- Email: [email protected]
In Reply to Bahl et al
Volume 88 Number 1 2014
Duodenal toxicity after fractionated chemoradiation for unresectable pancreatic cancer In Regard to Kelly et al To the Editor: We read with interest the study by Kelly et al (1) and compliment the authors for giving guidelines on an important dose constraint in pancreatic cancer management. However, we believe that their correlation of duodenal toxicity with radiation dose needs to be interpreted, keeping in mind the following: in their analysis, 70% of the patients underwent three-dimensional conformal radiation therapy. The radiation portals and beam energy used in these patients are not mentioned in the study. In the patients receiving intensity modulated radiation therapy, it is not clear whether pancreatic motion was taken into account. Additionally, it would have been interesting to know the SIB dose schedule used in their analysis, because all of the above can have bearing on treatmentrelated toxicity. Further, all patients in their study received concurrent chemotherapy, with the majority also getting both neoadjuvant and adjuvant chemotherapy. The duodenal toxicity profile can be different for protocols using only neoadjuvant chemotherapy or adjuvant chemotherapy compared with concurrent chemotherapy, and the duodenal dose constraint might be different with such regimens (2, 3). A prospective randomized analysis using image guided radiation therapy with adequate motion management and different chemotherapy schedules is called for to further answer this question. Amit Bahl, MD, DNB R. Kapoor, MD, DNB T. Bhattacharya, MD S.C. Sharma, MD Department of Radiation Oncology Post Graduate Institute of Medical Education and Research Chandigarh, India
Comments
237
technique using a mix of 6- and 18-MV photons as the patient’s anatomy dictated. For those patients who received intensity modulated radiation therapy, pancreatic motion was taken into account using an internal target volume when the tumor was within 1 cm of the duodenal mucosa, and the simultaneous integrated boost was commonly 63 Gy delivered in the standard 28 daily fractions. As such, we believe that the constraints defined in this study are generalizable for daily practice in which patients are treated with 25 to 28 fractions. In addition, this duodenal constraint will now be tested with prospective quality control on Radiation Therapy Oncology Group 0120, a randomized phase 2 trial evaluating local versus systemic treatment intensification with stratification for SMAD4 expression (3). We agree with Bahl et al that duodenal toxicity is likely to change with different chemotherapy regimens, and we advise caution when these regimens are examined, because prior studies have demonstrated that increased toxicity can compromise the benefits of treatment (4). Finally, we agree with the authors that there is there is an opportunity to further improve radiation therapy for pancreatic cancer. Advances in imaging, motion management, treatment planning, chemotherapy, and patient selection all have the potential to make radiation more effective and better tolerated. We only hope that our work helps as we move the field forward toward that goal. Patrick Kelly, MD MD Anderson Cancer Center Orlando Health Orlando, Florida Christopher H. Crane, MD Gastrointestinal Section Department of Radiation Oncology University of Texas MD Anderson Cancer Center Houston, Texas http://dx.doi.org/10.1016/j.ijrobp.2013.09.042
http://dx.doi.org/10.1016/j.ijrobp.2013.09.044
References
References
1. Bahl A, Kapoor R, Bhattacharya T. In regard to Kelly et al. Int J Radiat Oncol Biol Phys 2014;88:237. 2. Kelly P, Das P, Pinnix CC, et al. Duodenal toxicity after fractionated chemoradiation for unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys 2013;85:e143-e149. 3. RTOG Clinical Trials Study Group 0120. http://www.rtog.org/Clinical Trials/ProtocolTable/StudyDetails.aspx?studyZ120. Accessed October 24, 2013. 4. Chauffert B, Mornex F, Bonnetain F, et al. Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer: Definitive results of the 2000-01 FFCD/SFRO study. Ann Oncol 2008;19:1592-1599.
1. Kelly P, Das P, Pinnix CC, et al. Duodenal toxicity after fractionated chemoradiation for unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys 2013;85:e143-e149. 2. Murphy JD, Adusumilli S, Griffith KA, et al. Full-dose gemcitabine and concurrent radiotherapy for unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys 2007;68:801-808. 3. Talamonti MS, Catalano PJ, Vaughn DJ, et al. Eastern Cooperative Oncology Group Phase I trial of protracted venous infusion fluorouracil plus weekly gemcitabine with concurrent radiation therapy in patients with locally advanced pancreas cancer: A regimen with unexpected early toxicity. J Clin Oncol 2000;18:3384-3389.
