- Email: [email protected]
A phase II trial of induction chemotherapy followed by continuous hyperfractionated accelerated radiotherapy in locally advanced non-small cell lung cancer
258
Letters to the Editor / Radiotherapy and Oncology 95 (2010) 257–259
Received 21 December 2009 Revised 17 February 2010 Accepted 17 February 2010 0167-8140/$ - see front matter Ó 2010 Published by Elsevier Ireland Ltd. doi:10.1016/j.radonc.2010.02.015
2-year, it seems far from be comparable to concomitant chemoradiation, unless longer follow-up would confirm the outcome. In our limited experience, the 5-year survival for definitive treatments reached 21%, presuming that this strategy maintains validity, at least in selected patients. References
A phase II trial of induction chemotherapy followed by continuous hyperfractionated accelerated radiotherapy in locally advanced non-small cell lung cancer
To the Editor, We read with great interest the paper by Jenkins et al. on induction chemotherapy followed by CHART in locally advanced NSCLC [1], since a similar approach has been carried out in our Institution too [2]. Being our experience hampered by low accrual and treatment heterogeneity (patients was irradiated with either post-operative or definitive purpose), it’s not our aim to compare our results to the ones reported in the present report. Nevertheless, a similitude does exists and some statements seem worthwhile to be discussed. Authors report a protocol adherence of 100%, with all of enrolled patients concluding planned radiotherapy. If confirmed, the absence of metastatic spread during the whole course of chemotherapy is very interesting, especially considering the high rate of stage IIIB patients and the absence of PET scan as staging procedure. Although Jenkins’ primary outcome was toxicity, low emphasis is given to radiation-induced complications, maybe due to the low rate observed. Authors report a grade >2 oesophagitis in a single patient, whereas pneumonitis rate is 10%, but no comments support these findings, except for a presumed favourable impact of the interval between chemotherapy and radiotherapy. As some data seem to attribute a predictive role to pre-treatment disphagia in the genesis of radiation-induced oesophagitis [3], it should be interesting to known whether this factor is known, thus explaining reported results, which are indeed lower than the ‘‘original” CHART findings (‘‘severe” toxicity rate of 19%, with radiotherapy alone) [4]. Although contradictory [5,6], dosimetric parameters would also be interesting to be commented, if known. We failed to discover any correlation between oesophagitis and dose–volume histograms, but results may be likely under-powered by the low number of patients and events [7]. We agree when authors state that ‘‘response to chemotherapy should not be used to select patients as being suitable for subsequent radiotherapy”; nevertheless, we believe that the main advantage of induction chemotherapy is to exclude progressive patients after a systemic treatment, for an aggressive local treatment (with the same approach followed by surgeons for chemotherapy before resection). High local control and low incidence of ‘‘in-field” recurrence (18%) are emphasized by authors. Apart from a unclear specification of CTV contouring and ‘‘in-field” definition, we believe that it would have been more correct to focus discussion on locoregional recurrences too, especially considering that radiotherapy has been carried out without elective irradiation, and the only diagnostic procedure for nodal assessment has been computed tomography. Nevertheless, obtained results are fascinating and, looking at those reported in our experience (loco-regional recurrence rate of 33%, for definitive irradiation), clearly better, despite the lower biological effective dose of CHART (BED10 of 62 Gy10), compared to our schedule (BED10 of 72 Gy10). The reported survival (median: 15.7 months) warrants further investigations of this strategy; nevertheless, looking at results after
[1] Jenkins P, Anderson S, Wronski S, et al. A phase II trial of induction chemotherapy followed by continuous hyperfractionated accelerated radiotherapy in locally advanced non-small cell lung cancer. Radiother Oncol 2009;93:396–401. [2] Catalano G, De Pas T, Spaggiari L, et al. ‘‘Three-times daily radiotherapy after chemotherapy in stage III non-small cell lung cancer. Single-institution prospective study”. Anticancer Res 2008;28:4121–7. [3] Maguire PD, Sibley GS, Zhou SM, et al. Clinical and dosimetric predictors of radiation-induced esophageal toxicity. Int J Radiat Oncol Biol Phys 1999;45:97–103. [4] Saunders M, Dische S, Barrett A, et al. Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small-cell lung cancer: a randomised multicentre trial. CHART Steering Committee. Lancet 1997;350:161–5. [5] Choi H, La Porte K, Knill-Selby E, et al. Esophagitis in combined modality therapy for locally advanced non-small cell lung cancer. Semin Radiat Oncol 1999;9:90–6. [6] Werner-Wasik M, Pequignot E, Leeper D, et al. Predictors of severe esophagitis include use of concurrent chemotherapy, but not the length of irradiated esophagus: a multivariate analysis of patients with lung cancer treated with nonoperative therapy. Int J Radiat Oncol Biol Phys 2000;48:689–96. [7] Catalano G, Jereczek-Fossa BA, De Pas T, et al. Three-time daily radiotherapy with induction chemotherapy in locally advanced non-small cell lung cancer: feasibility and toxicity study. Strahlenther Onkol 2005;181:363–71.
