- Email: [email protected]
In Response to Dr. Russi and Colleagues
Int. J. Radiation Oncology Biol. Phys., Vol. 79, No. 4, pp. 1278–1281, 2011 Copyright Ó 2011 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/$ - see front matter
LETTERS TO THE EDITOR 2. Potthoff K, Hofheinz R, Hassel JC, et al. Interdisciplinary management of EGFR-inhibitor-induced skin reactions: a German expert opinion. Ann Oncol 2010. Available at: http://www.ncbi.nlm.nih.gov.bvs.cilea.it/ pubmed/20709812 [accessed September 2, 2010]. 3. Merlano M, Russi E, Benasso M, et al. Cisplatin-based chemoradiation plus cetuximab in locally advanced head and neck cancer: A phase II clinical study. Ann Oncol 2010. Available at: http://annonc.oxfordjournals. org/content/early/2010/09/01/annonc.mdq412.abstract.html?ijkey=eud MvoKseHjz1pz&keytype=ref [accessed September 2, 2010]. 4. Su X, Lacouture ME, Jia Y, et al. Risk of high-grade skin rash in cancer patients treated with cetuximab—an antibody against epidermal growth factor receptor: Systemic review and meta-analysis. Oncology 2009;77:124–133. 5. US Department of Health and Human Services, National Institutes of Health National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) and Common Toxicity Criteria (CTC) v. 4. 2009. Available at: http://evs.nci.nih.gov/ftp1/CTCAE/About.html [accessed July 10, 2010]. 6. Lacouture ME, Maitland ML, Segaert S, et al. A proposed EGFR inhibitor dermatologic adverse event-specific grading scale from the MASCC skin toxicity study group. Support Care Cancer 2010;18:509–522. 7. Pastore S, Mascia F, Mariani V, et al. The epidermal growth factor receptor system in skin repair and inflammation. J Invest Dermatol 2008;128 (6):1365–1374. 8. Budach W, Bolke E, Homey B. Severe cutaneous reaction during radiation therapy with concurrent cetuximab. N Engl J Med 2007;357:514–515. 9. B€olke E, Gerber PA, Lammering G, et al. Development and management of severe cutaneous side effects in head-and-neck cancer patients during concurrent radiotherapy and cetuximab. Strahlenther Onkol 2008;184: 105–110.
CETUXIMAB-RELATED RADIATION DERMATITIS IN HEAD-AND-NECK CANCER PATIENTS: IN REGARD TO STUDER ET AL. (INT J RADIAT ONCOL BIOL PHYS IN PRESS) To the Editor: We read with interest the paper by Studer et al. (1). The authors raise an important point: the absence of a specific and useful grading system to assess cetuximab-related radiation dermatitis (CrRD). In fact, there is too much subjectivity in using two scales of grading—as the authors did—to define the severity of this toxicity. So, although their conclusions may be correct, their objectivation is weak. The authors used two of three scales described in NCI Common Toxicity Criteria for Adverse Events grading system v. 3 (CTCAEv3), usually adopted in literature (2, 3) to describe cetuximab skin toxicity: 1) skin rash (SR), 2) acneiform rash (AR), and 3) radiation dermatitis (RD). These scales are often used singly or ‘‘in mixed form.’’ This fact can explain the variability of nomenclature and of incidence of Grade 3-4 toxicity reported by the literature (1). Studer states in the Discussion section: ‘‘This may in part result from nonspecific dermatitis grading systems (CTCAE, RTOG/EORTC), used to assess cetuximabrelated dermal changes’’ and Su (4), in a review of cetuximab toxicity, stressed ‘‘.the imperfection of NCI-CTC grading criteria, which may fail to reflect the clinical situation.’’ Indeed, the more recent CTCAE v.4 (5) and MASCC (Multinational Association for Supportive Care in Cancer) skin toxicity proposal (6) introduce some improvements, but the issue of the ‘‘in-field toxicity,’’ in our opinion, did not receive enough attention. Although RD is adequate to describe radiation toxicity, it is not suitable to describe the complex clinical aspect of CrRD. Actually, the two treatments may interfere each other with supra-additive effect because of the interference of cetuximab on reparative reaction induced by radiation, and additive effect, because of the sum of the two distinct toxicities: RD (i.e., erythema, dry and moist desquamation, and necrosis) and cetuximab toxicity (i.e., xerosis, inflammatory reaction (7), and folliculitis). This gives a different meaning to the classical RD signs: the thin, painless scurf of the dry desquamation, in the context of xerotic and inflamed dermis of CrRD, becomes thick, hurting, and painful scales. Moreover, the full thickness necrosis (well described by Budach et al. (8)) rapidly heals without disfiguring scar (9): can this have the same clinical meaning of RD necrosis? Perhaps we need to give more importance to in-field CrCD than it has been given so far (2, 6), by defining a specific scoring system, that leaves behind RD and defines a new scale, that takes into account what we have learned in the last years.
