scholarly journals Hypofractionated proton beam radiotherapy in patients with unresectable liver tumors: multi-institutional prospective results from the Proton Collaborative Group

2020 ◽  
Author(s):  
Jacob S Parzen ◽  
William Hartsell ◽  
John Chang ◽  
Smith Apisarnthanarax ◽  
Jason Molitoris ◽  
...  

Abstract Background: Recent advances in radiotherapy techniques have allowed ablative doses to be safely delivered to inoperable liver tumors. In this setting, proton beam radiotherapy (PBT) provides the means to escalate radiation dose to the target volume while sparing the uninvolved liver. This study evaluated the safety and efficacy of hypofractionated PBT for liver tumors, predominantly hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).Methods: We evaluated the prospective registry of the Proton Collaborative Group for patients undergoing definitive PBT for liver tumors. Demographic, clinicopathologic, toxicity, and dosimetry information were compiled.Results: To date, 63 patients have been treated at 9 institutions between 2013-2019. Thirty (48%) had HCC and 25 (40%) had ICC. The median dose and biological equivalent dose (BED) delivered was 58.05 GyE (range, 32.5-75) and 80.5 GyE (range, 53.6-100), respectively. The median mean liver BED was 13.9 GyE. Three (4.8%) patients experienced at least one grade ³3 toxicity. With median follow-up of 5.1 months (range, 0.1-40.8), the local control (LC) rate at 1 year was 91.2% for HCC and 90.9% for ICC. The 1-year LC was significantly higher (95.7%) for patients receiving BED greater than 75.2 GyE than for patients receiving BED of 75.2 GyE or lower (84.6%, p = 0.029). The overall survival rate at 1 year was 65.6% for HCC and 81.8% for ICC. Conclusions: Hypofractionated PBT results in excellent LC, sparing of the uninvolved liver, and low toxicity, even in the setting of dose-escalation. Higher dose correlates with improved LC, highlighting the importance of PBT especially in patients with recurrent or bulky disease.

2020 ◽  
Author(s):  
Jacob S Parzen ◽  
William Hartsell ◽  
John Chang ◽  
Smith Apisarnthanarax ◽  
Jason Molitoris ◽  
...  

Abstract Background: Recent advances in radiotherapy techniques have allowed ablative doses to be safely delivered to inoperable liver tumors. In this setting, proton beam radiotherapy (PBT) provides the means to escalate radiation dose to the target volume while sparing the uninvolved liver. This study evaluated the safety and efficacy of hypofractionated PBT for liver tumors, predominantly hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).Methods: We evaluated the prospective registry of the Proton Collaborative Group for patients undergoing definitive PBT for liver tumors. Demographic, clinicopathologic, toxicity, and dosimetry information were compiled.Results: To date, 63 patients have been treated at 9 institutions between 2013-2019. Thirty (48%) had HCC and 25 (40%) had ICC. The median dose and biological equivalent dose (BED) delivered was 58.05 GyE (range, 32.5-75) and 80.5 GyE (range, 53.6-100), respectively. The median mean liver BED was 13.9 GyE. Three (4.8%) patients experienced at least one grade ³3 toxicity. With median follow-up of 5.1 months (range, 0.1-40.8), the local control (LC) rate at 1 year was 91.2% for HCC and 90.9% for ICC. The 1-year LC was significantly higher (95.7%) for patients receiving BED greater than 75.2 GyE than for patients receiving BED of 75.2 GyE or lower (84.6%, p = 0.029). The overall survival rate at 1 year was 65.6% for HCC and 81.8% for ICC. Conclusions: Hypofractionated PBT results in excellent LC, sparing of the uninvolved liver, and low toxicity, even in the setting of dose-escalation. Higher dose correlates with improved LC, highlighting the importance of PBT especially in patients with recurrent or bulky disease.


2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Jacob S. Parzen ◽  
William Hartsell ◽  
John Chang ◽  
Smith Apisarnthanarax ◽  
Jason Molitoris ◽  
...  

