Phosphorus-32 Research Articles

1308P Comparison of tumour size on outcomes for patients with unresectable locally advanced pancreatic adenocarcinoma (LAPC) receiving P-32 microparticles with standard-of-care chemotherapy (SoC CT)

Unresectable LAPC (uLAPC) has a poor prognosis. SoC is CT or chemoradiotherapy. Brachytherapy enables beta radiation emitting Phosphorus-32 (P-32) microparticles to be implanted into pancreatic tumours via endoscopic ultrasound (EUS) guidance. We report a post hoc analysis of tumour size in PanCO, a single-arm, multicentre study of P-32 microparticles with SoC CT in uLAPC.

Evaluation of Long-Term Outcomes and Toxicity After Stereotactic Phosphorus-32–Based Intracavitary Brachytherapy in Patients With Cystic Craniopharyngioma

Interstitial brachytherapy based on phosphorus-32 (P-32) has an established role as a minimally invasive treatment modality for patients with cystic craniopharyngioma. However, reporting on long-term outcomes with toxicity profiles for large cohorts is lacking in the literature. The purpose of this study is therefore to evaluate the long-term visual, endocrinal, and neurocognitive functions in what is the largest patient series having received this treatment to date. We retrospectively evaluated 90 patients with cystic craniopharyngiomas who were treated with stereotactic intracavitary brachytherapy between 1998 and 2010. Colloidal activity of injected radioisotope P-32 was based on an even distribution within the tumor. After treatment, patients were followed-up for a minimum of 5 years and over a mean of 121 months (60-192 months) to assess radiographic and clinical responses. The 90 patients included in our study cohort underwent a total of 108 stereotactic surgical procedures for 129 craniopharyngioma-related cysts. Of the included tumors, 65 (72.2%) were associated with a single cyst, 15 (16.7%) were associated with 2 cysts, and 10 (11.1%) tumors had developed septations with 3 to 4 cysts. Stereotactic cyst puncture and content aspiration were used to drain a mean cyst fluid volume of 21.4 mL (1.0-55.0 mL). Each cyst was then instilled for interstitial brachytherapy with colloidal P-32 solution. Based on radiographic follow-up assessments, 56 cysts (43.4%) showed resolution and/or nonrecurrence, which was classified as a complete response to treatment; 47 cysts (36.4%) showed a partial response; and 5 cysts (3.9%) displayed a stable appearance. Treatment resulted in immediate and clinically significant vision improvement in 54 of 63 (86%) symptomatic patients, and this improvement was maintained. Progression-free survival rates at 5 and 10 years were 95.5% and 84.4%, respectively. P-32-based interstitial brachytherapy can play an effective role in managing patients with cystic craniopharyngiomas. It can be considered a valid alternative to surgery in select patients with a favorable toxicity profile and long-term clinical outcomes.

P-260 Naïve indirect treatment comparison of PanCO, a pilot study of OncoSil P-32 microparticles combined with gemcitabine + nab-paclitaxel or FOLFIRINOX chemotherapy versus standard-of-care treatment in unresectable locally advanced pancreatic cancer

