Proton Therapy for Major Salivary Gland Cancer: Clinical Outcomes

Abstract Purpose To report clinical outcomes in terms of disease control and toxicity in patients with major salivary gland cancers (SGCs) treated with proton beam therapy. Materials and Methods Clinical and dosimetric characteristics of patients with SGCs treated from August 2011 to February 2020 on an observational, prospective, single-institution protocol were abstracted. Local control and overall survival were calculated by the Kaplan-Meier method. During radiation, weekly assessments of toxicity were obtained, and for patients with ≥ 90 days of follow-up, late toxicity was assessed. Results Seventy-two patients were identified. Median age was 54 years (range, 23-87 years). Sixty-three patients (88%) received postoperative therapy, and nine patients (12%) were treated definitively. Twenty-six patients (36%) received concurrent chemotherapy. Nine patients (12%) had received prior radiation. All (99%) but one patient received unilateral treatment with a median dose of 64 GyRBE (relative biological effectiveness) (interquartile range [IQR], 60-66), and 53 patients (74%) received intensity-modulated proton therapy with either single-field or multifield optimization. The median follow-up time was 30 months. Two-year local control and overall survival rates were 96% (95% confidence interval [CI] 85%-99%) and 89% (95% CI 76%-95%], respectively. Radiation dermatitis was the predominant grade-3 toxicity (seen in 21% [n = 15] of the patients), and grade ≥ 2 mucositis was rare (14%; n = 10 patients). No late-grade ≥ 3 toxicities were reported. Conclusion Proton beam therapy for treatment of major SGCs manifests in low rates of acute mucosal toxicity. In addition, the current data suggest a high rate of local control and minimal late toxicity.

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Results of photon radiotherapy for unresectable salivary gland tumors: is neutron radiotherapy’s local control superior?

Radiology and Oncology ◽

10.2478/raon-2013-0046 ◽

2014 ◽

Vol 48 (1) ◽

pp. 56-61 ◽

Cited By ~ 16

Author(s):

Daniel E. Spratt ◽

Lucas Resende Salgado ◽

Nadeem Riaz ◽

Michael G. Doran ◽

Moses Tam ◽

...

Keyword(s):

Salivary Gland ◽

Local Control ◽

Late Complications ◽

Salivary Gland Tumors ◽

Salivary Gland Cancer ◽

Low Grade ◽

Severe Toxicity ◽

Grade 3 ◽

Photon Radiotherapy

Abstract Background. The results of RTOG-MRC randomized trial of photon (n=15) versus neutron (n=17) therapy in the 1980’s reported an improved local control (LC) with neutron radiotherapy for unresectable salivary gland tumors. Due to increased severe toxicity with neutron radiotherapy and the paucity of neutron-therapy centers, we analyzed our institution’s results of photon radiotherapy for unresectable salivary gland tumors. Patients and methods. From 1990 to 2009, 27 patients with unresectable salivary gland cancer underwent definitive photon radiotherapy at our institution. Nodal involvement on presentation was found in 9 patients. Median dose of radiotherapy was 70 Gy. Chemotherapy was given to 18 patients, most being platinum-based regimens. Local control (LC), locoregional control (LRC), distant metastasis-free survival (DMFS), overall survival (OS), and toxicity outcomes were assessed. Results. With a median follow-up of 52.4 months, the 2/5-year actuarial LC was 69% (95%CI ± 21.0%)/55% (± 24.2%), LRC was 65% (± 21.4%)/47% (± 21.6%), and DMFS was 71% (± 21.8%)/51% (± 22.8%), respectively using competing risk analysis. The median OS was 25.7 months, and the 2/5-year OS rates were 50% (± 19.0%)/29% (± 16.6%), respectively. Higher histologic grade was significant for an increased rate of DM (intermediate grade vs. low grade, p=0.04, HR 7.93; high grade vs. low grade, p=0.01, HR 13.50). Thirteen (48%) patient’s experienced acute grade 3 toxicity. Late grade 3 toxicity occurred in three (11%) patients. Conclusions. Our data compares favorably to neutron radiotherapy with fewer late complications. Photon radiotherapy is an acceptable alternative to neutron radiotherapy in patients who present with unresectable salivary gland tumors.