Abstract Background Recent advances in radiotherapy techniques have allowed ablative doses to be safely delivered to inoperable liver tumors. In this setting, proton beam radiotherapy (PBT) provides the means to escalate radiation dose to the target volume while sparing the uninvolved liver. This study evaluated the safety and efficacy of hypofractionated PBT for liver tumors, predominantly hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Methods We evaluated the prospective registry of the Proton Collaborative Group for patients undergoing definitive PBT for liver tumors. Demographic, clinicopathologic, toxicity, and dosimetry information were compiled. Results To date, 63 patients have been treated at 9 institutions between 2013 and 2019. Thirty (48%) had HCC and 25 (40%) had ICC. The median dose and biological equivalent dose (BED) delivered was 58.05 GyE (range 32.5–75) and 80.5 GyE (range 53.6–100), respectively. The median mean liver BED was 13.9 GyE. Three (4.8%) patients experienced at least one grade ≥ 3 toxicity. With median follow-up of 5.1 months (range 0.1–40.8), the local control (LC) rate at 1 year was 91.2% for HCC and 90.9% for ICC. The 1-year LC was significantly higher (95.7%) for patients receiving BED greater than 75.2 GyE than for patients receiving BED of 75.2 GyE or lower (84.6%, p = 0.029). The overall survival rate at 1 year was 65.6% for HCC and 81.8% for ICC. Conclusions Hypofractionated PBT results in excellent LC, sparing of the uninvolved liver, and low toxicity, even in the setting of dose-escalation. Higher dose correlates with improved LC, highlighting the importance of PBT especially in patients with recurrent or bulky disease.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 389-389
Author(s):  
Michael David Chuong ◽  
Smith Apisarnthanarax ◽  
William F. Hartsell ◽  
Gary L. Larson ◽  
Henry K. Tsai ◽  
...  

389 Background: The liver is one of the most radiosensitive organs, making radiation therapy (RT) for liver tumors extremely challenging. RT is appropriate only for a minority of liver patients with limited tumor burden; a reduction in the prescribed radiation dose may be needed to lower the probability of radiation-induced liver disease especially in the presence of cirrhosis. Proton beam therapy (PBT) delivers less dose to the liver than photon therapy and is expected to reduce toxicity while also permitting safe dose escalation for some patients with liver tumors. Methods: The Proton Collaborative Group REG001-09 trial (NCT01255748) prospectively collects data for PBT patients with a variety of cancer types. To better understand treatment details and outcomes associated with liver PBT, patients enrolled on the PCG registry trial from 5 institutions who received liver PBT for any cancer between 2012 and 2016 were analyzed. Results: A total of 43 liver cancer patients were included, most with hepatocellular carcinoma (48.8%) or cholangiocarcinoma (25.6%). The vast majority did not have surgery at any time (86%). Most were treatment naive prior to PBT; 2 previously had RT and 8 had prior chemotherapy (mostly cholangiocarcinoma patients). The median total prescribed PBT dose was 58.05 Gy(RBE) (range 21.7-67.5). The median number of prescribed fractions was 15 (range 12-37). PBT was delivered to only the liver in 90.7% of patients; inclusion of lymph nodes was rare. Uniform scanning was used in 26 (72.1%) and pencil beam scanning in 2 patients (4.7%); the delivery technique used for the remaining patients was unknown (23.2%). With median follow up of 4.4 months (range 1.3-17.9), 3 patients (7%) had an intrahepatic recurrence, 2 patients (4.6%) developed distant metastasis, and 10 patients (23.3%) died. No grade 3 or higher toxicity was reported although 17 patients (39.5%) had grade 2 toxicity predominantly fatigue, anorexia, nausea, or vomiting. Conclusions: Although longer follow up is needed to assess late toxicities as well as disease control, early outcomes from the PCG registry trial for liver cancer patients shows that predominantly hypofractionated PBT has a very favorable acute toxicity profile.


2009 ◽  
Vol 27 (32) ◽  
pp. 5350-5355 ◽  
Author(s):  
Odile Oberlin ◽  
Oumaya Fawaz ◽  
Annie Rey ◽  
Patrick Niaudet ◽  
Vita Ridola ◽  
...  

PurposeIfosfamide is widely used in pediatric oncology but its nephrotoxicity may become a significant issue in survivors. This study is aimed at evaluating the incidence of late renal toxicity of ifosfamide and its risk factors.Patients and MethodsOf the 183 patients prospectively investigated for renal function, 77 treated for rhabdomyosarcoma, 39 for other soft tissue sarcoma, 39 for Ewing's sarcoma, and 28 for osteosarcoma were investigated at least 5 years after treatment. No patients had received cisplatin and/or carboplatin. Glomerular and tubular functions were graded according to the Skinner system.ResultsThe median dose of ifosfamide was 54 g/m2(range, 18 to 117 g/m2). After a median follow-up of 10 years, 89.5% of patients had normal tubular function, and 78.5% had normal glomerular function rate (GFR). Serum bicarbonate and calcium were normal in all patients. Hypomagnesemia was observed in 1.2% and hypophosphatemia in 1%. The tubular threshold for phosphate was reduced in 24% of the patients (grade 1 in 15%, grade 2 in 8%, and grade 3 in 0.5%). Glycosuria was detected in 37% of the patients but was more than 0.5 g/24 hours in only 5%. Proteinuria was observed in 12%. Ifosfamide dose and interval from therapy to investigations were predictors of tubulopathy in univariate and multivariate analysis. In a multivariate analysis, an older age at diagnosis and the length of interval since treatment had independent impacts on the risk of abnormal GFR.ConclusionRenal toxicity is moderate with a moderate dose of ifosfamide. However, since it can be permanent and can get worse with time, repeated long-term evaluations are important, and this risk should be balanced against efficacy.


