Conversion of locally advanced to resectable pancreatic body cancer aided by phosphorus-32 brachytherapy (OncoSil)
View Article PDF
Prognosis for locally advanced pancreatic cancer (LAPC) patients remains poor. Conversion to resectability is infrequent with existing treatment strategies. Brachytherapy is a novel treatment option in this patient group.
Case report
A fit 75-year-old male developed abdominal pain in November 2020. Ultrasound reported a pancreatic mass. Computed tomography (CT) scan demonstrated a 25mm pancreatic body mass consistent with pancreatic adenocarcinoma (Figure 1) without biliary dilatation. Abnormal soft tissue extended into the coeliac axis and common hepatic artery. The mass abutted the splenoportal venous confluence. There were no distant metastases (cT4cN0cM0).
In the local upper-gastrointestinal MDM, the lesion was adjudged to be inoperable due to arterial involvement. Endoscopic ultrasound (EUS) biopsy confirmed moderately differentiated adenocarcinoma, strongly positive for s-100p. The patient consulted a medical oncologist. Palliative-intent chemotherapy was recommended. The option of brachytherapy was offered.
Treatment began with intravenous gemcitabine (1000mg/m[[2]]) and nab-paclitaxel (125mg/m[[2]]) on days 1, 8 and 15 in a 28-day cycle. After chemotherapy cycle one, OncoSil brachytherapy was administered using EUS on 10 February 2021, observing radiation-safe precautions. A tumour volume of 7.7ml was calculated from CT data with semi-automatic software (Intellispace Portal, Phillips Workstation). 4MBq (0.62ml) phosphorus-32 solution was injected via a 22G FNA needle.[[1]] Bremsstrahlung scan confirmed Oncosil placement (Figure 2).
CT after nine chemotherapy cycles demonstrated partial response[[2]]with separation from the coeliac artery (Figure 3).
Trial resection was offered. Surgery on 11 November 2021 confirmed sclerotic tumour in the pancreatic body without peritoneal or solid organ metastases. The coeliac axis and portal vein were tumour free. Peri-arterial tissue biopsy was negative for malignancy. Distal pancreatectomy with splenectomy was performed. Final histology showed a 17mm grade 2 adenocarcinoma with clear surgical margins. Lymph nodes were negative for cancer (ypT1ypN0).
Surgical recovery was uneventful. He completed three more chemotherapy cycles. Follow-up CT scans show no recurrent disease. He remains well 12 months after surgery.
Discussion
Despite improvements in treatment, pancreatic cancer has the lowest survival rate of all major cancers (8.2% 5-year survival).[[3]] Most patients are not candidates for curative-intent surgery due to locally advanced features (vascular invasion) or distant metastases. Prognosis for inoperable patients is poor with median survival <12 months. Treatment options for this group include chemotherapy alone, chemotherapy then chemoradiotherapy or stereotactic body radiotherapy. Resection of LAPC after chemoradiotherapy has been described, although R0 rates vary widely.[[4]]
Brachytherapy is a form of radiation therapy where a radiation source is implanted next to the area requiring treatment. The use of brachytherapy is established in selected solid organ tumours,[[5]] including prostate cancer,[[6]] but has not been hitherto widely adopted in pancreatic cancer. Implanted radiation damages tumour DNA, arresting cell proliferation and resulting in tumour ablation. OncoSil is a targeted radioactive isotope (phosphorus-32) designed for implantation directly into a pancreatic tumour via EUS. The delivery method provides more concentrated and localised beta radiation (100Gy[[1]]) compared to external beam radiation (typically around 40Gy[[7]]), reducing collateral toxicity.[[8]] The isotope is given concurrently with sensitising chemotherapy.
In one international pilot study including 50 patients with LAPC, 10 patients were able to have pancreaticoduodenctomy after OncoSil. R0 margins were achieved in eight. Six remained alive after 26.4–35.3 months follow-up. The safety profile was comparable with standard-of-care chemotherapy.[[9]]
OncoSil is a new therapeutic option for patients with LAPC in New Zealand. Conversion to operable disease has been observed overseas, providing the opportunity to improve the prognosis for this otherwise devastating disease. In New Zealand, one case of pancreatic head cancer has been resected with clear margins after OncoSil. One other case was found to be unresectable at laparotomy. To our knowledge this case is the first to describe the downstaging of locally advanced pancreatic body cancer to R0-resectable disease after brachytherapy in New Zealand.
