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Journal of Thoracic Oncology:
doi: 10.1097/JTO.0b013e318245a042
Letter to the Editor

Induction Chemotherapy Inevitably Leads to Inferior Outcome in Combined Modality Treatment for Unresectable Stage III Non-small Cell Lung Cancer

Jeremic, Branislav MD, PhD; Videtic, Gregory M.M. MD

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Institute of Lung Diseases, Sremska Kamenica, Serbia

The Cleveland Clinic, Cleveland, Ohio

Disclosure: The authors declare no conflicts of interest.

Address for correspondence: Branislav Jeremic, MD, PhD, Institute of Lung Diseases, Institutski put 4, 21204 Sremska kamenica, Serbia. E-mail: nebareje@gmail.com

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To the Editor:

We read with interest the recent retrospective report of Chen et al.1 on the deleterious effects of delayed initiation of radiotherapy (RT) after induction chemotherapy (CHT) in stage III non-small cell lung cancer (NSCLC) due to tumor regrowth occurring within a few weeks. They have concluded that RT treatment planning should begin as soon as possible after the administration of induction CHT to maximize its benefits and provided a volumetric analysis of tumors to support their conclusion of accelerated repopulation as the mechanism for regrowth during delays. Their results in fact reconfirm the study of El-Sharouni et al.2 which compared computed tomography (CT) scans-based assessment of tumor changes before and after induction CHT, with an emphasis on the time interval from the last induction CHT cycle to the timing of the RT treatment planning CT scan. They showed that during the waiting period (for the planning CT scan and start of RT), a total of 41% of all tumors became incurable. Bozcuk et al.3 recently looked at the benefits of induction CHT before RT in NSCLC using a meta-analytical approach with meta-regression analysis. Using 13 completed randomized clinical trials involving a total of 2776 patients, they found that the time to RT initiation was inversely associated with the benefit from induction CHT at 2 (p = 0.050) and 3 years (p = 0.093).

As noted by the authors, a range of prospective randomized clinical trials followed by recent meta-analyses4 have confirmed that in unresectable stage III NSCLC patients meeting the selection criteria for such trials, the standard of care is concurrent RT-CHT, with CHT initiated on day 1 of RT, as compared with sequential CHT followed by RT. Furthermore, the recently published randomized trial (CALGB 39801)5 of concurrent RT-CHT with or without the addition of induction CHT showed that the experimental arm generated excess toxicity and provided no survival benefit over concurrent RT-CHT alone.5 With this evidence in mind, the present report by Chen et al. fails to adequately justify their conclusion about future clinical research in this setting without clear upfront patient and/or tumor selection criteria which may prompt an indication for the use of induction CHT. In addition, they identify “logistical/scheduling constraints in 14 of 21 cases” which are otherwise not characterized as the basis for delays in RT initiation after induction. This suggests a number of variables in their study population which would not conventionally make these patients trial eligible. Without better characterization of their population, it then becomes difficult to understand why one should optimize what is already an inferior (i.e., induction CHT) approach to managing stage III NSCLC but not further optimize the better (RT-CHT) approach associated with the optimal survival.

We share the authors’ goals in providing the best care possible for patients confronting locally advanced lung cancer and agree that optimizing the delivery of RT is a priority. The old notion of “doing something while the patient waits for the radiotherapy planning scan” is clearly not tenable. A more detailed analysis of the clinical circumstances in the present series would have further served to justify that proposition.

Branislav Jeremic, MD, PhD

Institute of Lung Diseases

Sremska Kamenica, Serbia

Gregory M.M. Videtic, MD

The Cleveland Clinic

Cleveland, Ohio

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REFERENCES

1. Chen CP, Weinberg VK, Jahan TM, et al. Implications of delayed initiation of radiotherapy accelerated repopulation after induction chemotherapy for stage III non-small cell lung cancer. J Thorac Oncol. 2011;6:1857–1864

2. El Sharouni SY, Kal HB, Battermann JJ.. Accelerated regrowth of non-small-cell lung tumors after induction chemotherapy. Br J Cancer. 2003;89:2184–2189

3. Bozcuk H, Artac M, Ozdogan M.. Correlates of benefit from neoadjuvant chemotherapy before radiotherapy in non-small cell lung cancer: a meta-analytical approach with meta-regression analysis. J BUON. 2010;15:43–50

4. Aupérin A, Le Péchoux C, Rolland E, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010;28:2181–2190

5. Vokes EE, Herndon JE II, Kelley MJ, et al. Cancer and Leukemia Group B. Induction chemotherapy followed by chemoradiotherapy compared with chemoradiotherapy alone for regionally advanced unresectable stage III Non-small-cell lung cancer: Cancer and Leukemia Group B. J Clin Oncol. 2007;25:1698–1704

© 2012International Association for the Study of Lung Cancer

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