Pancreatic cancer is a malignancy with a very poor prognosis and remains an area of high unmet medical need. Current standard treatment for patients with unresectable locally advanced pancreatic cancer (LAPC) is limited to chemotherapy (CT-only) or chemoradiotherapy following induction CT (ICT+CCRT). International guidelines (e.g. ESMO, ASCO and NCCN) recommend gemcitabine monotherapy as well as other regimens containing gemcitabine or fluoropyrimidines (capecitabine, 5FU) plus other agents, or ICT+CCRT, for the treatment of LAPC. Brachytherapy using beta-emitting phosphorus-32 (P-32) microparticles enables a predetermined radiation dose to be implanted into pancreatic tumours via endoscopic ultrasound (EUS) guidance. The results of a prospective, interventional, open-label, single-arm pilot study of P-32 microparticles (OncoSil TM ; OncoSil Medical) combined with gemcitabine + nab-paclitaxel or FOLFIRINOX chemotherapy demonstrated encouraging safety and efficacy in patients with unresectable LAPC (the PanCO study: NCT03003078). In the absence of a head-to-head randomised controlled trial, a naïve indirect treatment comparison was used to assess the results of the PanCO study against state-of-the-art (SOTA) therapy obtained from a systematic literature review (SLR) of published scientific literature from prospective clinical studies. A SLR was conducted to identify published clinical data on SOTA/‘standard-of-care’ treatments from prospective phase II and III clinical studies in patients with unresectable LAPC treated with CT-only or ICT+CCRT. The SLR outcomes were then compared with the results of the PanCO study in a naïve indirect treatment comparison and analysed using a binomial test. The SLR identified clinical outcomes including overall survival (OS), progression-free survival (PFS), one-year survival, resection rate, disease control rate (DCR) and overall response rate (ORR). In total, there were 46 included studies, comprising 57 arms and 4,327 patients, 2,350 of whom had LAPC. The PanCO study enrolled 50 patients (Intention-to-Treat [ITT] population) of which 42 were implanted with P-32 microparticles (Per Protocol [PP] population), with a median follow-up of 16.1 months. Median OS was significantly longer (p<0.001) in the PanCO study than CT-only and/or ICT+CRT regimens (PanCO PP: 16.0 months; ITT: 15.5 months; vs. SLR combined: 12.7 months; CT-only: 12.7 months; ICT+CCRT: 12.6 months), representing a ∼20% reduction in the risk of death compared to CT-only and ICT+CCRT studies (Hazard Ratio PP: 0.79; ITT: 0.82). One-year survival rates in PanCO were significantly higher than SOTA (p<0.001; PanCO PP: 64.0%; ITT: 63.4%; vs. SLR combined: 52.5%; CT-only: 50.4%; ICT+CCRT: 55.2%). The rate of surgical resection in PanCO was significantly greater than SOTA (p<0.001; PanCO PP: 23.8%; ITT: 20.0%; vs. SLR combined: 9.9%; CT-only: 7.7%; ICT+CCRT: 11.5%). Median PFS was significantly longer (p<0.001) than the SLR combined or CT-only regimens (PanCO PP and ITT: 9.3 months; vs. SLR combined: 7.6 months; CT-only: 6.6 months; ICT+CCRT: 9.1 months). DCR and ORR were also significantly higher than the combined SLR or CT-only regimens (ORR/DCR: PanCO PP 31.0%/100%; ITT: 29.8%/95.7%; vs. SLR combined: 18.2%/80.1%; CT-only: 14.7%/71.3%; ICT+CCRT: 24.2%/88.5%, respectively). The naïve indirect treatment comparison to state-of-the-art therapy indicated that P-32 microparticles combined with standard-of-care chemotherapy may provide significant and clinically relevant benefits for patients with unresectable LAPC and a valuable treatment option in an area of high unmet medical need.

O-1 PanCO: Updated results of an open-label, single-arm pilot study of OncoSil P-32 microparticles in unresectable locally advanced pancreatic adenocarcinoma (LAPC) with gemcitabine + nab-paclitaxel or FOLFIRINOX chemotherapy

Unresectable LAPC has a poor prognosis. Current standard-of-care (SoC) is limited to chemotherapy or chemo-radiotherapy. Phosphorus-32 (P-32) microparticles comprise a brachytherapy device that implants a predetermined dose of beta radiation-emitting P-32 into pancreatic tumors via endoscopic ultrasound (EUS) guidance. Here, we report updated results of the pilot PanCO study of P-32 microparticles combined with SoC chemotherapy in patients with unresectable LAPC.

Intraoperative Phosphorus-32 (P32) High-dose Rate (HDR) Dural Brachytherapy For Primary, Recurrent and Metastatic Intracranial Tumors

Achievement of negative surgical margins for intracranial lesions with dural involvement can be challenging due to proximity of sensitive structures. Radiotherapy (RT) can be used to address residual disease, however prior treatment and adjacent structure tolerance can limit the ability to deliver additional tumoricidal doses. The aim was to describe the safety and utility of phosphorus-32 (P32) plaques used intraoperatively to deliver high doses superficially at the surgical margin.