Summary
Abstract
Aim
Method
Results
Conclusion
Author Information
Acknowledgements
Correspondence
Correspondence Email
Competing Interests
1) Bhutani MS, Kalpman JB, Tuli R, et al. An open-label, single-arm pilot study of EUS-guided brachytherapy with phosphorus-32 microparticles in combination with gemcitabine +/- nab-paclitaxel in unresectable locally advance pancreatic cancer (OncoPaC-1) Technical details and study protocol. Endosc Ultrasound. 2020;9(1):24-30.
2) Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247.
3) Arnold M, Rutherford MJ, Bardot A, et al. Progress in cancer survival, mortality, and incidence in seven high-income countries 1995-2014 (ICBP SURVMARK-2): a population-based study. Lancet Oncol. 2019:20(11):1439-1505.
4) Suker M, Beumer BR, Sadot E, et al. A patient-level meta-analysis of FOLFIRINOX for locally advanced pancreatic cancer. Lancet Oncol. 2016;17(6):801-810.
5) Lim KY, Kim D. Brachytherapy: A Comprehensive Review. Prog Med Phys. 2021;32(2):25-39.
6) Koukourakis G, Kelekis N, Armonis V, Kouloulias V. Brachytherapy for prostate cancer: a systematic review. Adv Urol. 2009;2009:327945. doi: 10.1155/2009/327945.
7) Blakaj A, Stein SM, Khan SA, Johung KL. Review and current state of radiation therapy for locally advanced pancreatic adenocarcinoma. J Gastrointest Oncol. 2018;9(6):1027-1036.
8) Cazacu IM, Singh BS, Saftoiu A, Bhutani MS. Endoscopic Ultrasound-Guided Treatment of Pancreatic Cancer. Curr Gastroenterol Rep. 2020;22(27). https://doi.org/10.1007/s11894-020-00767-1.
9) Ross PJ, Wasan HS, Croagh A, et al. Results of a single-arm pilot study of 32P microparticles in unresectable locally advanced pancreatic adenocarcinoma with gemcitabine/nab-paclitaxel or FOLFIRINOX Chemotherapy. EMSO Open. 2022;7(1):100356. http://doi.org/10.1016/j.esmoop.2021.100356.
For the PDF of this article,
contact nzmj@nzma.org.nz
Conversion of locally advanced to resectable pancreatic body cancer aided by phosphorus-32 brachytherapy (OncoSil)
View Article PDF
Prognosis for locally advanced pancreatic cancer (LAPC) patients remains poor. Conversion to resectability is infrequent with existing treatment strategies. Brachytherapy is a novel treatment option in this patient group.
Case report
A fit 75-year-old male developed abdominal pain in November 2020. Ultrasound reported a pancreatic mass. Computed tomography (CT) scan demonstrated a 25mm pancreatic body mass consistent with pancreatic adenocarcinoma (Figure 1) without biliary dilatation. Abnormal soft tissue extended into the coeliac axis and common hepatic artery. The mass abutted the splenoportal venous confluence. There were no distant metastases (cT4cN0cM0).
In the local upper-gastrointestinal MDM, the lesion was adjudged to be inoperable due to arterial involvement. Endoscopic ultrasound (EUS) biopsy confirmed moderately differentiated adenocarcinoma, strongly positive for s-100p. The patient consulted a medical oncologist. Palliative-intent chemotherapy was recommended. The option of brachytherapy was offered.
Treatment began with intravenous gemcitabine (1000mg/m[[2]]) and nab-paclitaxel (125mg/m[[2]]) on days 1, 8 and 15 in a 28-day cycle. After chemotherapy cycle one, OncoSil brachytherapy was administered using EUS on 10 February 2021, observing radiation-safe precautions. A tumour volume of 7.7ml was calculated from CT data with semi-automatic software (Intellispace Portal, Phillips Workstation). 4MBq (0.62ml) phosphorus-32 solution was injected via a 22G FNA needle.[[1]] Bremsstrahlung scan confirmed Oncosil placement (Figure 2).
