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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)
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).
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).