In Reply to Bahl et al To the Editor: We thank Dr Bahl and colleagues for their interest and insightful comments (1). The goal of our study (2) was to provide constraints to guide standard practice and to provide a foundation for evaluating dose escalation regimens. In our study, as is the case in most centers around the world, the majority of the patients were treated with a four-field, three-dimensional conformal radiation
Prognostic utility of cell cycle progession score in men with prostate cancer after primary external beam radiation therapy In Regard to Freedland et al To the Editor: Oncologic molecular biomarkers are relevant for both prognostic (treatment-independent) and predictive
Duodenal toxicity after fractionated chemoradiation for unresectable pancreatic cancer In Regard to Kelly et al To the Editor: We read with interest the study by Kelly et al (1) and compliment the authors for giving guidelines on an important dose constraint in pancreatic cancer management. However, we believe that their correlation of duodenal toxicity with radiation dose needs to be interpreted, keeping in mind the following: in their analysis, 70% of the patients underwent three-dimensional conformal radiation therapy. The radiation portals and beam energy used in these patients are not mentioned in the study. In the patients receiving intensity modulated radiation therapy, it is not clear whether pancreatic motion was taken into account. Additionally, it would have been interesting to know the SIB dose schedule used in their analysis, because all of the above can have bearing on treatmentrelated toxicity. Further, all patients in their study received concurrent chemotherapy, with the majority also getting both neoadjuvant and adjuvant chemotherapy. The duodenal toxicity profile can be different for protocols using only neoadjuvant chemotherapy or adjuvant chemotherapy compared with concurrent chemotherapy, and the duodenal dose constraint might be different with such regimens (2, 3). A prospective randomized analysis using image guided radiation therapy with adequate motion management and different chemotherapy schedules is called for to further answer this question. Amit Bahl, MD, DNB R. Kapoor, MD, DNB T. Bhattacharya, MD S.C. Sharma, MD Department of Radiation Oncology Post Graduate Institute of Medical Education and Research Chandigarh, India
Comments
237
technique using a mix of 6- and 18-MV photons as the patient’s anatomy dictated. For those patients who received intensity modulated radiation therapy, pancreatic motion was taken into account using an internal target volume when the tumor was within 1 cm of the duodenal mucosa, and the simultaneous integrated boost was commonly 63 Gy delivered in the standard 28 daily fractions. As such, we believe that the constraints defined in this study are generalizable for daily practice in which patients are treated with 25 to 28 fractions. In addition, this duodenal constraint will now be tested with prospective quality control on Radiation Therapy Oncology Group 0120, a randomized phase 2 trial evaluating local versus systemic treatment intensification with stratification for SMAD4 expression (3). We agree with Bahl et al that duodenal toxicity is likely to change with different chemotherapy regimens, and we advise caution when these regimens are examined, because prior studies have demonstrated that increased toxicity can compromise the benefits of treatment (4). Finally, we agree with the authors that there is there is an opportunity to further improve radiation therapy for pancreatic cancer. Advances in imaging, motion management, treatment planning, chemotherapy, and patient selection all have the potential to make radiation more effective and better tolerated. We only hope that our work helps as we move the field forward toward that goal. Patrick Kelly, MD MD Anderson Cancer Center Orlando Health Orlando, Florida Christopher H. Crane, MD Gastrointestinal Section Department of Radiation Oncology University of Texas MD Anderson Cancer Center Houston, Texas http://dx.doi.org/10.1016/j.ijrobp.2013.09.042
http://dx.doi.org/10.1016/j.ijrobp.2013.09.044
References
References
1. Bahl A, Kapoor R, Bhattacharya T. In regard to Kelly et al. Int J Radiat Oncol Biol Phys 2014;88:237. 2. Kelly P, Das P, Pinnix CC, et al. Duodenal toxicity after fractionated chemoradiation for unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys 2013;85:e143-e149. 3. RTOG Clinical Trials Study Group 0120. http://www.rtog.org/Clinical Trials/ProtocolTable/StudyDetails.aspx?studyZ120. Accessed October 24, 2013. 4. Chauffert B, Mornex F, Bonnetain F, et al. Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer: Definitive results of the 2000-01 FFCD/SFRO study. Ann Oncol 2008;19:1592-1599.
1. Kelly P, Das P, Pinnix CC, et al. Duodenal toxicity after fractionated chemoradiation for unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys 2013;85:e143-e149. 2. Murphy JD, Adusumilli S, Griffith KA, et al. Full-dose gemcitabine and concurrent radiotherapy for unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys 2007;68:801-808. 3. Talamonti MS, Catalano PJ, Vaughn DJ, et al. Eastern Cooperative Oncology Group Phase I trial of protracted venous infusion fluorouracil plus weekly gemcitabine with concurrent radiation therapy in patients with locally advanced pancreas cancer: A regimen with unexpected early toxicity. J Clin Oncol 2000;18:3384-3389.
In Reply to Bahl et al To the Editor: We thank Dr Bahl and colleagues for their interest and insightful comments (1). The goal of our study (2) was to provide constraints to guide standard practice and to provide a foundation for evaluating dose escalation regimens. In our study, as is the case in most centers around the world, the majority of the patients were treated with a four-field, three-dimensional conformal radiation
Prognostic utility of cell cycle progession score in men with prostate cancer after primary external beam radiation therapy In Regard to Freedland et al To the Editor: Oncologic molecular biomarkers are relevant for both prognostic (treatment-independent) and predictive