Clinical outcomes of previously untreated patients with unresectable intrahepatic cholangiocarcinoma following proton beam therapy

Abstract Background The effectiveness of proton beam therapy (PBT) as initial treatment for patients with unresectable intrahepatic cholangiocarcinoma (ICC) is unclear, particularly as related to ICC histological subtypes. We performed this study to address this gap in knowledge. Methods Thirty-seven patients with unresectable ICC who underwent PBT as their initial treatment were evaluated. Twenty-seven patients had Child-Pugh class A liver function, 11 exhibited jaundice, and 10 had multiple tumors. Nineteen, 7, and 11 tumors were classified as mass forming (MF), periductal infiltrating (PI), and intraductal growth (IG) types, respectively, based on gross appearance in imaging studies. Patients were classified into the curative group (n = 25) and palliative group (n = 12) depending on whether the planning target volume covered all the macroscopic tumors. Results The 1- and 2-year overall survival rates were 60.3, and 41.4%, respectively; the median survival time (MST) was 15 months for all patients. The MSTs for curative and palliative groups were 25 and 7 months, respectively. Curative treatment and adjuvant chemotherapy significantly improved overall survival, while the presence of periductal infiltrating type tumors was a negative prognostic factor. In the curative group, the 1- and 2-year local control rates were 100 and 71.5%, respectively, while the 1-, and 2-year progression-free survival rates were 58.5, and 37.6%, respectively. No severe acute toxicities were observed. Three patients experienced grade 3 biliary tract infection, although it was unclear whether this was radiotherapy-related. Conclusion PBT may yield to improve survival and local tumor control among patients with unresectable ICC.

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Proton Beam Therapy without Fiducial Markers Using Four-Dimensional CT Planning for Large Hepatocellular Carcinomas

Cancers ◽

10.3390/cancers10030071 ◽

2018 ◽

Vol 10 (3) ◽

pp. 71 ◽

Cited By ~ 2

Author(s):

Satoshi Shibata ◽

Shigeyuki Takamatsu ◽

Kazutaka Yamamoto ◽

Miu Mizuhata ◽

Sayuri Bou ◽

...

Keyword(s):

Proton Beam ◽

Treatment Protocol ◽

Progression Free Survival ◽

Proton Beam Therapy ◽

Target Volume ◽

Tumor Control ◽

Fiducial Markers ◽

Internal Target Volume ◽

4D Ct ◽

Hepatocellular Carcinomas

We evaluated the effectiveness and toxicity of proton beam therapy (PBT) for hepatocellular carcinomas (HCC) >5 cm without fiducial markers using four-dimensional CT (4D-CT) planning. The subjects were 29 patients treated at our hospital between March 2011 and March 2015. The median total dose was 76 Cobalt Gray Equivalents (CGE) in 20 fractions (range; 66–80.5 CGE in 10–32 fractions). Therapy was delivered with end-expiratory phase gating. An internal target volume (ITV) margin was added through the analysis of respiratory movement with 4D-CT. Patient age ranged from 38 to 87 years (median, 71 years). Twenty-four patients were Child–Pugh class A and five patients were class B. Tumor size ranged from 5.0 to 13.9 cm (median, 6.9 cm). The follow-up period ranged from 2 to 72 months (median; 27 months). All patients completed PBT according to the treatment protocol without grade 4 (CTCAE v4.03 (draft v5.0)) or higher adverse effects. The two-year local tumor control (LTC), progression-free survival (PFS), and overall survival (OS) rates were 95%, 22%, and 61%, respectively. The LTC was not inferior to that of previous reports using fiducial markers. Respiratory-gated PBT with 4D-CT planning without fiducial markers is a less invasive and equally effective treatment for large HCCs as PBT with fiducial markers.