CT after nine chemotherapy cycles demonstrated partial response[[2]]with separation from the coeliac artery (Figure 3).
Trial resection was offered. Surgery on 11 November 2021 confirmed sclerotic tumour in the pancreatic body without peritoneal or solid organ metastases. The coeliac axis and portal vein were tumour free. Peri-arterial tissue biopsy was negative for malignancy. Distal pancreatectomy with splenectomy was performed. Final histology showed a 17mm grade 2 adenocarcinoma with clear surgical margins. Lymph nodes were negative for cancer (ypT1ypN0).
Surgical recovery was uneventful. He completed three more chemotherapy cycles. Follow-up CT scans show no recurrent disease. He remains well 12 months after surgery.
Discussion
Despite improvements in treatment, pancreatic cancer has the lowest survival rate of all major cancers (8.2% 5-year survival).[[3]] Most patients are not candidates for curative-intent surgery due to locally advanced features (vascular invasion) or distant metastases. Prognosis for inoperable patients is poor with median survival <12 months. Treatment options for this group include chemotherapy alone, chemotherapy then chemoradiotherapy or stereotactic body radiotherapy. Resection of LAPC after chemoradiotherapy has been described, although R0 rates vary widely.[[4]]
Brachytherapy is a form of radiation therapy where a radiation source is implanted next to the area requiring treatment. The use of brachytherapy is established in selected solid organ tumours,[[5]] including prostate cancer,[[6]] but has not been hitherto widely adopted in pancreatic cancer. Implanted radiation damages tumour DNA, arresting cell proliferation and resulting in tumour ablation. OncoSil is a targeted radioactive isotope (phosphorus-32) designed for implantation directly into a pancreatic tumour via EUS. The delivery method provides more concentrated and localised beta radiation (100Gy[[1]]) compared to external beam radiation (typically around 40Gy[[7]]), reducing collateral toxicity.[[8]] The isotope is given concurrently with sensitising chemotherapy.
In one international pilot study including 50 patients with LAPC, 10 patients were able to have pancreaticoduodenctomy after OncoSil. R0 margins were achieved in eight. Six remained alive after 26.4–35.3 months follow-up. The safety profile was comparable with standard-of-care chemotherapy.[[9]]
OncoSil is a new therapeutic option for patients with LAPC in New Zealand. Conversion to operable disease has been observed overseas, providing the opportunity to improve the prognosis for this otherwise devastating disease. In New Zealand, one case of pancreatic head cancer has been resected with clear margins after OncoSil. One other case was found to be unresectable at laparotomy. To our knowledge this case is the first to describe the downstaging of locally advanced pancreatic body cancer to R0-resectable disease after brachytherapy in New Zealand.
Summary
Abstract
Aim
Method
Results
Conclusion
Author Information
Acknowledgements
Correspondence
Correspondence Email
Competing Interests
1) Bhutani MS, Kalpman JB, Tuli R, et al. An open-label, single-arm pilot study of EUS-guided brachytherapy with phosphorus-32 microparticles in combination with gemcitabine +/- nab-paclitaxel in unresectable locally advance pancreatic cancer (OncoPaC-1) Technical details and study protocol. Endosc Ultrasound. 2020;9(1):24-30.
2) Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247.
3) Arnold M, Rutherford MJ, Bardot A, et al. Progress in cancer survival, mortality, and incidence in seven high-income countries 1995-2014 (ICBP SURVMARK-2): a population-based study. Lancet Oncol. 2019:20(11):1439-1505.
4) Suker M, Beumer BR, Sadot E, et al. A patient-level meta-analysis of FOLFIRINOX for locally advanced pancreatic cancer. Lancet Oncol. 2016;17(6):801-810.
5) Lim KY, Kim D. Brachytherapy: A Comprehensive Review. Prog Med Phys. 2021;32(2):25-39.