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A pilot study of proton beam theary for mucosal melanoma of the head and neck

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e17042 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e17042-e17042

Author(s):

S. Zenda ◽

M. Kawashima ◽

R. Kohno ◽

S. Arahira ◽

T. Nishio ◽

...

Keyword(s):

Head And Neck ◽

Proton Beam ◽

Proton Therapy ◽

Progression Free Survival ◽

Late Toxicity ◽

Distant Metastases ◽

Proton Beam Therapy ◽

Mucosal Melanoma ◽

Cervical Lymph Nodes ◽

Number Of Patients

e17042 Background: The aim of this study is to clarify the clinical profile of proton beam therapy for mucosal melanoma of the head and neck. Methods: Patients with mucosal melanoma of the head and neck fulfilling the following criteria were enrolled: histologically confirmed malignant melanoma; N0 and M0 disease. Proton therapy was delivered three times a week with planned total dose of 60 GyE in 15 fractions. Results: From January 2004 through January 2007, thirteen patients were enrolled in this study. Patients’ characteristics were as follows: median age, 75 years (range, 56 to 79); male/female, 7/6; T1/2/3/4/rec, 3/2/0/7/1. All could receive the full dose of proton therapy. The most common acute toxicities were mucositis (grade 3: 15%) and dermatitis (grade 2: 15%). One patient had unilateral impairment of visual acuity possibly related with treatment. Initial local control rate was 77.0% (10/13, 95%CI: 46.2–95.0%). With median follow up period of 33.7 months, median progression free survival was 18.9 months and median survival time was not reached. 2-year overall survival rate was 69.7% (95%CI: 31.6–86.1%). Most frequent site of first failure was cervical lymph nodes outside of PTV. Four patients died of disease; cachexia caused by distant metastases in three and carotid blowout because of nodal disease in one. Conclusions: Proton beam therapy for mucosal melanoma of the head and neck achieved favorable results in this limited number of patients, although further investigation about late toxicity is needed. Now, the phase II study of this treatment is ongoing. No significant financial relationships to disclose.

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Re-irradiation for intra-thoracic tumours and extra-thoracic breast cancer: dose accumulation, evaluation of efficacy and toxicity based on a literature review

British Journal of Radiology ◽

10.1259/bjr.20201292 ◽

2021 ◽

Author(s):

Dorota Gabrys ◽

Roland Kulik ◽

Agnieszka Namysł-Kaletka

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Local Control ◽

Treatment Time ◽

Late Toxicity ◽

Breast Conserving Therapy ◽

Published Data ◽

Overall Treatment Time ◽

Grade 3 ◽

Early Toxicity

The improvement seen in the diagnostic procedures and treatment of thoracic tumours means that patients have an increased chance of longer overall survival. Nevertheless, we can still find those who have had a recurrence or developed a secondary cancer in the previously treated area. These patients require retreatment including re-irradiation. We have reviewed the published data on thoracic re-irradiation which shows that some specific healthy tissues can tolerate a significant dose of irradiation and these patients benefit from aggressive treatment, however, there is a risk of damage to normal tissue under these circumstances. We analysed the literature data on re-irradiation in the areas of vertebral bodies, spinal cord, breast, lung and oesophagus. We evaluated the doses of primary and secondary radiotherapy, the treatment techniques, as well as the local control and median or overall survival in patients treated with re-radiation. The longest OS is reported in the case of re-irradiation after second breast-conserving therapy where the 5 year OS range is 81 to 100% and is shorter in patients with loco-reginal re-irradiation where the 5-y OS range is 18 to 60%. 2 year OS in patients re-irradiated for lung cancer and oesophagus cancer range from 13 to 74% and 18 to 42%, respectively. Majority grade ≥3 toxicity after second breast-conserving therapy was fibrosis up to 35%. For loco-regional breast cancer recurrences, early toxicity occurred in up to 33% of patients resulting in mostly desquamation, while late toxicity was recorded in up to 23% of patients and were mostly ulcerations. Early grade ≥3 lung toxicity developed in up to 39% of patients and up to 20% of Grade five hemoptysis. The most frequently observed early toxicity grade ≥3 in oesophageal cancer was oesophagitis recorded in up to 57% of patients, followed by hematological complications which was recorded in up to 50% of patients. The most common late complications included dysphagia, recorded in up to 16.7% of patients. We have shown that thoracic re-irradiation is feasible and effective in achieving local control in some patients. Re-irradiation should be performed with maximum accuracy and care using the best available treatment methods with a highly conformal, image-guided approach. Due to tremendous technological progress in the field of radiotherapy, we can deliver radiation precisely, shorten the overall treatment time and potentially reduce treatment-related toxicities.