Gianpiero Catalano a,* Gaia Piperno b Roberto Orecchia b,c a Unit of Radiotherapy, Multimedica Holding Clinical Institute, Castellanza, Italy b Division of Radiotherapy, European Institute of Oncology, Milan, Italy c Chair of Radiotherapy, University of Milan, Italy * Corresponding author. Present address: Division of Radiotherapy, Multimedica Holding S.p.a., Castellanza (VA), Italy. E-mail addresses: [email protected] (G. Catalano) Received 22 January 2009 Revised 2 March 2010 Accepted 7 March 2010
0167-8140/$ - see front matter Ó 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.radonc.2010.03.011
In response to Dr. Catalano et al. To the Editor: I thank Dr. Catalano and colleagues for their interest in our paper [1]. We agree with them that the results of studies combining induction chemotherapy with accelerated radiotherapy look promising, underlying the importance of overall treatment time for local tumour control. In answer to the specific points they raise concerning our trial. All 40 patients completed the planned treatment. Whilst we did not formally restage patients after chemotherapy, CT planning scans of the thorax were performed before and after chemotherapy. We have previously reported that tumour volume reduced by a mean of 37% with chemotherapy [2]. Only 1 patient developed progressive disease (a small pleural effusion) and nonetheless still went onto receive radiotherapy. The low rate of radiation toxicity that we observed was reassuring and compares favourably with both the results of synchronous
Letters to the Editor / Radiotherapy and Oncology 95 (2010) 257–259
Received 21 December 2009 Revised 17 February 2010 Accepted 17 February 2010 0167-8140/$ - see front matter Ó 2010 Published by Elsevier Ireland Ltd. doi:10.1016/j.radonc.2010.02.015
2-year, it seems far from be comparable to concomitant chemoradiation, unless longer follow-up would confirm the outcome. In our limited experience, the 5-year survival for definitive treatments reached 21%, presuming that this strategy maintains validity, at least in selected patients. References
A phase II trial of induction chemotherapy followed by continuous hyperfractionated accelerated radiotherapy in locally advanced non-small cell lung cancer
To the Editor, We read with great interest the paper by Jenkins et al. on induction chemotherapy followed by CHART in locally advanced NSCLC [1], since a similar approach has been carried out in our Institution too [2]. Being our experience hampered by low accrual and treatment heterogeneity (patients was irradiated with either post-operative or definitive purpose), it’s not our aim to compare our results to the ones reported in the present report. Nevertheless, a similitude does exists and some statements seem worthwhile to be discussed. Authors report a protocol adherence of 100%, with all of enrolled patients concluding planned radiotherapy. If confirmed, the absence of metastatic spread during the whole course of chemotherapy is very interesting, especially considering the high rate of stage IIIB patients and the absence of PET scan as staging procedure. Although Jenkins’ primary outcome was toxicity, low emphasis is given to radiation-induced complications, maybe due to the low rate observed. Authors report a grade >2 oesophagitis in a single patient, whereas pneumonitis rate is 10%, but no comments support these findings, except for a presumed favourable impact of the interval between chemotherapy and radiotherapy. As some data seem to attribute a predictive role to pre-treatment disphagia in the genesis of radiation-induced oesophagitis [3], it should be interesting to known whether this factor is known, thus explaining reported results, which are indeed lower than the ‘‘original” CHART findings (‘‘severe” toxicity rate of 19%, with radiotherapy alone) [4]. Although contradictory [5,6], dosimetric parameters would also be interesting to be commented, if known. We failed to discover any correlation between oesophagitis and dose–volume histograms, but results may be likely under-powered by the low number of patients and events [7]. We agree when authors state that ‘‘response to chemotherapy should not be used to select patients as being