IN RESPONSE TO DR. RUSSI AND COLLEAGUES To the Editor: We thank Dr. Russi and colleagues for their interest in our publication. We agree that clear and objective nomenclature for grading cetuximab-related radiation dermatitis (CrRD) is lacking, and this point was clearly made in our discussion. However, we wish to clarify the manner in which we graded radiation dermatitis in our patient cohort. The assertion that we used two of the three scales described in the NCI Common Toxicity Criteria for Adverse Events v. 3 (CTCAEv3) to evaluate radiation dermatitis is incorrect, or perhaps a misinterpretation of our methodology. We used the ‘‘rash: dermatitis associated with radiation’’ scale alone and not either of the ‘‘rash: acne/ acneiform’’ or ‘‘rash/desquamation’’ scales (Table 1). In addition, we grouped Grade 3 and Grade 4 dermatitis together for the purpose of our analysis because we consider both toxicity grades to be clinically significant. The radiation dermatitis scale was used in a consistent manner to assess radiation toxicity in our patient population, for both the cetuximab and cisplatin groups. As a result, we feel that our results are as robust and objective as other published series. We acknowledge in our discussion that comparison of data from other centers is limited when different toxicity scales or definitions of CrRD are used. In addition, our use of bolus may be more frequent, and our results demonstrating an association between increased incidence of dermatitis and use of bolus may partly explain the higher incidence of CrRD in our patient population. Until a more uniform and universally accepted nomenclature is in use, we recommend that institutions use one grading scale in a consistent manner and that patients with extensive areas of bolus material be carefully monitored for acute skin toxicity.
ELVIO G. RUSSI, M.D. Department of Radiation Oncology Santa Croce General Hospital Cuneo, Italy GIANMAURO NUMICO, M.D. Department of Medical Oncology University of Parini Hospital Aosta, Italy MARCO C. MERLANO, M.D. Department of Medical Oncology Santa Croce General Hospital Cuneo, Italy CARMINE PINTO, M.D. Medical Oncology Unit S. Orsola-Malpighi Hospital Bologna, Italy doi:10.1016/j.ijrobp.2010.10.047
GABRIELA STUDER, M.D. MICHELLE BROWN, M.D. CHRISTOPH GLANZMANN, M.D. Department of Radiation Oncology University Hospital Zurich Zurich, Switzerland
1. Studer G, Brown M, Salgueiro EB, et al. Grade 3/4 dermatitis in head and neck cancer patients treated with concurrent cetuximab and IMRT. Int J Radiat Oncol Biol Phys 2010. Available at: http://www.redjournal.org/ search/quick [accessed August 28, 2010].
doi:10.1016/j.ijrobp.2010.10.045 1278
Letters to the Editor
1279
Table 1. NCI common toxicity criteria for adverse events v. 3 (CTCAEv3)
Rash/desquamation
Rash
Macular or papular eruption or erythema without associated symptoms
Macular or papular eruption or erythema with pruritus or other associated symptoms; localized desquamation or other lesions covering \50% of body surface area
Rash: acne/ acneiform
Acne
Intervention not indicated
Intervention indicated
Rash: dermatitis associated with radiation Select: Chemoradiation Radiation
Dermatitis Select
Faint erythema or dry desquamation
Moderate to brisk erythema; patchy moist desquamation, mostly confined to skin folds and creases; moderate edema
Severe, generalized erythroderma or macular, papular, or vesicular eruption; desquamation covering $50% body surface area Associated with pain, disfigurement, ulceration, or desquamation Moist desquamation other than skin folds and creases; bleeding induced by minor trauma or abrasion
Generalized exfoliative, ulcerative, or bullous dermatitis
Death
––
Death
Skin necrosis or ulceration of full thickness dermis; spontaneous bleeding from involved site
Death
Remark: Rash/desquamation may be used for graft-versus-host disease.