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The effectiveness of proton beam therapy for liver metastatic recurrence in gastric cancer patients

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyaa052 ◽

2020 ◽

Vol 50 (8) ◽

pp. 903-908

Author(s):

Hisashi Yamaguchi ◽

Michitaka Honda ◽

Koichi Hamada ◽

Hiroshi Kobayashi ◽

Yukitoshi Todate ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Proton Beam ◽

Local Control ◽

Survival Rates ◽

Progression Free Survival ◽

Proton Beam Therapy ◽

Free Survival ◽

Metastatic Recurrence ◽

Gastric Cancer Patients

Abstract Objective The purpose of this cross-sectional study was to evaluate the efficacy and safety of proton beam therapy for liver metastatic recurrence in gastric cancer patients. Methods Consecutive patients who underwent proton beam therapy from 2010 to 2015 were isolated from our institutional database. Patients with extrahepatic metastatic lesions were excluded. Seven patients were enrolled. The median diameter of target lesions was 31 mm (13–68 mm). The most frequent dosage was 72.6 Gy equivalent in 22 fractions. The effectiveness was assessed based on the local control, overall survival and progression-free survival rates. The local control, overall survival and progression-free survival rates were calculated using the Kaplan–Meier method. Adverse events were described according to the patients’ medical records. Results The median follow-up period was 41.7 months (20.7–66.3 months). The 3-year local control, overall survival and progression-free survival rates were 85.7, 68.6 and 43%, respectively. All patients completed proton beam therapy without interruption. No grade ≥3 adverse events were observed. Conclusions Proton beam therapy might be a treatment option for patients with liver metastasis of gastric cancer.

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Does Risk-Adapted Proton Beam Therapy Have a Role as a Complementary or Alternative Therapeutic Option for Hepatocellular Carcinoma?

Cancers ◽

10.3390/cancers11020230 ◽

2019 ◽

Vol 11 (2) ◽

pp. 230 ◽

Cited By ~ 3

Author(s):

Tae Kim ◽

Joong-Won Park ◽

Bo Kim ◽

Hyunjung Kim ◽

Sung Moon ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Proton Beam ◽

Therapeutic Option ◽

Cancer Control ◽

Proton Beam Therapy ◽

Target Volume ◽

Dose Fractionation ◽

Tumor Control ◽

Grade 3

To evaluate the role of risk-adapted proton beam therapy (PBT) in hepatocellular carcinoma (HCC) patients, a total of 243 HCC patients receiving risk-adapted PBT with three dose-fractionation regimens (regimen A [n = 40], B [n = 60], and C [n = 143]) according to the proximity of their gastrointestinal organs (<1 cm, 1–1.9 cm, and ≥2 cm, respectively) were reviewed: The prescribed doses to planning target volume 1 (PTV1) were 50 gray equivalents (GyE) (EQD2 [equivalent dose in 2 Gy fractions], 62.5 GyE10), 60 GyE (EQD2, 80 GyE10), and 66 GyE (EQD2, 91.3 GyE10) in 10 fractions, respectively, and those of PTV2 were 30 GyE (EQD2, 32.5 GyE10) in 10 fractions. In all patients, the five-year local recurrence-free survival (LRFS) and overall survival (OS) rates were 87.5% and 48.1%, respectively, with grade ≥3 toxicity of 0.4%. In regimens A, B, and C, the five-year LRFS and OS rates were 54.6%, 94.7%, and 92.4% (p < 0.001), and 16.7%, 39.2%, and 67.9% (p < 0.001), respectively. The five-year OS rates of the patients with the Modified Union for International Cancer Control (mUICC) stages I, II, III, and IVA and Barcelona Clinic Liver Cancer (BCLC) stages A, B, and C were 69.2%, 65.4%, 43.8%, and 26.6% (p < 0.001), respectively, and 65.1%, 40%, and 32.2% (p < 0.001), respectively. PBT could achieve promising long-term tumor control and have a potential role as a complementary or alternative therapeutic option across all stages of HCC.

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Does radiosurgery have a role in the management of oligodendrogliomas?

Journal of Neurosurgery ◽

10.3171/2008.5.17582 ◽

2009 ◽

Vol 110 (3) ◽

pp. 564-571 ◽

Cited By ~ 13

Author(s):

Hideyuki Kano ◽

Ajay Niranjan ◽

Aftab Khan ◽

John C. Flickinger ◽

Douglas Kondziolka ◽

...