Long-term outcomes of stereotactic intracavitary brachytherapy for cystic craniopharyngiomas

Objective To assess the long-term outcomes of stereotactic intracystic brachytherapy for the treatment of cystic craniopharyngiomas. Methods A total of 141 consecutive patients with cystic craniopharyngioma treated by stereotactic intracystic phosphorus-32 at Department of Neurosurgery, Navy General Hospital of PLA from January 1996 to December 2015. There were 85 males and 56 females and the mean age was 40.1 years (range: 3-72 years). The calculated cumulative beta dose aimed at the inner surface of the cyst wall was 250 Gy. Results All patients were followed up for 1.0-19.5 years with an average of 9.7±4.5 years. The decreased visual acuity had improved in 68.6% (59/86) of the patients in long-term result. The total tumor response rate was 86.5% (122 cases) including the total response accounting for 44.0% (62 cases), partial response accounting for 36.2% (51 cases) and stable response accounting for 6.3% (9 cases). The rate of no response was 13.5% (19 cases). The recurrence rate was 17% (24 cases). The side effects that occurred during follow-up period included worsening of visual acuity in 13 (9.2%), the third nerve palsy in 2 (1.4%), internal carotid artery occlusion in 1(0.7%), new-onset sexual dysfunction in 5 (3.5%), diabetes insipidus in 7 (5.0%), obesity in 12 (8.5%) and cognitive dysfunction in 10 (7.1%) patients, respectively. The late complication rate was 35.5% (50/141). The mean survival after treatment was 120 months. The actuarial 5-, 10- and 15-yr survival rates were 97.9% (138 cases), 92.9% (131 cases) and 89.3% (126 cases), respectively. Conclusion Stereotactic intracavitary brachytherapy is a valuable treatment alternative for cystic craniopharyngioma, particularly for patients with high surgical risk and recurrent tumors. Key words: Cystic craniopharyngioma; Stereotactic radiosurgery; Phosphorus radioisotopes; Treatment outcome; Long-term

Clinical outcome of radiosynovectomy in haemophilia a patients with chronic knee synovitis

Aim: There are various medical and surgical modalities available at breaking the vicious cycle of synovitis–hemarthrosis-synovitis at an early stage of synovitis in patients of haemophilia. Our study was planned to assess the short term clinical outcome in chronic knee synovitis among haemophilia A patients treated with phosphorus-32 (P-32) radiosynovectomy. Methods: Fifteen haemophilia A patients with chronic knee synovitis were injected with P-32 Samarium radiocolloid into the knees. These patients were clinically assessed at time of injection, at one and at three months post procedure. The parameters evaluated are the Tegner Lysholm Score (TLS), Modified Knee Society Clinical Rating System score (MKSS) and by measuring the circumference of the knee joint pre and post injection. Results: Among the fifteen haemophilia A patients studied, there was statistically significant difference in all three parameters recorded with TLS having χ2 (2) = 27.887 and p value

Efficacy of phosphorus-32 brachytherapy without external-beam radiation for long-term tumor control in patients with craniopharyngioma.

OBJECT Radioactive phosphorus-32 (P32) has been used as brachytherapy for craniopharyngiomas with the hope of providing local control of enlarging tumor cysts. Brachytherapy has commonly been used as an adjunct to the standard treatment of surgery and external-beam radiation (EBR). Historically, multimodal treatment, including EBR, has shown tumor control rates as high as 70% at 10 years after treatment. However, EBR is associated with significant long-term risks, including visual deficits, endocrine dysfunction, and cognitive decline. Theoretically, brachytherapy may provide focused local radiation that controls or shrinks a symptomatic cyst without exposing the patient to the risks of EBR. For this study, the authors reviewed their experiences with craniopharyngioma patients treated with P32 brachytherapy as the primary treatment without EBR. The authors reviewed these patients' records to evaluate whether this strategy effectively controls tumor growth, thus avoiding the need for further surgery or EBR. METHODS The authors performed a retrospective review of pediatric patients treated for craniopharyngioma between 1997 and 2004. This was the time period during which the authors' institution had a relatively high use of P32 for treatment of cystic craniopharyngioma. All patients who had surgery and injection of P32 without EBR were identified. The patient records were analyzed for complications, cyst control, need for further surgery, and need for future EBR. RESULTS Thirty-eight patients were treated for craniopharyngioma during the study period. Nine patients (23.7%) were identified who had surgery (resection or biopsy) with P32 brachytherapy but without initial EBR. These 9 patients represented the study group. For 1 patient (11.1%), there was a complication with the brachytherapy procedure. Five patients (55.5%) required subsequent surgery. Seven patients (77.7%) required subsequent EBR for tumor growth. The mean time between the injection of P32 and subsequent treatment was 1.67 ± 1.50 years (mean ± SD). CONCLUSIONS In this small but focused population, P32 treatment provided limited local control for cyst growth. Brachytherapy alone did not reliably avert the need for subsequent surgery or EBR.