1985 ◽  
Vol 3 (10) ◽  
pp. 1333-1338 ◽  
Author(s):  
S R Smalley ◽  
R G Evans ◽  
R L Richardson ◽  
G M Farrow ◽  
J D Earle

Sixteen consecutive patients with bulky stage II seminoma were treated with primary radiotherapy from 1971 to 1982. Bulky stage II seminoma was defined as either Union Internationale Contre le Cancer (UICC) stage IIC (retroperitoneal metastases greater than 5 cm) or IID (palpable retroperitoneal metastases) with no evidence of visceral or supradiaphragmatic disease. The median age was 38 years (range, 26 to 52) and the median size of retroperitoneal disease was 11.5 cm (range, 5 to 25 cm). Patients were treated with generous radiation ports (such as wide hockey-stick or whole abdomen) often followed by boosts to the sites of bulky disease. Median tumor dose was 3,235 cGy (range, 2,700 to 5,668 cGy). Mediastinal (with or without supraclavicular) prophylactic radiation was administered to 15 of the 16 patients with a median dose of 2,590 cGy (range, 1,200 to 3,700 cGy). Treatment toxicity was mild. All 16 patients achieved a complete remission (CR) with radiotherapy. Median follow-up from the time of diagnosis was 60 months, and all patients are currently disease-free. Two patients recurred after therapy but were rendered disease-free with further radiation. These two relapsing patients have remained disease-free, following initial recurrence, for 8 years. The excellent results obtained with modern imaging and radiotherapeutic techniques justify radiotherapy as the initial treatment of choice for bulky stage II seminomas.


Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1047 ◽  
Author(s):  
Adélaïde Toutée ◽  
Martina Angi ◽  
Sylvain Dureau ◽  
Christine Lévy-Gabriel ◽  
Livia Lumbroso-Le Rouic ◽  
...  

There is increasing evidence of the survival benefit of treating uveal melanoma in an early stage, however it is important to discuss with the patient the associated risk of visual loss. We investigated visual outcomes for uveal melanomas staged T1 (T1UM) treated by proton beam radiotherapy (PBR) as a function of their distance to fovea-optic disc. This retrospective study included a cohort of 424 patients with T1UM treated with PBR between 1991 and 2010 with at least a 5-year follow-up. Visual acuity (VA) was analyzed for patients with posterior edge of tumor located at ≥3 mm (GSup3) or <3 mm (GInf3) from fovea-optic disc. The mean follow-up duration was 122 months, no tumor recurrence was observed. The mean baseline and final VA were 20/25 and 20/32 for GSup3 (n = 75), and 20/40 and 20/80 for GInf3 (n = 317) respectively. The frequency of a 20/200 or greater visual conservation was 93.2%(CI95%:87.7–99.1) and 60.1%(CI95%:54.9–65.9) for GSup3 and GInf3 respectively. This difference between groups was statistically significant (p < 0.001). The risk factors for significant VA loss (less than 20/200) were GInf3 location (p < 0.001), tumor touching optic disc (p = 0.04), initial VA inferior to 20/40 (p < 0.001), documented growth (p = 0.002), and age greater than 60 years (p < 0.001). In summary, PBR for T1UM yields excellent tumor control and good long-term visual outcomes for tumors located ≥3 mm from fovea-optic disc.


2019 ◽  
Vol 30 (6) ◽  
pp. 1397-1402
Author(s):  
Angeliki Psomiadi ◽  
Gertrud Haas ◽  
Michael Edlinger ◽  
Nikolaos E Bechrakis ◽  
Georgios Blatsios

