Stereotactic ablative radiotherapy (SABR) as primary, adjuvant, consolidation and re-treatment option in pancreatic cancer: scope for dose escalation and lessons for toxicity
Abstract Background Stereotactic ablative radiotherapy (SABR) offers an alternative treatment for pancreatic cancer, with the potential for improved tumour control and reduced toxicity compared with conventional therapies. However, optimal dose planning and delivery strategies are unelucidated and g...
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| Format: | Article |
| Language: | English |
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BMC
2018-10-01
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| Series: | Radiation Oncology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13014-018-1138-3 |
| _version_ | 1819106596498702336 |
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| author | Christy Goldsmith P. Nicholas Plowman Melanie M. Green Roger G. Dale Patricia M. Price |
| author_facet | Christy Goldsmith P. Nicholas Plowman Melanie M. Green Roger G. Dale Patricia M. Price |
| author_sort | Christy Goldsmith |
| collection | DOAJ |
| description | Abstract Background Stereotactic ablative radiotherapy (SABR) offers an alternative treatment for pancreatic cancer, with the potential for improved tumour control and reduced toxicity compared with conventional therapies. However, optimal dose planning and delivery strategies are unelucidated and gastro-intestinal (GI) toxicity remains a key concern. Methods Patients with inoperable non-metastatic pancreatic cancer who received CyberKnife® SABR (18–36 Gy) in three fractions as primary, adjuvant, consolidation or re-treatment options were studied. Patient individualised planning and delivery variables were collected and their impact on patient outcome examined. Linear-quadratic (LQ) radiobiology modelling methods were applied to assess SABR parameters against a conventional fractionated radiotherapy schedule. Results In total 42 patients were included, 37 (88%) of whom had stage T4 disease. SABR was used > 6 months post-primary therapy to re-treat residual disease in 11 (26.2%) patients and relapsed disease in nine (21.4%) patients. SABR was an adjuvant to other primary therapy for 14 (33.3%) patients and was the sole primary therapy for eight (19.0%) patients. The mean (95% CI) planning target volume (PTV), prescription isodose, percentage cover, minimum dose to PTV and biological effective dose (BED) were 76.3(63.8–88.7) cc, 67.3(65.2–69.5)%, 96.6(95.5–97.7)%, 22.3(21.0–23.6) Gy and 50.3(47.7–53.0) Gy, respectively. Only 3/37 (8.1%) patients experienced Grade 3 acute toxicities. Two (4.8%) patients converted to resectable status and median freedom-from-local-progression (FFLP) and overall survival (OS) were 9.8 and 8.4 months, respectively. No late toxicity was experienced in 27/32 (84.4%) patients; however, four (12.5%) patients — of whom two had particularly large PTV, two had sub-optimal number of fiducials and three breached organ-at-risk (OAR) constraints—showed Grade 4 duodenal toxicities. Longer delivery time, extended treatment course and reduced percentage coverage additionally associated with late toxicity, likely reflecting parameters typically applied to riskier patients. Larger PTV size and longer treatment course associated with OS. Comparator regimen LQ modelling analysis indicated 50% of patients received minimum PTV doses less potent than a conventional radiotherapy regimen, indicating scope for dose escalation. Conclusion The results demonstrate the value of SABR for a range of indications in pancreatic cancer. Dose escalation to increase BED may improve FFLP and OS in inoperable, non-metastatic disease: however concomitant enhanced stringency for duodenal protection is critical, particularly for patients where SABR is more challenging. |
| first_indexed | 2024-12-22T02:40:39Z |
| format | Article |
| id | doaj.art-e4364e6faecf4c819369794a01cb657e |
| institution | Directory Open Access Journal |
| issn | 1748-717X |
| language | English |
| last_indexed | 2024-12-22T02:40:39Z |
| publishDate | 2018-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Radiation Oncology |