RADIOTHERAPY IN PLEURAL MALIGNANT MESOTHELIOMA: WHY NOT! IN REGARD TO SCORSETTI ET AL. (INT J RADIAT ONCOL BIOL PHYS 2010;77:942–949); KRAYENBUEHL ET AL. (INT J RADIAT ONCOL BIOL PHYS 2010;78:628–634) To the Editor: We read with interest the articles by Scorsetti et al. (1) and Krayenbueh et al. (2). Although the improving technology allows a better target coverage and a dose sparing to organs at risk in pleural malignant mesothelioma (PMM), we believe that physiopathological bases that should support a role of radiotherapy (RT) in PMM are very weak. Regarding post pleurectomy/decortication (P/D) RT, the target volume includes the entire visceral and parietal pleura of the lung. These structures form a circumferential envelope around the lung, extend along fissures between the lobes, and are attached to ipsilateral pericardial and diaphragmatic surfaces. Although we can use sophisticated techniques to save the dose-limiting organs, the irradiation of the circumferential envelope around the lung—even if one manages to save the underlying pulmonary parenchyma—leads to fibrosis of the thoracic cage and of the lung envelope itself with a reduction in its own elasticity. This fact reduces pulmonary excursion and oxygenation, and alters the perfusion/ventilation ratio (P/V). Thus, the oxygenated blood from the contralateral healthy lung is desaturated by the venous-arterial shunt. This is a damage functionally greater than the one provoked by pneumonectomy: the removal of both parenchyma and vascular circulation avoids this shunt effect. Regarding RT after extrapleural pneumonectomy (EPP), EPP seems to have the advantages of removing the ipsilateral radiation dose-limiting lung, but it changes the natural history of the tumour, hindering the effectiveness of an adjuvant local treatment. Indeed, EPP halves local failures (from 63% of P/D to 31% of EPP), but, at the same time, doubles distant metastases (EPP 66% vs. P/D 35%), especially in abdominal (39% EPP vs. P/D 21%) and contralateral (22% EPP vs. P/D 11%) sites (3). This is probably because of the interruption of natural barriers (e.g., diaphragm) and the resulting postsurgical fluids flow (with cancer cells) into these compartments. So, although the studies with dose escalation to the hemithorax show an increasing local control (LC) (from 35% (4) to 13% (5) local failures), overall survival seems to worsen compared with P/D, even when surgery-related deaths are excluded (3). Probably the complexity of the region from a radiotherapeutic viewpoint and the introduction in clinical practice of more effective systemic adjuvant therapies will reduce the role of radiotherapy just as it happened with
ovarian cancer, which shares with PMM the tendency to spread along mesothelial lining. ELVIO G. RUSSI, M.D. Department of Radiation Oncology of Santa Croce General Hospital Cuneo, Italy GIANMAURO NUMICO, M.D. Department of Medical Oncology, Parini General Hospital Aosta, Italy UMBERTO RICARDI, M.D. Department of Radiation Oncology of University of Turin Turin, Italy doi:10.1016/j.ijrobp.2010.10.049 1. Scorsetti M, Bignardi M, Clivio A, et al. Volumetric modulation arc radiotherapy compared with static gantry intensity-modulated radiotherapy for malignant pleural mesothelioma tumor: A feasibility study. Int J Radiat Oncol Biol Phys 2010;77:942–949. 2. Krayenbuehl J, Hartmann M, Lomax AJ, et al. Proton therapy for malignant pleural mesothelioma after extrapleural pleuropneumonectomy. Int J Radiat Oncol Biol Phys 2010;78:628–634. 3. Flores RM, Pass HI, Seshan VE, et al. Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: Results in 663 patients. J Thorac Cardiovas Surg 2008;135:620–626. e3. 4. Baldini M, Recht M, Strauss M, et al. Patterns of failure after trimodality therapy for malignant pleural mesothelioma. Ann Thorac Surg 1997;63:334–338. 5. Rice DC, Stevens CW, Correa AM, et al. Outcomes after extrapleural pneumonectomy and intensity-modulated radiation therapy for malignant pleural mesothelioma. Ann Thorac Surg 2007;84:1685–1693.
IN RESPONSE TO DR. RUSSI AND COLLEAGUES To the Editor: Single modality therapies in the treatment of malignant pleural mesothelioma (MPM) have generally failed to prolong patient survival; as a result, multimodality treatment regimens have been developed (1).