Objective: To evaluate the imaging characteristics of choroidal melanoma before and after proton beam radiotherapy via Optos® ultra-wide-field scanning laser ophthalmoscopy. Methods: Retrospective, descriptive study of choroidal melanoma patients treated with proton beam radiotherapy. All patients underwent full clinical evaluation, including best-corrected visual acuity, ultrasound examination and ultra-wide-field scanning laser ophthalmoscopy imaging in the pseudo-colour (red and green channel) as well as auto-fluorescence mode. Tumours were classified and evaluated according to their location, size, presence of subretinal fluid, drusen, orange pigment and reflectance intensity in ultra-wide-field scanning laser ophthalmoscopy. Tumour sonographic (basal diameter, height) and ultra-wide-field scanning laser ophthalmoscopy imaging dimensions (maximal diameter) were documented. Results: A total of 39 eyes (38 patients) were followed for 24 months (range 6–48 months). Mean best-corrected visual acuity dropped from 20/40 to 20/63 after proton beam radiotherapy. There was no change in the imaging tumour characteristics during follow-up. Subretinal fluid changes were better detected in the autofluorescence compared to pseudo-colour mode. Mean tumour diameter did not significantly change in the ultra-wide-field scanning laser ophthalmoscopy although it did so in the ultrasound. No patient showed local tumour recurrence. Conclusion: The ultra-wide-field scanning laser ophthalmoscopy imaging characteristics of choroidal melanoma in the Optos® system do not significantly change after proton beam radiotherapy after a mean follow-up of 2 years.


Neurosurgery ◽  
2012 ◽  
Vol 72 (3) ◽  
pp. 332-340 ◽  
Author(s):  
Jamie J. Van Gompel ◽  
Matthew L. Carlson ◽  
Bruce E. Pollock ◽  
Eric J. Moore ◽  
Robert L. Foote ◽  
...  

Abstract BACKGROUND: Esthesioneuroblastoma (ENB) is a rare malignant neuroendocrine tumor considered to be radiation sensitive. Local recurrence may be treated in a variety of ways, including stereotactic radiosurgery (SRS); however, little information on its effectiveness is available. OBJECTIVE: To determine whether SRS is effective in providing local control for recurrent ENB. METHODS: This was a retrospective single-institution experience including 109 patients with ENB treated at the Mayo Clinic (1962–2009). Sixty-three patients presented with Kadish stage C disease, and 21 patients developed local recurrence. Of these 21 patients, 7 patients underwent SRS at our institution and an additional patient underwent SRS after transnasal biopsy. Therefore, a total of 8 patients are reported. RESULTS: The median age at time of local recurrence was 50 years. All patients had Kadish C disease at initial diagnosis. Six of 8 patients were found to have Hyams grade 3 disease; the remaining 2 patients had grade 2 disease. The median treatment volume was 8.4 cm3 (mean, 18.9 cm3; range, 1.4-76.3 cm3), and the median dose to the tumor margin was 15 Gy (mean, 14.4 ± 2.2 Gy; range, 10-18 Gy). Of the 16 treatments, 13 had adequate follow-up to assess treatment response, with 92% achieving local control over a median follow-up of 42 months from the time of SRS. Five lesions decreased in size, 7 lesions stabilized, and only 1 lesion had in-field progression. There were no documented complications secondary to SRS. CONCLUSION: SRS appears to be a reasonable and safe option for treatment of intracranial recurrence of ENB.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2770-2770
Author(s):  
Luis Fayad ◽  
Michael Overman ◽  
Barbara Pro ◽  
Peter McLaughlin ◽  
Felipe Samaniego ◽  
...  

Background: Follicular lymphoma grade 3 has a natural history that is more akin to that of diffuse large B-cell lymphoma. The addition of rituximab to standard CHOP has resulted in improved response and survival in diffuse large B-cell lymphoma. Information about outcomes in follicular lymphoma grade 3 is lacking. Methods: A single institution retrospective review of patients with follicular grade 3 lymphoma evaluated at the UTMDACC from 1999 to 2004. Patients were located from the UTMDACC lymphoma database. All patients were initially treated with R-CHOP. Results: Forty-five patients were identified: 51% male, 47% ≥60 years, and 87% follicular grade 3b. The LDH was elevated in 24%, ECOG performance status was >1 in 2%, and >1 site of extranodal involvement was present in 10%. Stage distribution was 11% stage I, 11% stage II, 42% stage III, and 36% stage IV, bulky disease (>7cm) was present in 11%, and B symptoms occurred in 13%. Beta-2 microglobulin was elevated in 57% with values >3 μg/dL in over 50%. IPI distribution was: 46% IPI Low, 38% LI, 11% IH, and 4% IPI High. Overall response rate was 100% with 96% complete responses. Relapse rate by IPI category was 24% for Low IPI, 18% for IPI LI, and 40% for IPI IH, and 100% for the two patients with High IPI. With median follow-up of 33 months, three year failure-free survival (FFS) is 73% (95% CI: 59 to 87%). One patient died (2%) with an overall survival (OS) at three years of 97% (95% CI: 93 to 100%). Conclusion: The addition of rituximab to CHOP provided a high response rate and excellent early survival in this group of mostly good prognosis patients. Relapses were still seen; longer follow-up is needed.


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