1446 M. Josipovic et al.
Deep inspiration breath hold radiotherapy of lung cancer: The good, the bad and the ugly case
MIRJANA JOSIPOVIC1, MARIANNE CAMILLE AZNAR1,2 & GITTE FREDBERG PERSSON1 1Department
of Oncology, Rigshospitalet, Copenhagen, Denmark and 2Copenhagen University, Niels Bohr Institute and Faculty of Health and Medical Sciences, Copenhagen, Denmark To the Editor, In definitive radiotherapy of locally advanced lung cancer, the lung dose constraints are often difficult to meet. In these cases treatment in deep inspiration breath hold (DIBH) is tempting, as the increased volume of the inflated lung enables fulfilment of the dose constraints [1,2]. However not all patients are suited for DIBH treatment. We present three cases that demonstrate the caveats of the DIBH strategy. Methods All three patients were referred for definitive radiotherapy of non-small cell lung cancer (NSCLC) with 66 Gy in 33 fractions. Due to failure to fulfil dose constraints for lung in free breathing [mean lung dose (MLD) ⬍ 20 Gy and lung volume receiving 20 Gy or more (V20) ⬍ 37%], the patients were re-planned in DIBH with visual guidance using Real-time Position ManagementTM (RPM) system (Varian® Medical Systems) [3]. Three-dimensional conformal technique was used for all plans. Orthogonal kV images in DIBH were used for daily image guidance. DIBH cone beam computed tomography (CBCT), requiring three DIBH of 20 seconds, was acquired at 10th and 20th fractions as quality control [4]. Results The “good” case Patient #1 had an unspecified NSCLC (T3N3M0) with two tumours in the right upper lobe and lymph node metastases in levels 4R and 4L. Dose distribution on a free breathing midventilation scan resulted in a MLD of 21.1 Gy and V20 of 40.5%. In DIBH the total lung volume increased by 67%, MLD decreased to 19.7 Gy and V20 to 35.8% (Figure 1). DIBH CBCTs showed reproducible tumour position
during DIBH, suggesting a safe and accurate delivery of the dose to the tumour on a daily basis. The “bad” case Patient #2 had a papillary adenocarcinoma (T3N3M0) with two tumours in the right lower lobe, intra bronchial tumour masses in the left main bronchus and mediastinal lymph node metastases in levels 4R, 4L and 7. DIBH increased lung volume by 66%, but moved the targets apart resulting in an increase as well as a separation of the planning target volume (PTV), increasing MLD from 21.2 Gy to 23.1 Gy and V20 from 40% to 49% in free breathing versus DIBH (Figure 2). Treatment was performed in free breathing. The “ugly” case Patient #3 had an 8 cm large adenocarcinoma (T3N3M0) in the right lower lobe and lymph node metastases in levels 4R and 4L. Lung volume increased 82% in DIBH, decreasing MLD from 25.4 Gy to 18.7 Gy and V20 from 42% to 32%. DIBH CBCT at 10th fraction revealed inter-fractional variation in caudal tumour position of ⬎ 1.5 cm, despite good reproducibility of the external surrogate signal (Figure 3). After this day, the DIBH level was adjusted daily to match the diaphragm position to its position on the treatment planning DIBH CT. Conclusion It is clear that not all NSCLC patients benefit from DIBH. Moreover, clinically significant uncertainties in DIBH reproducibility by means of external surrogate are present and daily setup to tumour is strongly recommended. We have started a feasibility
Correspondence: M. Josipovic, Department of Oncology 3994, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. Tel: ⫹ 45 3545 8987. Fax: ⫹ 45 3545 3990. E-mail: [email protected] (Received 9 April 2014 ; accepted 28 April 2014 ) ISSN 0284-186X print/ISSN 1651-226X online © 2014 Informa Healthcare DOI: 10.3109/0284186X.2014.922216
Deep inspiration breath hold radiotherapy of lung cancer 1447
Figure 1. Dose distribution on a free breathing midventilation scan (left side) resulted in MLD of 21.1 Gy and V20 of 40.5%.which exceeded the lung tissue constraints. Treatment plan on a DIBH scan (B right side) decreased MLD to 19.7 Gy and V20 to 35.8%. Lung volume increased by 67%.
Figure 2. The increased lung volume in DIBH moved the targets apart, increasing MLD and V20 in DIBH (right) compared to the free breathing (left) from 23.1 Gy to 21.2 Gy and from 49% to 40%, respectively.