LETTERS TO THE EDITOR 2. Potthoff K, Hofheinz R, Hassel JC, et al. Interdisciplinary management of EGFR-inhibitor-induced skin reactions: a German expert opinion. Ann Oncol 2010. Available at: http://www.ncbi.nlm.nih.gov.bvs.cilea.it/ pubmed/20709812 [accessed September 2, 2010]. 3. Merlano M, Russi E, Benasso M, et al. Cisplatin-based chemoradiation plus cetuximab in locally advanced head and neck cancer: A phase II clinical study. Ann Oncol 2010. Available at: http://annonc.oxfordjournals. org/content/early/2010/09/01/annonc.mdq412.abstract.html?ijkey=eud MvoKseHjz1pz&keytype=ref [accessed September 2, 2010]. 4. Su X, Lacouture ME, Jia Y, et al. Risk of high-grade skin rash in cancer patients treated with cetuximab—an antibody against epidermal growth factor receptor: Systemic review and meta-analysis. Oncology 2009;77:124–133. 5. US Department of Health and Human Services, National Institutes of Health National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) and Common Toxicity Criteria (CTC) v. 4. 2009. Available at: http://evs.nci.nih.gov/ftp1/CTCAE/About.html [accessed July 10, 2010]. 6. Lacouture ME, Maitland ML, Segaert S, et al. A proposed EGFR inhibitor dermatologic adverse event-specific grading scale from the MASCC skin toxicity study group. Support Care Cancer 2010;18:509–522. 7. Pastore S, Mascia F, Mariani V, et al. The epidermal growth factor receptor system in skin repair and inflammation. J Invest Dermatol 2008;128 (6):1365–1374. 8. Budach W, Bolke E, Homey B. Severe cutaneous reaction during radiation therapy with concurrent cetuximab. N Engl J Med 2007;357:514–515. 9. B€olke E, Gerber PA, Lammering G, et al. Development and management of severe cutaneous side effects in head-and-neck cancer patients during concurrent radiotherapy and cetuximab. Strahlenther Onkol 2008;184: 105–110.
CETUXIMAB-RELATED RADIATION DERMATITIS IN HEAD-AND-NECK CANCER PATIENTS: IN REGARD TO STUDER ET AL. (INT J RADIAT ONCOL BIOL PHYS IN PRESS) To the Editor: We read with interest the paper by Studer et al. (1). The authors raise an important point: the absence of a specific and useful grading system to assess cetuximab-related radiation dermatitis (CrRD). In fact, there is too much subjectivity in using two scales of grading—as the authors did—to define the severity of this toxicity. So, although their conclusions may be correct, their objectivation is weak. The authors used two of three scales described in NCI Common Toxicity Criteria for Adverse Events grading system v. 3 (CTCAEv3), usually adopted in literature (2, 3) to describe cetuximab skin toxicity: 1) skin rash (SR), 2) acneiform rash (AR), and 3) radiation dermatitis (RD). These scales are often used singly or ‘‘in mixed form.’’ This fact can explain the variability of nomenclature and of incidence of Grade 3-4 toxicity reported by the literature (1). Studer states in the Discussion section: ‘‘This may in part result from nonspecific dermatitis grading systems (CTCAE, RTOG/EORTC), used to assess cetuximabrelated dermal changes’’ and Su (4), in a review of cetuximab toxicity, stressed ‘‘.the imperfection of NCI-CTC grading criteria, which may fail to reflect the clinical situation.’’ Indeed, the more recent CTCAE v.4 (5) and MASCC (Multinational Association for Supportive Care in Cancer) skin toxicity proposal (6) introduce some improvements, but the issue of the ‘‘in-field toxicity,’’ in our opinion, did not receive enough attention. Although RD is adequate to describe radiation toxicity, it is not suitable to describe the complex clinical aspect of CrRD. Actually, the two treatments may interfere each other with supra-additive effect because of the interference of cetuximab on reparative reaction induced by radiation, and additive effect, because of the sum of the two distinct toxicities: RD (i.e., erythema, dry and moist desquamation, and necrosis) and cetuximab toxicity (i.e., xerosis, inflammatory reaction (7), and folliculitis). This gives a different meaning to the classical RD signs: the thin, painless scurf of the dry desquamation, in the context of xerotic and inflamed dermis of CrRD, becomes thick, hurting, and painful scales. Moreover, the full thickness necrosis (well described by Budach et al. (8)) rapidly heals without disfiguring scar (9): can this have the same clinical meaning of RD necrosis? Perhaps we need to give more importance to in-field CrCD than it has been given so far (2, 6), by defining a specific scoring system, that leaves behind RD and defines a new scale, that takes into account what we have learned in the last years.
