperative and functional(anorectal and genitourinary) morbidity, surveillancewithout any immediate surgery and postchemoradiationreduced local surgery (eg, transanal microsurgery) areinteresting alternatives to be prospectively explored andtested against in carefully selected candidates (2). Nonethe-less, successful implementation of the wait-and-see treat-ment strategy requires accurately distinguishing betweenpatients who are more likely to achieve a complete patho-logic response and those who still harbor residual cancer (3).To date, only magnetic resonance imaging posttreatmentassessment has been prospectively correlated with tumorresponse and long-term outcomes (4). The long time frame ofthe study period (20 years) inevitably included the incorpo-ration of new diagnostic tools for baseline staging and reas-sessment only in a small group of patients, limiting thepotential widespread application of this strategy in currentclinical practice. On the other hand, a large proportion of thestudied patients had early stage disease in which the risk ofrelapse might have been too small towarrant the benefit fromradiation therapy and could potentially have been treatedwith initial surgery alone (5).

In order to safely move toward the anal canal cancerorgan-preserving equivalent approach (6), tailored surgicaltreatment should be restricted to highly selected rectalcancer patients. We believe that further research, develop-ment, and standardization of postneoadjuvant treatmentevaluation methods is of paramount importance for theadequate design of future studies that could adapt patienttreatment and personalize strategies before definitive sur-gical treatment. The ultimate decision will depend on thegoal of the treatment, taking into account the patient’spreference, survival outcomes, toxicity, and detailed qualityof life results in order to understand the full picture of thenonsurgical management opportunities (7).

Claudio V. Sole, MD, PhDService of Radiation Oncology

Instituto de RadiomedicinaSantiago, Chile

Felipe A. Calvo, MD, PhDDepartment of Oncology

Hospital General Universitario Gregorio MaranonMadrid, Spain

http://dx.doi.org/10.1016/j.ijrobp.2014.04.006

References

1. Habr-GamaA,Gama-Rodrigues J, Sao JuliaoGP, et al. Local recurrence

after complete clinical response andwatch andwait in rectal cancer after

neoadjuvant chemoradiation: Impact of salvage therapy on local disease

control. Int J Radiat Oncol Biol Phys 2014;88:822-828.

Volume 89 � Number 4 � 2014 Comments 933

2. Bujko K, Richter P, Smith FM, et al. Preoperative radiotherapy and

local excision of rectal cancer with immediate radical re-operation for

poor responders: A prospective multicentre study. Radiother Oncol

2013;106:198-205.

3. Maas M, Nelemans PJ, Valentini V, et al. Long-term outcome in pa-

tients with a pathological complete response after chemoradiation for

rectal cancer: A pooled analysis of individual patient data. Lancet

Oncol 2010;11:835-844.

4. Patel UB, Taylor F, Blomqvist L, et al. Magnetic resonance imaging-

detected tumor response for locally advanced rectal cancer predicts

survival outcomes: MERCURY experience. J Clin Oncol 2011;29:

3753-3760.

5. van Gijn W, Marijnen CA, Nagtegaal ID, et al. Preoperative radio-

therapy combined with total mesorectal excision for resectable rectal

cancer: 12-year follow-up of the multicentre randomised controlled

TME trial. Lancet Oncol 2011;12:575-582.

6. James RD, Glynne-Jones R, Meadows HM, et al. Mitomycin or

cisplatin chemoradiation with or without maintenance chemotherapy

for treatment of squamous-cell carcinoma of the anus (ACT II): A

randomised, phase 3, open-label, 2 � 2 factorial trial. Lancet Oncol

2013;14:516-524.

7. Pieterse AH, Stiggelbout AM, Baas-Thijssen MC, et al. Benefit from

preoperative radiotherapy in rectal cancer treatment: Disease-free pa-

tients’ and oncologists’ preferences. Br J Cancer 2007;97:717-724.