Figure 3. A large mismatch of the caudal target of patient #3 on the 10th treatment day shown in split window of the planning CT (left) and CBCT (right) in coronal and sagittal views.
study to investigate in detail the uncertainties in visually guided DIBH RT of lung cancer and to find the optimal image guidance protocol for DIBH [5]. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References [1] Giraud P, Morvan E, Claude L, Mornex F, Le Pechoux C, Bachaud JM, et al. Respiratory gating techniques for optimization of lung cancer radiotherapy. J Thor Oncol 2011;6: 2058–68. [2] Rosenzweig KE, Hanley J, Mah D, Mageras G, Hunt M, Toner S, et al. The deep inspiration breath-hold technique in
1448 F. O. Larsen et al. the treatment of inoperable non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2000;1:81–7. [3] Keall PJ, Mageras GS, Balter J, Emery RS, Forster KM, Jiang SB, et al. The management of respiratory motion in radiation oncology. Report of AAPM Task Group 76. Med Phys 2006;33:3874–900. [4] Duggan DM, Ding GX, Coffey CW, Kirby W, Hallahan DE, Malcolm A, et al. Deep-inspiration breath-hold kilovoltage
cone-beam CT for setup of stereotactic body radiation therapy for lung tumors: Initial experience. Lung Cancer 2007;56: 77–88. [5] Josipovic M, Persson GF, Håkansson K, Damkjær SMS, Bangsgaard JP, Westman G, et al. Deep inspiration breath hold radiotherapy for locally advanced lung cancer: Comparison of different treatment techniques on target coverage, lung dose and treatment delivery time. Acta Oncol 2013;52:1582–6.
Gemcitabine, capecitabine and oxaliplatin in advanced biliary tract carcinoma
FINN OLE LARSEN1, ANNE HAAHR MELLERGAARD2, DAN TAKSONY SOLYOM HOEGDALL1 & LARS HENRIK JENSEN2 1Department
of Oncology, Herlev Hospital, University of Copenhagen, Denmark, and 2Department of Oncology, Vejle Hospital, University of Southern Denmark, Denmark
To the Editor, Biliary tract carcinoma includes gallbladder cancer and cholangiocarcinoma. Cholangiocarcinoma can be subdivided into intrahepatic, perihilar (Klatskin) and extrahepatic carcinoma. Biliary tract carcinoma is a relative rare cancer which account for less than 1% of new cancer cases. Only resection is a curative treatment, but unfortunately resection is only possible in approximately 10%, leaving most patients with advanced disease. For patients with advanced disease only palliative treatment is possible. The most active drugs in phase II trials are gemcitabine [1,2], flourpyrimidine/capecitabine [3,4] and cisplatin/oxaliplatin [5–9]. Support for gemcitabine as an anchor drug for the treatment of advanced biliary tract carcinoma comes from a pooled analysis of 104 trials that showed that the subgroup receiving a combination of gemcitabine and platinium-based agent had the greatest benefit [10]. In 2010 Valle published a study with 410 patients where cisplatin and gemcitabine were compared to gemcitabine alone [11]. The patients receiving cisplatin and gemcitabine had a better and impressive median overall survival (OS) of 11.7 months. Cisplatin and gemcitabine were therefore suggested as standard treatment to patients with advanced biliary tract carcinoma. Several phase two trials have replaced cisplatin with oxaliplatin and the combination with gemcitabine and oxaliplatin
show similar median OS of approximately 12 months [12,13]. One smaller trial tested the triplet of gemcitabine, oxaliplatin and capecitabine and found it well tolerated with similar median OS [14]. Furthermore, the study showed that the addition of capecitabine allowed a lower oxaliplatin dose than the usual 100 mg/m2 every second week and subsequently reducing especially neutropenia and neurotoxicity. In the present study we wanted to investigate the efficiency of the triplet gemcitabine, capecitabine and oxaliplatin in daily clinic and compare the results with other similar studies. Material and methods From January 2005 to January 2013, 194 patients from two institutions were evaluated retrospective. They were included if they had received a histo- or cytological diagnosis of non-resectable or recurrent biliary tract carcinoma. In cases with indeterminate but malignant histology, imaging should support the diagnosis and other primary tumors should be excluded. Location of the primary tumor could be intrahepatic, perihilar or extrahepatic bile ducts or in the gallbladder. All patients were evaluated nonresectable by liver surgeons. Patients in performance status 0, 1 or 2 were included if they had a bilirubin less than two times the upper limit of the normal range. Two different schedules were used. Capecitabine 650