IN RESPONSE TO DR. RUSSI AND COLLEAGUES To the Editor: We thank Dr. Russi and colleagues for their interest in our publication. We agree that clear and objective nomenclature for grading cetuximab-related radiation dermatitis (CrRD) is lacking, and this point was clearly made in our discussion. However, we wish to clarify the manner in which we graded radiation dermatitis in our patient cohort. The assertion that we used two of the three scales described in the NCI Common Toxicity Criteria for Adverse Events v. 3 (CTCAEv3) to evaluate radiation dermatitis is incorrect, or perhaps a misinterpretation of our methodology. We used the ‘‘rash: dermatitis associated with radiation’’ scale alone and not either of the ‘‘rash: acne/ acneiform’’ or ‘‘rash/desquamation’’ scales (Table 1). In addition, we grouped Grade 3 and Grade 4 dermatitis together for the purpose of our analysis because we consider both toxicity grades to be clinically significant. The radiation dermatitis scale was used in a consistent manner to assess radiation toxicity in our patient population, for both the cetuximab and cisplatin groups. As a result, we feel that our results are as robust and objective as other published series. We acknowledge in our discussion that comparison of data from other centers is limited when different toxicity scales or definitions of CrRD are used. In addition, our use of bolus may be more frequent, and our results demonstrating an association between increased incidence of dermatitis and use of bolus may partly explain the higher incidence of CrRD in our patient population. Until a more uniform and universally accepted nomenclature is in use, we recommend that institutions use one grading scale in a consistent manner and that patients with extensive areas of bolus material be carefully monitored for acute skin toxicity.
ELVIO G. RUSSI, M.D. Department of Radiation Oncology Santa Croce General Hospital Cuneo, Italy GIANMAURO NUMICO, M.D. Department of Medical Oncology University of Parini Hospital Aosta, Italy MARCO C. MERLANO, M.D. Department of Medical Oncology Santa Croce General Hospital Cuneo, Italy CARMINE PINTO, M.D. Medical Oncology Unit S. Orsola-Malpighi Hospital Bologna, Italy doi:10.1016/j.ijrobp.2010.10.047
GABRIELA STUDER, M.D. MICHELLE BROWN, M.D. CHRISTOPH GLANZMANN, M.D. Department of Radiation Oncology University Hospital Zurich Zurich, Switzerland
1. Studer G, Brown M, Salgueiro EB, et al. Grade 3/4 dermatitis in head and neck cancer patients treated with concurrent cetuximab and IMRT. Int J Radiat Oncol Biol Phys 2010. Available at: http://www.redjournal.org/ search/quick [accessed August 28, 2010].
doi:10.1016/j.ijrobp.2010.10.045 1278
Letters to the Editor
1279
Table 1. NCI common toxicity criteria for adverse events v. 3 (CTCAEv3)
Rash/desquamation
Rash
Macular or papular eruption or erythema without associated symptoms
Macular or papular eruption or erythema with pruritus or other associated symptoms; localized desquamation or other lesions covering \50% of body surface area
Rash: acne/ acneiform
Acne
Intervention not indicated
Intervention indicated
Rash: dermatitis associated with radiation Select: Chemoradiation Radiation
Dermatitis Select
Faint erythema or dry desquamation
Moderate to brisk erythema; patchy moist desquamation, mostly confined to skin folds and creases; moderate edema
Severe, generalized erythroderma or macular, papular, or vesicular eruption; desquamation covering $50% body surface area Associated with pain, disfigurement, ulceration, or desquamation Moist desquamation other than skin folds and creases; bleeding induced by minor trauma or abrasion
Generalized exfoliative, ulcerative, or bullous dermatitis
Death
––
Death
Skin necrosis or ulceration of full thickness dermis; spontaneous bleeding from involved site
Death
Remark: Rash/desquamation may be used for graft-versus-host disease.