6) Koukourakis G, Kelekis N, Armonis V, Kouloulias V. Brachytherapy for prostate cancer: a systematic review. Adv Urol. 2009;2009:327945. doi: 10.1155/2009/327945.
7) Blakaj A, Stein SM, Khan SA, Johung KL. Review and current state of radiation therapy for locally advanced pancreatic adenocarcinoma. J Gastrointest Oncol. 2018;9(6):1027-1036.
8) Cazacu IM, Singh BS, Saftoiu A, Bhutani MS. Endoscopic Ultrasound-Guided Treatment of Pancreatic Cancer. Curr Gastroenterol Rep. 2020;22(27). https://doi.org/10.1007/s11894-020-00767-1.
9) Ross PJ, Wasan HS, Croagh A, et al. Results of a single-arm pilot study of 32P microparticles in unresectable locally advanced pancreatic adenocarcinoma with gemcitabine/nab-paclitaxel or FOLFIRINOX Chemotherapy. EMSO Open. 2022;7(1):100356. http://doi.org/10.1016/j.esmoop.2021.100356.
For the PDF of this article,
contact nzmj@nzma.org.nz
Conversion of locally advanced to resectable pancreatic body cancer aided by phosphorus-32 brachytherapy (OncoSil)
View Article PDF
Prognosis for locally advanced pancreatic cancer (LAPC) patients remains poor. Conversion to resectability is infrequent with existing treatment strategies. Brachytherapy is a novel treatment option in this patient group.
Case report
A fit 75-year-old male developed abdominal pain in November 2020. Ultrasound reported a pancreatic mass. Computed tomography (CT) scan demonstrated a 25mm pancreatic body mass consistent with pancreatic adenocarcinoma (Figure 1) without biliary dilatation. Abnormal soft tissue extended into the coeliac axis and common hepatic artery. The mass abutted the splenoportal venous confluence. There were no distant metastases (cT4cN0cM0).
In the local upper-gastrointestinal MDM, the lesion was adjudged to be inoperable due to arterial involvement. Endoscopic ultrasound (EUS) biopsy confirmed moderately differentiated adenocarcinoma, strongly positive for s-100p. The patient consulted a medical oncologist. Palliative-intent chemotherapy was recommended. The option of brachytherapy was offered.
Treatment began with intravenous gemcitabine (1000mg/m[[2]]) and nab-paclitaxel (125mg/m[[2]]) on days 1, 8 and 15 in a 28-day cycle. After chemotherapy cycle one, OncoSil brachytherapy was administered using EUS on 10 February 2021, observing radiation-safe precautions. A tumour volume of 7.7ml was calculated from CT data with semi-automatic software (Intellispace Portal, Phillips Workstation). 4MBq (0.62ml) phosphorus-32 solution was injected via a 22G FNA needle.[[1]] Bremsstrahlung scan confirmed Oncosil placement (Figure 2).
CT after nine chemotherapy cycles demonstrated partial response[[2]]with separation from the coeliac artery (Figure 3).
Trial resection was offered. Surgery on 11 November 2021 confirmed sclerotic tumour in the pancreatic body without peritoneal or solid organ metastases. The coeliac axis and portal vein were tumour free. Peri-arterial tissue biopsy was negative for malignancy. Distal pancreatectomy with splenectomy was performed. Final histology showed a 17mm grade 2 adenocarcinoma with clear surgical margins. Lymph nodes were negative for cancer (ypT1ypN0).
Surgical recovery was uneventful. He completed three more chemotherapy cycles. Follow-up CT scans show no recurrent disease. He remains well 12 months after surgery.