Keyword(s):

Loss Of Heterozygosity ◽

Small Volume ◽

Survival Rates ◽

Gamma Knife Radiosurgery ◽

Progression Free Survival ◽

Tumor Grade ◽

Target Volume ◽

Tumor Control ◽

Grade Ii ◽

Grade Iii

Object In this study the authors evaluated the role of stereotactic radiosurgery (SRS) in the management of progressive or newly diagnosed small-volume oligodendrogliomas. Tumor control, survival, and complications were assessed in patients with oligodendroglioma who underwent Gamma Knife radiosurgery as a primary or adjuvant procedure. Methods The authors retrospectively reviewed 30 patients with oligodendroglioma (12 Grade II and 18 Grade III) who underwent SRS between 1992 and June 2006 at the University of Pittsburgh. The median patient age was 43.2 years (range 10.8–75.4 years). Twenty-four patients had previously undergone resection of the tumor, whereas tumors in 6 were diagnosed based on biopsy findings. The SRS was performed in 25 patients who had imaging-defined tumor progression despite prior fractionated radiation (22 patients) and/or chemotherapy (20 patients). The median target volume was 15.4 cm3 (range 0.07–48.7 cm3) and the median margin dose was 14.5 Gy (range 11–20 Gy). Results At an average of 39.2 months of follow-up (range 12–133 months), 17 patients were dead and 13 were living. The overall survival rates from diagnosis to 5 and 10 years were 90.9 and 68.2%, respectively, for Grade II and 52.1% at 5 years and 26.1% at 10 years for Grade III. Factors associated with an improved progression-free survival included lower tumor grade and smaller tumor volume. In 13 patients who had loss of heterozygosity testing, patients with 1p19q loss of heterozygosity had a significantly improved survival after diagnosis (p = 0.04). Conclusions The SRS modality is a minimally invasive additional option for patients with residual or recurrent oligodendrogliomas. It may also be considered as an alternative to initial resection in small-volume tumors located in the cortical brain region.

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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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Gamma Knife surgery for convexity, parasagittal, and falcine meningiomas

Journal of Neurosurgery ◽

10.3171/2010.11.jns10112 ◽

2011 ◽

Vol 114 (5) ◽

pp. 1392-1398 ◽

Cited By ~ 29

Author(s):

Toshinori Hasegawa ◽

Yoshihisa Kida ◽

Masayuki Yoshimoto ◽

Hiroshi Iizuka ◽

Dai Ishii ◽

...

Keyword(s):

Gamma Knife ◽

Initial Treatment ◽

Survival Rates ◽

Progression Free Survival ◽

Local Tumor Control ◽

Gamma Knife Surgery ◽

Tumor Control ◽

Tumor Diameter ◽

Primary Tumors ◽

Radiation Induced

Object The aim of this study was to evaluate the outcomes in patients with convexity, parasagittal, or falcine meningiomas treated using Gamma Knife surgery (GKS) and to determine management strategy considering a risk of radiation-induced edema. Methods One hundred twelve patients who harbored 125 convexity, parasagittal, or falcine meningiomas were assessed. Forty-six patients underwent GKS as the initial treatment. The median tumor diameter was 25 mm, and median tumor volume was 8 cm3. The median maximum and margin doses were 30 and 16 Gy, respectively. Results The median follow-up period was 72 months. The actuarial 5- and 10-year progression-free survival rates were 78% and 55%, respectively. The actuarial 5- and 10-year local tumor control rates were 87% and 71%, respectively. Of 29 tumors that developed postradiosurgical edema, 7 were symptomatic. The actuarial symptomatic radiation-induced edema rate was 7%. The incidence of this complication was significantly higher in patients who underwent GKS as the initial treatment. Six of 46 patients for whom GKS was the initial treatment had preradiosurgical edema. Of these 6 patients, 4 developed severe panhemispheric edema after GKS (2 patients with parasagittal tumors, 1 with a falx tumor, and 1 with a convexity tumor). Conclusions Gamma Knife surgery is an effective treatment for convexity, parasagittal, and falcine meningiomas as the initial or adjuvant treatment. However, GKS should be restricted to small- to medium-sized tumors, particularly in patients with primary tumors, because radiation-induced edema is more common in convexity, parasagittal, and falcine meningiomas than skull base meningiomas.

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Photon Versus Proton Beam Therapy for T1–3 Squamous Cell Carcinoma of the Thoracic Esophagus Without Lymph Node Metastasis

Frontiers in Oncology ◽

10.3389/fonc.2021.699172 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yang-Gun Suh ◽

Unurjargal Bayasgalan ◽

Heung Tae Kim ◽

Jong Mog Lee ◽

Moon Soo Kim ◽

...