RADIOTHERAPY IN PLEURAL MALIGNANT MESOTHELIOMA: WHY NOT! IN REGARD TO SCORSETTI ET AL. (INT J RADIAT ONCOL BIOL PHYS 2010;77:942–949); KRAYENBUEHL ET AL. (INT J RADIAT ONCOL BIOL PHYS 2010;78:628–634) To the Editor: We read with interest the articles by Scorsetti et al. (1) and Krayenbueh et al. (2). Although the improving technology allows a better target coverage and a dose sparing to organs at risk in pleural malignant mesothelioma (PMM), we believe that physiopathological bases that should support a role of radiotherapy (RT) in PMM are very weak. Regarding post pleurectomy/decortication (P/D) RT, the target volume includes the entire visceral and parietal pleura of the lung. These structures form a circumferential envelope around the lung, extend along fissures between the lobes, and are attached to ipsilateral pericardial and diaphragmatic surfaces. Although we can use sophisticated techniques to save the dose-limiting organs, the irradiation of the circumferential envelope around the lung—even if one manages to save the underlying pulmonary parenchyma—leads to fibrosis of the thoracic cage and of the lung envelope itself with a reduction in its own elasticity. This fact reduces pulmonary excursion and oxygenation, and alters the perfusion/ventilation ratio (P/V). Thus, the oxygenated blood from the contralateral healthy lung is desaturated by the venous-arterial shunt. This is a damage functionally greater than the one provoked by pneumonectomy: the removal of both parenchyma and vascular circulation avoids this shunt effect. Regarding RT after extrapleural pneumonectomy (EPP), EPP seems to have the advantages of removing the ipsilateral radiation dose-limiting lung, but it changes the natural history of the tumour, hindering the effectiveness of an adjuvant local treatment. Indeed, EPP halves local failures (from 63% of P/D to 31% of EPP), but, at the same time, doubles distant metastases (EPP 66% vs. P/D 35%), especially in abdominal (39% EPP vs. P/D 21%) and contralateral (22% EPP vs. P/D 11%) sites (3). This is probably because of the interruption of natural barriers (e.g., diaphragm) and the resulting postsurgical fluids flow (with cancer cells) into these compartments. So, although the studies with dose escalation to the hemithorax show an increasing local control (LC) (from 35% (4) to 13% (5) local failures), overall survival seems to worsen compared with P/D, even when surgery-related deaths are excluded (3). Probably the complexity of the region from a radiotherapeutic viewpoint and the introduction in clinical practice of more effective systemic adjuvant therapies will reduce the role of radiotherapy just as it happened with
ovarian cancer, which shares with PMM the tendency to spread along mesothelial lining. ELVIO G. RUSSI, M.D. Department of Radiation Oncology of Santa Croce General Hospital Cuneo, Italy GIANMAURO NUMICO, M.D. Department of Medical Oncology, Parini General Hospital Aosta, Italy UMBERTO RICARDI, M.D. Department of Radiation Oncology of University of Turin Turin, Italy doi:10.1016/j.ijrobp.2010.10.049 1. Scorsetti M, Bignardi M, Clivio A, et al. Volumetric modulation arc radiotherapy compared with static gantry intensity-modulated radiotherapy for malignant pleural mesothelioma tumor: A feasibility study. Int J Radiat Oncol Biol Phys 2010;77:942–949. 2. Krayenbuehl J, Hartmann M, Lomax AJ, et al. Proton therapy for malignant pleural mesothelioma after extrapleural pleuropneumonectomy. Int J Radiat Oncol Biol Phys 2010;78:628–634. 3. Flores RM, Pass HI, Seshan VE, et al. Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: Results in 663 patients. J Thorac Cardiovas Surg 2008;135:620–626. e3. 4. Baldini M, Recht M, Strauss M, et al. Patterns of failure after trimodality therapy for malignant pleural mesothelioma. Ann Thorac Surg 1997;63:334–338. 5. Rice DC, Stevens CW, Correa AM, et al. Outcomes after extrapleural pneumonectomy and intensity-modulated radiation therapy for malignant pleural mesothelioma. Ann Thorac Surg 2007;84:1685–1693.
IN RESPONSE TO DR. RUSSI AND COLLEAGUES To the Editor: Single modality therapies in the treatment of malignant pleural mesothelioma (MPM) have generally failed to prolong patient survival; as a result, multimodality treatment regimens have been developed (1).