Stereotactic intracavitary brachytherapy with P-32 for cystic craniopharyngiomas in children

Although microsurgery remains the first-line treatment, gross total resection of cystic craniopharyngeomas (CP) is associated with significant morbidity and mortality and the addition of external irradiation to subtotal resection proves to achieve similar tumor control. However, concern regarding long-term morbidity associated with external irradiation in children still remains. With this retrospective analysis, the authors emphasize intracavitary brachytherapy using phosphorus-32 (P-32) as a treatment option for children with cystic CP. Between 1992 and 2009, 17 children (median age 15.4 years; range 7-18 years) with cystic CP underwent intracavitary brachytherapy using P-32. Eleven patients were treated for recurrent tumor cysts; 6 patients were treated primarily. MR imaging revealed solitary cysts in 7 patients; 10 patients had mixed solid-cystic lesions (median tumor volume 11.1ml; range 0.5-78.9ml). The median follow-up time was 61.9 months (range 16.9-196.6 months). Local cyst control could be achieved in 14 patients (82 %). Three patients showed progression of the treated cystic formation (in-field progression) after a median time of 8.3 months (range 5.3-10.3 months), which led to subsequent interventions. The development of new, defined cysts and progression of solid tumor parts (out-of-field progression) occurred in 5 patients and led to additional interventions in 4 cases. There was neither surgery-related permanent morbidity nor mortality in this study. The overall progression-free survival was 75, 63, and 52 % after 1, 3, and 5 years, respectively. Intracavitary brachytherapy using P-32 represents a safe and effective treatment option for children harboring cystic CP, even as primary treatment. However, P-32 does not clearly affect growth of solid tumor parts or the development of new cystic formations.

A clinical study on the treatment of mucocele by bleomyin A5 combined with phosphorus-32 colloid

To evaluate the effect of bleomyin A5 combined with phosphorus-32 colloid in the treatment of mucocele. A total of 214 patients divided into three groups, bleomyin A5 (50 cases), phosphorus-32 colloid (50 cases) and bleomyin A5 combined with phosphorus-32 colloid (114 cases). The efficacy of bleomyin A5 group, phosphorus-32 colloid group, and bleomyin A5 combined with phosphorus-32 colloid group was 84% (42/50), 82% (41/50) and 98% (112/114), respectively. There were significant difference in efficacy among the three groups (P < 0.05). The phosphorus-32 colloid group and the bleomyin A5 group had no significant difference in efficacy (P > 0.05). The independent use of bleomyin A5 and phosphorus-32 colloid is effective, but the combined use of the two methods is more effective.

Estimation of skin dose rate from a catheter bag filled with P-32 solution.

Patients attending for therapy with phosphorus-32 (P-32) may have problems with urinary continence requiring the use of a urinary catheter. P-32 is excreted renally and the contents of the catheter bag will impart a dose to the skin with which the bag is in contact. We simulated a catheter bag filled with P-32-contaminated urine and measured the dose rate per unit activity from the bag. A volume of 25 MBq of P-32 was added to a 500 ml bag of saline and mixed thoroughly. A personal dosimetry badge was fixed to the surface of the bag and left for 48 h before being sent for processing. To account for decay, the cumulative activity in the bag over the 48 h period was calculated and the shallow [Hp(0.07)] dose measured by the badge was divided by the cumulative activity to yield a dose rate per MBq of activity. The measured Hp(0.07) dose was 192.8 mSv, which corresponds to a dose rate per MBq of 169 μSv/h/MBq. This study has shown that the dose rate per MBq from a simulated catheter bag of radioactive phosphorus differs from the dose rates published for other containers. This value may be useful in the risk assessment of P-32 therapy in catheterized patients.