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Outcomes after Radiation Therapy for HIV Positive Patients with Invasive Cervical Cancer

Cancer and Clinical Oncology ◽

10.5539/cco.v7n1p12 ◽

2018 ◽

Vol 7 (1) ◽

pp. 12 ◽

Cited By ~ 1

Author(s):

Victoire Molinier ◽

Florence Huguet ◽

Marcos Ballester ◽

Marina Karmochkine ◽

Christophe Hennequin ◽

...

Keyword(s):

Cervical Cancer ◽

Overall Survival ◽

Radiation Therapy ◽

Local Control ◽

Univariate Analysis ◽

Survival Rates ◽

Late Toxicity ◽

Hiv Positive ◽

Grade 3 ◽

Overall Survival Rates

Objective: To assess tolerance, local control, and survival outcomes for HIV (human immunodeficiency virus) positive patients with locally advanced cervical cancer (CC) treated with external beam radiation therapy (EBRT) and/or brachytherapy from an Assistance Publique - Hôpitaux de Paris (APHP) retrospective cohort.Methods: Between 2000 and 2014, 28 HIV positive patients presenting with a non-metastatic CC were treated in one of the five APHP radiation therapy centers. Fifteen patients (54%) underwent primary surgery. Twenty-four patients (88%) received EBRT, with concurrent chemotherapy in 22 cases, and 68% received brachytherapy.Results: The median follow-up was 58 months. At 5 years, local control (LCR) and overall survival rates (OS) were 56% and 46.5% respectively. A grade 3-4 acute toxicity (mainly hematological toxicity) was reported in 18 patients (64%). In univariate analysis, total irradiation dose (p=0.03) and cisplatin-based chemotherapy (p=0.005) were predictive of acute toxicity. A grade 3-4 late toxicity (mainly gastro-intestinal and renal) was observed in 7 patients (25%). In univariate analysis, HIV stage at diagnosis (p=0.02) and an initial CD4 count <200/mm3 (p=0.03) were predictive factors of late toxicity.Conclusion: In this study including HIV positive patients with CC, local control and overall survival rates seemed to be lower than those reported in the literature for non-HIV patients. We also reported an increase in acute and late toxicity, mainly hematological, underlying the fundamental role of immunosuppression in tolerance to radiation therapy.

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Clinical Effectiveness of Hypofractionated Proton Beam Therapy for Liver Metastasis From Breast Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.783327 ◽

2021 ◽

Vol 11 ◽

Author(s):

Tae Hyun Kim ◽

Keun Seok Lee ◽

Sung Hoon Sim ◽

Yeon-Joo Kim ◽

Dae Yong Kim ◽

...

Keyword(s):

Breast Cancer ◽

Liver Metastasis ◽

Proton Beam ◽

Local Treatment ◽

Progression Free Survival ◽

Clinical Effectiveness ◽

Proton Beam Therapy ◽

Local Progression ◽

Grade 3

BackgroundFew studies of proton beam therapy (PBT) for patients with liver metastasis from breast cancer (LMBC) are available to date. The aim of the present study was to evaluate the clinical effectiveness of PBT for patients with LMBC.Material and MethodsSeventeen patients with LMBC treated with PBT were included in this study. The median prescribed dose of PBT was 66 GyE (range, 60–80) in 10 fractions, 5 times a week. In patients with LMBC receiving PBT, freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) rates were assessed.ResultsThe median follow-up time was 34.2 months (range, 11.5–56.1). The median FFLP time was not yet reached, and the 3-year FFLP rates were 94.1% (95% confidence interval [CI], 82.9–105.3). The median times of PFS and OS were 7.9 months (95% CI, 5.3–10.5) and 39.3 months (95% CI, 33.2–51.9), respectively, and the 3-year PFS and OS rates were 19.6% (95% CI, -1.8–41.0) and 71.7% (95% CI, 46.8–96.6), respectively. Grade 3 or higher adverse events were not observed.ConclusionPBT for patients with LMBC showed promising FFLP and OS with safe toxicity profiles. These findings suggest that PBT can be considered a local treatment option in patients with LMBC.