suitable for subsequent radiotherapy”; nevertheless, we believe that the main advantage of induction chemotherapy is to exclude progressive patients after a systemic treatment, for an aggressive local treatment (with the same approach followed by surgeons for chemotherapy before resection). High local control and low incidence of ‘‘in-field” recurrence (18%) are emphasized by authors. Apart from a unclear specification of CTV contouring and ‘‘in-field” definition, we believe that it would have been more correct to focus discussion on locoregional recurrences too, especially considering that radiotherapy has been carried out without elective irradiation, and the only diagnostic procedure for nodal assessment has been computed tomography. Nevertheless, obtained results are fascinating and, looking at those reported in our experience (loco-regional recurrence rate of 33%, for definitive irradiation), clearly better, despite the lower biological effective dose of CHART (BED10 of 62 Gy10), compared to our schedule (BED10 of 72 Gy10). The reported survival (median: 15.7 months) warrants further investigations of this strategy; nevertheless, looking at results after
[1] Jenkins P, Anderson S, Wronski S, et al. A phase II trial of induction chemotherapy followed by continuous hyperfractionated accelerated radiotherapy in locally advanced non-small cell lung cancer. Radiother Oncol 2009;93:396–401. [2] Catalano G, De Pas T, Spaggiari L, et al. ‘‘Three-times daily radiotherapy after chemotherapy in stage III non-small cell lung cancer. Single-institution prospective study”. Anticancer Res 2008;28:4121–7. [3] Maguire PD, Sibley GS, Zhou SM, et al. Clinical and dosimetric predictors of radiation-induced esophageal toxicity. Int J Radiat Oncol Biol Phys 1999;45:97–103. [4] Saunders M, Dische S, Barrett A, et al. Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small-cell lung cancer: a randomised multicentre trial. CHART Steering Committee. Lancet 1997;350:161–5. [5] Choi H, La Porte K, Knill-Selby E, et al. Esophagitis in combined modality therapy for locally advanced non-small cell lung cancer. Semin Radiat Oncol 1999;9:90–6. [6] Werner-Wasik M, Pequignot E, Leeper D, et al. Predictors of severe esophagitis include use of concurrent chemotherapy, but not the length of irradiated esophagus: a multivariate analysis of patients with lung cancer treated with nonoperative therapy. Int J Radiat Oncol Biol Phys 2000;48:689–96. [7] Catalano G, Jereczek-Fossa BA, De Pas T, et al. Three-time daily radiotherapy with induction chemotherapy in locally advanced non-small cell lung cancer: feasibility and toxicity study. Strahlenther Onkol 2005;181:363–71.
Gianpiero Catalano a,* Gaia Piperno b Roberto Orecchia b,c a Unit of Radiotherapy, Multimedica Holding Clinical Institute, Castellanza, Italy b Division of Radiotherapy, European Institute of Oncology, Milan, Italy c Chair of Radiotherapy, University of Milan, Italy * Corresponding author. Present address: Division of Radiotherapy, Multimedica Holding S.p.a., Castellanza (VA), Italy. E-mail addresses: [email protected] (G. Catalano) Received 22 January 2009 Revised 2 March 2010 Accepted 7 March 2010
0167-8140/$ - see front matter Ó 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.radonc.2010.03.011
In response to Dr. Catalano et al. To the Editor: I thank Dr. Catalano and colleagues for their interest in our paper [1]. We agree with them that the results of studies combining induction chemotherapy with accelerated radiotherapy look promising, underlying the importance of overall treatment time for local tumour control. In answer to the specific points they raise concerning our trial. All 40 patients completed the planned treatment. Whilst we did not formally restage patients after chemotherapy, CT planning scans of the thorax were performed before and after chemotherapy. We have previously reported that tumour volume reduced by a mean of 37% with chemotherapy [2]. Only 1 patient developed progressive disease (a small pleural effusion) and nonetheless still went onto receive radiotherapy. The low rate of radiation toxicity that we observed was reassuring and compares favourably with both the results of synchronous