Correspondence: F. O. Larsen, Department of Oncology, Herlev Hospital, Ringvejen 75, 2730 Herlev, Denmark. Tel: ⫹ 45 38682329. E-mail: finn.ole.larsen@ regionh.dk (Received 19 March 2014 ; accepted 13 May 2014 ) ISSN 0284-186X print/ISSN 1651-226X online © 2014 Informa Healthcare DOI: 10.3109/0284186X.2014.926026
Copyright of Acta Oncologica is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Deep inspiration breath hold radiotherapy of lung cancer: The good, the bad and the ugly case
MIRJANA JOSIPOVIC1, MARIANNE CAMILLE AZNAR1,2 & GITTE FREDBERG PERSSON1 1Department
of Oncology, Rigshospitalet, Copenhagen, Denmark and 2Copenhagen University, Niels Bohr Institute and Faculty of Health and Medical Sciences, Copenhagen, Denmark To the Editor, In definitive radiotherapy of locally advanced lung cancer, the lung dose constraints are often difficult to meet. In these cases treatment in deep inspiration breath hold (DIBH) is tempting, as the increased volume of the inflated lung enables fulfilment of the dose constraints [1,2]. However not all patients are suited for DIBH treatment. We present three cases that demonstrate the caveats of the DIBH strategy. Methods All three patients were referred for definitive radiotherapy of non-small cell lung cancer (NSCLC) with 66 Gy in 33 fractions. Due to failure to fulfil dose constraints for lung in free breathing [mean lung dose (MLD) ⬍ 20 Gy and lung volume receiving 20 Gy or more (V20) ⬍ 37%], the patients were re-planned in DIBH with visual guidance using Real-time Position ManagementTM (RPM) system (Varian® Medical Systems) [3]. Three-dimensional conformal technique was used for all plans. Orthogonal kV images in DIBH were used for daily image guidance. DIBH cone beam computed tomography (CBCT), requiring three DIBH of 20 seconds, was acquired at 10th and 20th fractions as quality control [4]. Results The “good” case Patient #1 had an unspecified NSCLC (T3N3M0) with two tumours in the right upper lobe and lymph node metastases in levels 4R and 4L. Dose distribution on a free breathing midventilation scan resulted in a MLD of 21.1 Gy and V20 of 40.5%. In DIBH the total lung volume increased by 67%, MLD decreased to 19.7 Gy and V20 to 35.8% (Figure 1). DIBH CBCTs showed reproducible tumour position
during DIBH, suggesting a safe and accurate delivery of the dose to the tumour on a daily basis. The “bad” case Patient #2 had a papillary adenocarcinoma (T3N3M0) with two tumours in the right lower lobe, intra bronchial tumour masses in the left main bronchus and mediastinal lymph node metastases in levels 4R, 4L and 7. DIBH increased lung volume by 66%, but moved the targets apart resulting in an increase as well as a separation of the planning target volume (PTV), increasing MLD from 21.2 Gy to 23.1 Gy and V20 from 40% to 49% in free breathing versus DIBH (Figure 2). Treatment was performed in free breathing. The “ugly” case Patient #3 had an 8 cm large adenocarcinoma (T3N3M0) in the right lower lobe and lymph node metastases in levels 4R and 4L. Lung volume increased 82% in DIBH, decreasing MLD from 25.4 Gy to 18.7 Gy and V20 from 42% to 32%. DIBH CBCT at 10th fraction revealed inter-fractional variation in caudal tumour position of ⬎ 1.5 cm, despite good reproducibility of the external surrogate signal (Figure 3). After this day, the DIBH level was adjusted daily to match the diaphragm position to its position on the treatment planning DIBH CT. Conclusion It is clear that not all NSCLC patients benefit from DIBH. Moreover, clinically significant uncertainties in DIBH reproducibility by means of external surrogate are present and daily setup to tumour is strongly recommended. We have started a feasibility
Correspondence: M. Josipovic, Department of Oncology 3994, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. Tel: ⫹ 45 3545 8987. Fax: ⫹ 45 3545 3990. E-mail: [email protected] (Received 9 April 2014 ; accepted 28 April 2014 ) ISSN 0284-186X print/ISSN 1651-226X online © 2014 Informa Healthcare DOI: 10.3109/0284186X.2014.922216
Deep inspiration breath hold radiotherapy of lung cancer 1447
Figure 1. Dose distribution on a free breathing midventilation scan (left side) resulted in MLD of 21.1 Gy and V20 of 40.5%.which exceeded the lung tissue constraints. Treatment plan on a DIBH scan (B right side) decreased MLD to 19.7 Gy and V20 to 35.8%. Lung volume increased by 67%.
Figure 2. The increased lung volume in DIBH moved the targets apart, increasing MLD and V20 in DIBH (right) compared to the free breathing (left) from 23.1 Gy to 21.2 Gy and from 49% to 40%, respectively.