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A multi-institutional phase II study of high-dose hypofractionated proton beam therapy (HF-PBT) for unresectable primary liver cancers: Long-term outcomes in patients (pts) with hepatocellular carcinoma (HCC).

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.376 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 376-376

Author(s):

Theodore S. Hong ◽

Jennifer Yon-Li Wo ◽

Edgar Ben-Josef ◽

Erin McDonnell ◽

Lorraine C. Drapek ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Proton Beam ◽

Phase Ii ◽

Local Control ◽

Phase Ii Study ◽

Proton Beam Therapy ◽

Post Treatment ◽

Phase Iii ◽

High Dose

376 Background: Retrospective reports of PBT in hepatocellular carcinoma (HCC) demonstrate local control (LC) rates exceeding 85%. We prospectively replicate these findings and explore predictors of overall survival (OS) in pts with unresectable HCC receiving high dose, HF-PBT. Methods: Pts were enrolled on an NCI sponsored, multi-institutional, phase II study (NCT00976898). Key eligibility were unresectable HCC; Child’s A/B; ECOG PS 0-2; no extrahepatic disease; no prior RT. Maximum tumor size was 12 cm if solitary, 10 cm if 2 tumors, and 6 cm if 3. PBT was given in 15 fractions to a maximum total dose of 67.5 GyE. Sample size was calculated to demonstrate > 80% LC at 2 yrs (LC-2). Results: From 2009-2015, 44 patients were treated. Median age was 70 years (53-89) and 37 (84.1%) were male. 35 (79.5%) pts had Child A or no cirrhosis. 32 (72.7%) pts had 1 tumor, 12 (27.2%) had multiple tumors. Median longest tumor dimension was 5.0 cm (range 1.9-12.0). Median baseline AFP was 18.6 ng/mL (range 1.3-66081) and 29 pts (67.4%) had elevated AFP ( > 7.9 ng/mL). Median RT dose delivered was 58.0 GyE (range 40.5-67.5). 1 pt (2%) had grade 3 RT related toxicity (thrombocytopenia). With a median follow up 21.8 mo among 28 survivors, the LC-2 was 94.8% (95% CI 84.5-99.1%). mOS was 49.9 mo (95% CI 17.8 months- upper limit not reached) and mPFS was 13.9 mo (95% CI 8.4-49.9). OS did not differ by CLIP score, PS, prior treatment, vascular thrombus, baseline AFP, size, or dose. Median AFP change from baseline to 3 mo post treatment was a 32.8% reduction. Median time to AFP nadir in pts with elevated baseline levels was 3.9 mo (0-30.5). % decrease in AFP from baseline to 6 mo post-treatment was significantly associated with lower hazard of death. (HR = 0.993, p = 0.016). Conclusions: High dose hypofractionated proton beam therapy demonstrated a high local control rate for HCC with favorable safety profiles, supporting the ongoing evaluation of radiation in HCC in phase III studies. AFP decrease from baseline to 6 months post-radiation is associated with improved overall survival. Clinical trial information: NCT00976898.

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RARE-40. OUTCOMES AFTER PROTON THERAPY FOR SKULL-BASE CHORDOMA: A PROSPECTIVE STUDY

Neuro-Oncology ◽

10.1093/neuonc/noz175.963 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi230-vi230

Author(s):

Adam Holtzman ◽

Ronny Rotondo ◽

Michael Rutenberg ◽

Daniel Indelicato ◽

Dinesh Rao ◽

...