| spelling | doaj.art-e4364e6faecf4c819369794a01cb657e2022-12-21T18:41:40ZengBMCRadiation Oncology1748-717X2018-10-0113111210.1186/s13014-018-1138-3Stereotactic ablative radiotherapy (SABR) as primary, adjuvant, consolidation and re-treatment option in pancreatic cancer: scope for dose escalation and lessons for toxicityChristy Goldsmith0P. Nicholas Plowman1Melanie M. Green2Roger G. Dale3Patricia M. Price4Guys and St Thomas’ NHS Foundation TrustThe London CyberKnife Centre, The Harley Street ClinicDepartment of Surgery and Cancer, Imperial College LondonDepartment of Surgery and Cancer, Imperial College LondonThe London CyberKnife Centre, The Harley Street ClinicAbstract Background Stereotactic ablative radiotherapy (SABR) offers an alternative treatment for pancreatic cancer, with the potential for improved tumour control and reduced toxicity compared with conventional therapies. However, optimal dose planning and delivery strategies are unelucidated and gastro-intestinal (GI) toxicity remains a key concern. Methods Patients with inoperable non-metastatic pancreatic cancer who received CyberKnife® SABR (18–36 Gy) in three fractions as primary, adjuvant, consolidation or re-treatment options were studied. Patient individualised planning and delivery variables were collected and their impact on patient outcome examined. Linear-quadratic (LQ) radiobiology modelling methods were applied to assess SABR parameters against a conventional fractionated radiotherapy schedule. Results In total 42 patients were included, 37 (88%) of whom had stage T4 disease. SABR was used > 6 months post-primary therapy to re-treat residual disease in 11 (26.2%) patients and relapsed disease in nine (21.4%) patients. SABR was an adjuvant to other primary therapy for 14 (33.3%) patients and was the sole primary therapy for eight (19.0%) patients. The mean (95% CI) planning target volume (PTV), prescription isodose, percentage cover, minimum dose to PTV and biological effective dose (BED) were 76.3(63.8–88.7) cc, 67.3(65.2–69.5)%, 96.6(95.5–97.7)%, 22.3(21.0–23.6) Gy and 50.3(47.7–53.0) Gy, respectively. Only 3/37 (8.1%) patients experienced Grade 3 acute toxicities. Two (4.8%) patients converted to resectable status and median freedom-from-local-progression (FFLP) and overall survival (OS) were 9.8 and 8.4 months, respectively. No late toxicity was experienced in 27/32 (84.4%) patients; however, four (12.5%) patients — of whom two had particularly large PTV, two had sub-optimal number of fiducials and three breached organ-at-risk (OAR) constraints—showed Grade 4 duodenal toxicities. Longer delivery time, extended treatment course and reduced percentage coverage additionally associated with late toxicity, likely reflecting parameters typically applied to riskier patients. Larger PTV size and longer treatment course associated with OS. Comparator regimen LQ modelling analysis indicated 50% of patients received minimum PTV doses less potent than a conventional radiotherapy regimen, indicating scope for dose escalation. Conclusion The results demonstrate the value of SABR for a range of indications in pancreatic cancer. Dose escalation to increase BED may improve FFLP and OS in inoperable, non-metastatic disease: however concomitant enhanced stringency for duodenal protection is critical, particularly for patients where SABR is more challenging.http://link.springer.com/article/10.1186/s13014-018-1138-3Stereotactic ablative radiotherapy (SABR)Cyberknife®Pancreatic cancerRadiobiologyDose escalationLocal control |
| spellingShingle | Christy Goldsmith P. Nicholas Plowman Melanie M. Green Roger G. Dale Patricia M. Price Stereotactic ablative radiotherapy (SABR) as primary, adjuvant, consolidation and re-treatment option in pancreatic cancer: scope for dose escalation and lessons for toxicity Radiation Oncology Stereotactic ablative radiotherapy (SABR) Cyberknife® Pancreatic cancer Radiobiology Dose escalation Local control |
| title | Stereotactic ablative radiotherapy (SABR) as primary, adjuvant, consolidation and re-treatment option in pancreatic cancer: scope for dose escalation and lessons for toxicity |
| title_full | Stereotactic ablative radiotherapy (SABR) as primary, adjuvant, consolidation and re-treatment option in pancreatic cancer: scope for dose escalation and lessons for toxicity |
| title_fullStr | Stereotactic ablative radiotherapy (SABR) as primary, adjuvant, consolidation and re-treatment option in pancreatic cancer: scope for dose escalation and lessons for toxicity |
| title_full_unstemmed | Stereotactic ablative radiotherapy (SABR) as primary, adjuvant, consolidation and re-treatment option in pancreatic cancer: scope for dose escalation and lessons for toxicity |
| title_short | Stereotactic ablative radiotherapy (SABR) as primary, adjuvant, consolidation and re-treatment option in pancreatic cancer: scope for dose escalation and lessons for toxicity |
| title_sort | stereotactic ablative radiotherapy sabr as primary adjuvant consolidation and re treatment option in pancreatic cancer scope for dose escalation and lessons for toxicity |
| topic | Stereotactic ablative radiotherapy (SABR) Cyberknife® Pancreatic cancer Radiobiology Dose escalation Local control |
| url | http://link.springer.com/article/10.1186/s13014-018-1138-3 |
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