In Reply to Sole and Calvo

To the Editor: We thank the authors for their thoughtfulcomments on the limitations of our study (1, 2). We agreethat the long time period in which patients were managed bywatch-and-wait after complete clinical response (cCR) mayhave included different assessment technologies over time,such as magnetic resonance imaging (MRI), positron emis-sion tomography/computed tomography (PET/CT), andeven transanal endoscopicmicrosurgery (TEMs) for selectedpatients. In a proportion of these patients, clinical assessmentalone with digital rectal examination (the “bioprobe”)playing the central role was the sole tool in determination ofresponse (3). Ultimately, it may be difficult to translate thesefindings into current clinical practice of rectal cancer.However, one could argue that without the use of these stillevolving but already available technologies, it was evenmore difficult to assess tumor response in the early yearsof this experience. Without any information for high-resolution MR with precise tumor regression grade(mrTRG) classification, patterns of low-signal intensity,PET/CT fluorodeoxyglucose uptake, and excisional biopsiesusing TEM, assessment of tumor response would almostinevitably be far from perfect (4-6). Even in this adversesetting, our results were acceptable in terms of local diseasecontrol considering watch-and-wait and salvage proceduresin the event of local recurrence or tumor regrowth (1). Webelieve this is an important message of our data.

We also agree that a significant proportion of casesprobably harbored early stage disease, in which the risk oflocal recurrence rates might have been too small to warrantthe benefit of radiation therapy followed by radical surgery.However, avoiding radical surgery in patients with cCR

may ultimately be a significant benefit in itself. It is stillundetermined whether the detrimental effects of CRT(alone) are actually worse than the detrimental effects ofradical surgery alone, particularly when there is no survivaladvantage (7, 8). Ultimately, these same patients with earlystage disease are probably those more likely to developcomplete clinical response (cCR), avoid radical surgery,and benefit the most from CRT (9, 10). Therefore, if watch-and-wait is not to be considered, perhaps neoadjuvant CRTshould be restricted to the very worst high-risk tumors(those that are unlikely to develop cCR) (11).

Finally, further improvements in imaging modalities thathave already been prospectively studied for the assessmentof response (including PET/CT and MRI) are warranted.In addition, there is hope that molecular biology will playa central role in predicting and monitoring response, alto-gether this approach will enable us to offer truly person-alized selection of patients before and after CRT foralternative treatment strategies.

Angelita Habr-Gama, MD, PhDJoaquim Gama-Rodrigues, MD, PhDAngelita and Joaquim Gama Institute

Sao Paulo, BrazilUniversity of Sao Paulo School of Medicine

Sao Paulo, Brazil

Rodrigo O. Perez, MD, PhDAngelita and Joaquim Gama Institute

Sao Paulo, BrazilColorectal Surgery Division

University of Sao Paulo School of MedicineSao Paulo, Brazil

Ludwig Institute for Cancer ResearchSao Paulo BranchSao Paulo, Brazil

http://dx.doi.org/10.1016/j.ijrobp.2014.04.005

References

1. Habr-Gama A, Gama-Rodrigues J, Sao Juliao GP, et al. Local recur-

rence after complete clinical response and watch and wait in rectal

cancer after neoadjuvant chemoradiation: Impact of salvage therapy on

local disease control. Int J Radiat Oncol Biol Phys 2014;88:822-828.

2. Sole C, Calvo F. Int J Radiat Oncol Biol Phys 2014;89:932-933.

3. Habr-Gama A, Perez RO, Wynn G, et al. Complete clinical response

after neoadjuvant chemoradiation therapy for distal rectal cancer:

Characterization of clinical and endoscopic findings for standardiza-

tion. Dis Colon Rectum 2010;53:1692-1698.

4. Patel UB, Taylor F, Blomqvist L, et al. Magnetic resonance imaging-

detected tumor response for locally advanced rectal cancer predicts

survival outcomes: MERCURY experience. J Clin Oncol 2011;29:

3753-3760.

5. Lambregts DM, Maas M, Bakers FC, et al. Long-term follow-up

features on rectal MRI during a wait-and-see approach after a clin-

ical complete response in patients with rectal cancer treated with

chemoradiotherapy. Dis Colon Rectum 2011;54:1521-1528.