Interstitial radiotherapy using phosphorus-32 for giant posterior fossa cystic craniopharyngiomas.

The treatment for giant posterior fossa cystic craniopharyngiomas remains an important challenge in neurosurgery. The authors evaluated the effects of treating 20 patients with giant posterior fossa cystic craniopharyngiomas using phosphorus-32 (P-32) interstitial radiotherapy at their hospital. The patients included 11 boys and 9 girls with an age range of 3 to 168 months. Before treatment, the tumor volumes ranged from 65 to 215 ml. The intracranial pressure was increased in 16 patients, and optic nerve damage had occurred in 18. The patients received P-32 interstitial radiotherapy following stereotactic cyst-fluid aspiration or drainage and were followed up for 7-138 months. The treatment immediately relieved the intracranial hypertension symptoms in all patients. At the end of follow-up, imaging examinations revealed that the cystic tumors had disappeared, but some residual calcification remained in 12 patients, and had decreased by more than 75% of the initial volume in 8 patients. The damaged optic nerve recovered in 3 cases, improved in 12 cases, remained unchanged in 1 case, and was aggravated in 2 cases. No other severe complications related to surgery or interstitial radiation occurred. During the follow-up period, 7 new cysts appeared in 5 patients who had received additional interstitial radiotherapies with a dose of P-32 that was calculated using the same formula as for the initial treatment. The new tumors then disappeared in 2 patients, significantly shrank in 2 patients, and progressed in 1 patient. For treating giant posterior fossa cystic craniopharyngiomas, P-32 interstitial radiation after stereotactic cyst-fluid aspiration or drainage can achieve a high tumor control rate and has relatively satisfactory clinical effects and quality of life outcomes with few complications.

Phosphorus-32 therapy for cystic craniopharyngiomas

Background and purposeTo examine control rates for predominantly cystic craniopharyngiomas treated with intracavitary phosphorus-32 (P-32). Material and methods22 patients with predominantly cystic craniopharyngiomas were treated at Indiana University between October 1997 and December 2006. Nineteen patients with follow-up of at least 6months were evaluated. The median patient age was 11years, median cyst volume was 9ml, a median dose of 300Gy was prescribed to the cyst wall, and median follow-up was 62months. ResultsOverall cyst control rate after the initial P-32 treatment was 67%. Complete tumor control after P-32 was 42%. Kaplan–Meier 1-, 3-, and 5-year initial freedom-from-progression rates were 68%, 49%, and 31%, respectively. Following salvage therapy, the Kaplan–Meier 1-, 3-, and 5-year ultimate freedom-from-progression rates were 95%, 95%, and 86%, respectively. All patients were alive at the last follow-up. Visual function was stable or improved in 81% when compared prior to P-32 therapy. Pituitary function remained stable in 74% of patients following P-32 therapy. ConclusionsIntracystic P-32 can be an effective and tolerable treatment for controlling cystic components of craniopharyngiomas as a primary treatment or after prior therapies, but frequently allows for progression of solid tumor components. Disease progression in the form of solid tumor progression, re-accumulation of cystic fluid, or development of new cysts may require further radiotherapy or surgical intervention for optimal long-term disease control.

Experimental study of the antitumor effect of phosphorus-32 glass microspheres on the tumor loaded nude mice

Experimental study of the antitumor effect of phosphorus-32 glass microspheres on the tumor loaded nude mice

Experimental induction of osteosarcoma by subperiosteal radioactive phosphorus injections in rats

In search of a predictable experimental model for the study of therapeutic modalities for osteosarcoma, a group of rats had injections of phosphorus-32 (P-32) colloid subperiostally and were followed for the occurrence of malignant bone tumors until death or for 18 months. Of 50 rats, 26 died of unrelated causes and only 24 were included in the study. Two cases of osteosarcomas, one occurring in month 16 and the other at month 18 were induced; one case demonstrated multiple lung metastases. Clear evidence of the sarcoma inducing effect of P-32 has been obtained in this study. However, a high yield experimental osteosarcoma model was not produced.

Effect of aerosol immunization with RE 595 Salmonella minnesota on lung bactericidal activity against Serratia marcescens, Enterobacter cloacae, and Pseudomonas aeruginosa.