Keyword(s):

Skull Base ◽

Local Control ◽

Proton Therapy ◽

High Dose ◽

Free Survival ◽

3 Dimensional ◽

Grade 3 ◽

Skull Base Chordoma ◽

Cause Specific Survival

Abstract We evaluated treatment outcomes following definitive or adjuvant high-dose, image-guided proton therapy in 91 patients with skull-base chordoma enrolled on a prospective outcomes tracking protocol and treated between February 2007 and February 2018. The median age was 53 years (range, 22–78 years). Patients received passively scattered 3-dimensional conformal proton therapy to a median dose of 73.8 GyRBE (range, 69.6–75.6 GyRBE). Two patients received a component of intensity-modulated radiotherapy. Seventy percent (n=64) were men and 30% (n=27) were woman. Eighty-two percent (n=75) of patients had macroscopic disease at the time of radiotherapy; 18% (n=16) had undergone a macroscopic gross total resection. Overall survival, cause-specific survival, local control, and RT-related grade 3 toxicity-free survival were calculated. Proton therapy-related toxicities were scored using CTCAE v4.0. With a median follow-up of 3.7 years (range, 0.2–10 years), 26 patients experienced disease recurrence, including 26 local, 0 regional, and 1 distant recurrence. The median time to local progression was 2.2 years (range, 0.4–7.0 years). At the time of last follow-up, 66 patients were alive (56 with no evidence of disease progression) and 25 were deceased (18 with disease progression). There were no acute grade 3 toxicities related to the radiation therapy. The 4-year actuarial rates of overall survival, cause-specific survival, local control, and radiation therapy-related grade 3 toxicity-free survival were 83%, 87%, 76% and 83%, respectively. Definitive or adjuvant high-dose passively scattered 3-dimensional conformal proton therapy for skull-base chordoma provides acceptable local control, comparing favorably to historic photon data, with no acute grade ≥3 radiation-related toxicity and an acceptable rate of grade ≥3 late toxicity. Further follow-up of this cohort is necessary to better characterize long-term disease control and late toxicities.

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Minimal acute toxicity from proton beam therapy for major salivary gland cancer

Acta Oncologica ◽

10.1080/0284186x.2019.1698764 ◽

2019 ◽

Vol 59 (2) ◽

pp. 196-200

Author(s):

Michael Chuong ◽

John Bryant ◽

William Hartsell ◽

Gary Larson ◽

Shahed Badiyan ◽

...

Keyword(s):

Salivary Gland ◽

Acute Toxicity ◽

Proton Beam ◽

Proton Beam Therapy ◽

Salivary Gland Cancer ◽

Major Salivary Gland

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A preliminary study of hepatocellular carcinoma post proton beam therapy using MRI as an early prediction of treatment effectiveness

PLoS ONE ◽

10.1371/journal.pone.0249003 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0249003

Author(s):

Shen-Yen Lin ◽

Chien-Ming Chen ◽

Bing-Shen Huang ◽

Ying-Chieh Lai ◽

Kuang-Tse Pan ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Proton Beam ◽

Treatment Effectiveness ◽

Tumor Regression ◽

Regional Lymph Node ◽

Proton Beam Therapy ◽

Tumor Control ◽

Early Prediction

Purpose To demonstrate the feasibility of magnetic resonance imaging (MRI) for early prediction of proton beam therapy (PBT) effectiveness in hepatocellular carcinoma (HCC). Methods Clinical data of the HCC patients without regional lymph node involvement or distant metastasis who received PBT at this institution between 2014 and 2017 were reviewed. A total of 43 patients were included. Tumor regression pattern after PBT were examined on the basis of follow-up duration. The variables were compared between patients with and without early tumor regression (ETR). Results The median follow-up duration was 40 months (range, 9–62 months). The cumulative overall survival rate at 6 months, 1 years and 5 years was 100%, 88.4%, 63.4%, respectively. Child-Pugh class A, local tumor control (LTC), complete response (CR), and ETR were significantly associated with overall survival (p < 0.05 each). Of 43 patients, 25 patients (58.1%) reached CR in the PBT-irradiated region. Twelve patients (27.9%) had a partial response and 3 patients (7.0%) had a stationary disease. Three patients (7.0%) developed in-field progression. The LTC rate at 5 years was 93.0%. Of the 25 patients who achieved a CR in the PBT-irradiated region, the median time to CR was 5 months (range, 1–19 months). Twenty-two patients (51.2%) showed ETR of the HCC, while 21 patients (48.8%) showed non-ETR. A significant association was observed between ETR and CR of the HCC after PBT (p < 0.001). Conclusion The post-PBT MRI follow-up at 3 months is helpful for monitoring therapeutic response. ETR of the HCC predicted a higher rate of CR and was associated with overall survival, which provides more accurate clinical management.

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