Discussion
Despite improvements in treatment, pancreatic cancer has the lowest survival rate of all major cancers (8.2% 5-year survival).[[3]] Most patients are not candidates for curative-intent surgery due to locally advanced features (vascular invasion) or distant metastases. Prognosis for inoperable patients is poor with median survival <12 months. Treatment options for this group include chemotherapy alone, chemotherapy then chemoradiotherapy or stereotactic body radiotherapy. Resection of LAPC after chemoradiotherapy has been described, although R0 rates vary widely.[[4]]
Brachytherapy is a form of radiation therapy where a radiation source is implanted next to the area requiring treatment. The use of brachytherapy is established in selected solid organ tumours,[[5]] including prostate cancer,[[6]] but has not been hitherto widely adopted in pancreatic cancer. Implanted radiation damages tumour DNA, arresting cell proliferation and resulting in tumour ablation. OncoSil is a targeted radioactive isotope (phosphorus-32) designed for implantation directly into a pancreatic tumour via EUS. The delivery method provides more concentrated and localised beta radiation (100Gy[[1]]) compared to external beam radiation (typically around 40Gy[[7]]), reducing collateral toxicity.[[8]] The isotope is given concurrently with sensitising chemotherapy.
In one international pilot study including 50 patients with LAPC, 10 patients were able to have pancreaticoduodenctomy after OncoSil. R0 margins were achieved in eight. Six remained alive after 26.4–35.3 months follow-up. The safety profile was comparable with standard-of-care chemotherapy.[[9]]
OncoSil is a new therapeutic option for patients with LAPC in New Zealand. Conversion to operable disease has been observed overseas, providing the opportunity to improve the prognosis for this otherwise devastating disease. In New Zealand, one case of pancreatic head cancer has been resected with clear margins after OncoSil. One other case was found to be unresectable at laparotomy. To our knowledge this case is the first to describe the downstaging of locally advanced pancreatic body cancer to R0-resectable disease after brachytherapy in New Zealand.
Summary
Abstract
Aim
Method
Results
Conclusion
Author Information
Acknowledgements
Correspondence
Correspondence Email
Competing Interests
1) Bhutani MS, Kalpman JB, Tuli R, et al. An open-label, single-arm pilot study of EUS-guided brachytherapy with phosphorus-32 microparticles in combination with gemcitabine +/- nab-paclitaxel in unresectable locally advance pancreatic cancer (OncoPaC-1) Technical details and study protocol. Endosc Ultrasound. 2020;9(1):24-30.
2) Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247.
3) Arnold M, Rutherford MJ, Bardot A, et al. Progress in cancer survival, mortality, and incidence in seven high-income countries 1995-2014 (ICBP SURVMARK-2): a population-based study. Lancet Oncol. 2019:20(11):1439-1505.
4) Suker M, Beumer BR, Sadot E, et al. A patient-level meta-analysis of FOLFIRINOX for locally advanced pancreatic cancer. Lancet Oncol. 2016;17(6):801-810.
5) Lim KY, Kim D. Brachytherapy: A Comprehensive Review. Prog Med Phys. 2021;32(2):25-39.
6) Koukourakis G, Kelekis N, Armonis V, Kouloulias V. Brachytherapy for prostate cancer: a systematic review. Adv Urol. 2009;2009:327945. doi: 10.1155/2009/327945.
7) Blakaj A, Stein SM, Khan SA, Johung KL. Review and current state of radiation therapy for locally advanced pancreatic adenocarcinoma. J Gastrointest Oncol. 2018;9(6):1027-1036.
8) Cazacu IM, Singh BS, Saftoiu A, Bhutani MS. Endoscopic Ultrasound-Guided Treatment of Pancreatic Cancer. Curr Gastroenterol Rep. 2020;22(27). https://doi.org/10.1007/s11894-020-00767-1.
9) Ross PJ, Wasan HS, Croagh A, et al. Results of a single-arm pilot study of 32P microparticles in unresectable locally advanced pancreatic adenocarcinoma with gemcitabine/nab-paclitaxel or FOLFIRINOX Chemotherapy. EMSO Open. 2022;7(1):100356. http://doi.org/10.1016/j.esmoop.2021.100356.
Contact diana@nzma.org.nz
for the PDF of this article
Conversion of locally advanced to resectable pancreatic body cancer aided by phosphorus-32 brachytherapy (OncoSil)
Prognosis for locally advanced pancreatic cancer (LAPC) patients remains poor. Conversion to resectability is infrequent with existing treatment strategies. Brachytherapy is a novel treatment option in this patient group.
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