Intrapulmonary bactericidal activity was measured after mice were given 3 weekly aerosol exposures to acid-hydrolyzed Re 595 Salmonella minnesota. Ten days after their last immunization, mice were challenged with aerolized Serratia marcescens, Enterobacter cloacae, or Pseudomonas aeruginosa. Quantitative bacterial counts in ground lung were obtained immediately after exposure and again 4 hours later. Enhanced bactericidal activity against Serratia marcescens and Enterobacter cloacae was seen in immunized animals, whereas no difference with Pseudomonas aeruginosa was noted. In separate studies, immunization with Serratia marcescens yielded a similar enhancement of lung bactericidal activity. Mucociliary transport, as measured by disappearance of aerosolized Serratia marcescens labeled with phosphorus-32, was identical for both immunized and control animals. Using a standardized in vitro mouse alveolar macrophage phagocytic system, lung washes from animals immunized with Re 595 Salmonella minnesota had significant opsonic activity for Serratia marcescens but not for Pseudomonas aeruginosa.

Inactivation of staphylococci by alveolar macrophages with preliminary observations on the importance of alveolar lining material.

Separate groups of rats were challenged with aerosolized Staphylococcus aureus or Staphylococcus albus labeled with phosphorus-32, and intrapulmonary bactericidal activity was determined 6 hours later. The rate of inactivation of S. albus was approximately 10 times greater than that seen with S. aureus. Since the alveolar macrophage defense network is the primary site of inactivation of inhaled bacteria in vitro, phagocytic and bactericidal studies were performed to see whether the in vivo differences described could be reproduced in vitro. These studies demonstrated that, whereas rat alveolar macrophages efficiently phagocytosed both types of staphylococci, only S. albus was killed intracellularly. Intracellular bactericidal activity of alveolar macrophages against S. aureus was further studied by lysing extracellular bacteria with lysostaphin after phagocytosis and performing bacterial counts of aliquots of ruptured cell at 0, 2, 4, and 6 hours. Phagocytosis of S. aureus without bactericidal activity wa...

The influence of acute respiratory acidosis on the pulmonary defense mechanisms in rats.

Respiratory acidosis and infection often occur together. Because metabolic abnormalities can enhance susceptibility to respiratory infection, the effect of acute respiratory acidosis on murine resistance to bacterial infection was investigated. After infection with Staphylococcus aureus labeled with phosphorus-32, rats were anesthetized for 4 hours with gas mixtures containing 5, 8, or 10 per cent carbon dioxide with 30 per cent oxygen and 1 per cent halothane in nitrogen. Pulmonary bactericidal activity rates were determined in excised lungs. Bactericidal activity decreased progressively with increasing degrees of respiratory acidosis; arterial blood threshold values were pH 75 mm Hg. Hypoxia was not a factor (arterial oxygen tension > 88 mm Hg), and there was no significant base deficit. Pulmonary edema, as judged histologically and by wet and dry lung weight measurements, was not present. It was concluded that respiratory acidosis impairs pulmonary defense mechanisms...

Regional defense mechanisms of the guinea pig lung.

Many pulmonary diseases, such as tuberculosis, cancer, and pneumonia, are localized to lobes or segments of the lung suggesting regional differences in host defense mechanisms in the lungs. To determine the intrinsic regional differences in transport or phagocytic defense mechanisms, particle deposition, bactericidal activity, and particle transport were measured in each of the 5 individual lobes of guinea pig lungs. Animals were exposed by aerosol to a mixed bacterial suspension containing Proteus mirabilis labeled with sulfur-35 and Staphylococcus aureus labeled with phosphorus-32 or Proteus mirabilis labeled with phosphorus-32 and unlabeled staphylococci. Deposition of particles 3.5 μ or less in diameter was directly proportional to the weight of the lobes; however, on an equal weight basis, no preferential deposition was observed in any of the individual regions. No delay or enhancement in bactericidal activity or transport was observed among the lobes regardless of size or geographic position. These ...

Mutations produced by transmutation of phosphorus-32 to sulfur-32 within Drosophila DNA.

Mutations produced by transmutation of phosphorus-32 to sulfur-32 within Drosophila DNA.