Figure 3. A large mismatch of the caudal target of patient #3 on the 10th treatment day shown in split window of the planning CT (left) and CBCT (right) in coronal and sagittal views.
study to investigate in detail the uncertainties in visually guided DIBH RT of lung cancer and to find the optimal image guidance protocol for DIBH [5]. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References [1] Giraud P, Morvan E, Claude L, Mornex F, Le Pechoux C, Bachaud JM, et al. Respiratory gating techniques for optimization of lung cancer radiotherapy. J Thor Oncol 2011;6: 2058–68. [2] Rosenzweig KE, Hanley J, Mah D, Mageras G, Hunt M, Toner S, et al. The deep inspiration breath-hold technique in
1448 F. O. Larsen et al. the treatment of inoperable non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2000;1:81–7. [3] Keall PJ, Mageras GS, Balter J, Emery RS, Forster KM, Jiang SB, et al. The management of respiratory motion in radiation oncology. Report of AAPM Task Group 76. Med Phys 2006;33:3874–900. [4] Duggan DM, Ding GX, Coffey CW, Kirby W, Hallahan DE, Malcolm A, et al. Deep-inspiration breath-hold kilovoltage
cone-beam CT for setup of stereotactic body radiation therapy for lung tumors: Initial experience. Lung Cancer 2007;56: 77–88. [5] Josipovic M, Persson GF, Håkansson K, Damkjær SMS, Bangsgaard JP, Westman G, et al. Deep inspiration breath hold radiotherapy for locally advanced lung cancer: Comparison of different treatment techniques on target coverage, lung dose and treatment delivery time. Acta Oncol 2013;52:1582–6.
Gemcitabine, capecitabine and oxaliplatin in advanced biliary tract carcinoma
FINN OLE LARSEN1, ANNE HAAHR MELLERGAARD2, DAN TAKSONY SOLYOM HOEGDALL1 & LARS HENRIK JENSEN2 1Department
of Oncology, Herlev Hospital, University of Copenhagen, Denmark, and 2Department of Oncology, Vejle Hospital, University of Southern Denmark, Denmark
To the Editor, Biliary tract carcinoma includes gallbladder cancer and cholangiocarcinoma. Cholangiocarcinoma can be subdivided into intrahepatic, perihilar (Klatskin) and extrahepatic carcinoma. Biliary tract carcinoma is a relative rare cancer which account for less than 1% of new cancer cases. Only resection is a curative treatment, but unfortunately resection is only possible in approximately 10%, leaving most patients with advanced disease. For patients with advanced disease only palliative treatment is possible. The most active drugs in phase II trials are gemcitabine [1,2], flourpyrimidine/capecitabine [3,4] and cisplatin/oxaliplatin [5–9]. Support for gemcitabine as an anchor drug for the treatment of advanced biliary tract carcinoma comes from a pooled analysis of 104 trials that showed that the subgroup receiving a combination of gemcitabine and platinium-based agent had the greatest benefit [10]. In 2010 Valle published a study with 410 patients where cisplatin and gemcitabine were compared to gemcitabine alone [11]. The patients receiving cisplatin and gemcitabine had a better and impressive median overall survival (OS) of 11.7 months. Cisplatin and gemcitabine were therefore suggested as standard treatment to patients with advanced biliary tract carcinoma. Several phase two trials have replaced cisplatin with oxaliplatin and the combination with gemcitabine and oxaliplatin
show similar median OS of approximately 12 months [12,13]. One smaller trial tested the triplet of gemcitabine, oxaliplatin and capecitabine and found it well tolerated with similar median OS [14]. Furthermore, the study showed that the addition of capecitabine allowed a lower oxaliplatin dose than the usual 100 mg/m2 every second week and subsequently reducing especially neutropenia and neurotoxicity. In the present study we wanted to investigate the efficiency of the triplet gemcitabine, capecitabine and oxaliplatin in daily clinic and compare the results with other similar studies. Material and methods From January 2005 to January 2013, 194 patients from two institutions were evaluated retrospective. They were included if they had received a histo- or cytological diagnosis of non-resectable or recurrent biliary tract carcinoma. In cases with indeterminate but malignant histology, imaging should support the diagnosis and other primary tumors should be excluded. Location of the primary tumor could be intrahepatic, perihilar or extrahepatic bile ducts or in the gallbladder. All patients were evaluated nonresectable by liver surgeons. Patients in performance status 0, 1 or 2 were included if they had a bilirubin less than two times the upper limit of the normal range. Two different schedules were used. Capecitabine 650
Correspondence: F. O. Larsen, Department of Oncology, Herlev Hospital, Ringvejen 75, 2730 Herlev, Denmark. Tel: ⫹ 45 38682329. E-mail: finn.ole.larsen@ regionh.dk (Received 19 March 2014 ; accepted 13 May 2014 ) ISSN 0284-186X print/ISSN 1651-226X online © 2014 Informa Healthcare DOI: 10.3109/0284186X.2014.926026
Copyright of Acta Oncologica is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