Keyword(s):

Lymph Node ◽

Clinical Target Volume ◽

Survival Rates ◽

Progression Free Survival ◽

Proton Beam Therapy ◽

Target Volume ◽

Thoracic Esophagus ◽

Free Survival ◽

Extended Field ◽

Photon Radiotherapy

Background and PurposeWe compared treatment outcomes and toxicities of photon radiotherapy versus proton beam therapy (PBT) and evaluated radiation field effects for T1–3 squamous cell carcinoma of the thoracic esophagus (EC) without lymph node metastasis.MethodsMedical records of 77 patients with T1–3N0M0 thoracic EC treated with radiotherapy between 2011 and 2019 were retrospectively analyzed. Among these patients, 61 (79.2%) individuals had T1 EC. The initial clinical target volume encompassed the whole esophagus with or without supraclavicular and/or abdominal lymph nodes (extended-field radiotherapy; 67 patients, 87.0%) or the area 3–5 cm craniocaudally and 1–2 cm radially from the gross tumor volume (involved-field radiotherapy; 10 patients, 13.0%). The final clinical target volume included margins of at least 1 cm from the gross tumor volume, with total radiation doses of 50–66 (median, 66) cobalt gray equivalent. Three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and PBT were used in twenty-four, five, and forty-eight patients, respectively. Concurrent chemotherapy was administered to 17 (22.0%) patients overall and only five (8.0%) T1 patients.ResultsPBT showed significantly lower lung and heart radiation exposure in mean dose, V5, V10, V20, and V30 than photon radiotherapy. The median follow-up for all patients was 46 (interquartile range, 22–72) months. The 5-year progression-free survival and overall survival rates were 56.5 and 64.9%, respectively, with no significant survival difference between photon radiotherapy and PBT. In patients with T1 EC, 5-year progression-free survival and overall survival rates were 62.6 and 73.5%, respectively.ConclusionsExtended-field radiotherapy using modern radiotherapy techniques without chemotherapy showed satisfactory clinical outcomes for lymph node-negative T1 EC.

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Long-Term Clinical Outcomes of Patients Receiving Proton Beam Therapy for Caudate Lobe Hepatocellular Carcinoma

10.21203/rs.3.rs-142699/v1 ◽

2021 ◽

Author(s):

Takashi Iizumi ◽

Toshiyuki Okumura ◽

Yuta Sekino ◽

Hiroaki Takahashi ◽

Yu-Lun Tsai ◽

...

Keyword(s):

Clinical Outcomes ◽

Proton Beam ◽

Survival Rates ◽

Progression Free Survival ◽

Proton Beam Therapy ◽

Caudate Lobe ◽

Feasible Option ◽

Serum Alpha Fetoprotein ◽

Grade 3

Abstract BackgroundHepatocellular carcinoma (HCC) located in the caudate lobe (caudate HCC) is rare; however, patients with this type of tumour have poorer prognoses than do those with HCC in other segments. Despite many published reports on the clinical usefulness of proton beam therapy (PBT) for HCC, data on the clinical outcomes of patients undergoing PBT for caudate HCC remain scare. Therefore, the present study aimed to investigate the outcomes of this group of patients.MethodsThirty patients with caudate HCC who underwent definitive PBT between February 2001 and February 2014 were retrospectively analysed. The total irradiation doses ranged from 55 to 77 (median 72.6) Gy relative biological dose.ResultsThe median follow-up period was 37.5 (range, 3.0–152.0) months. The overall survival rates at 1, 3, and 5 years were 86.6%, 62.8%, and 46.1%, respectively. According to univariate and multivariate analyses, Child-Pugh A (P < 0.01), having a single tumour (P = 0.02), and a low serum alpha-fetoprotein level (P < 0.01) were significant factors predicting longer survival. The local control rates at 1, 3, and 5 years were 100.0%, 85.9%, and 85.9%, respectively, while the corresponding progression-free survival rates were 65.0%, 27.5%, and 22.0%, respectively. No grade 3 or worse adverse events were observed.ConclusionsPBT is effective and safe for the treatment of caudate HCC, and should therefore be considered a feasible option for intervention in patients with this disease.

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High-Dose Proton Beam–Based Radiation Therapy in the Management of Extracranial Chondrosarcomas

International Journal of Particle Therapy ◽

10.14338/ijpt-16-00018.1 ◽

2016 ◽

Vol 3 (3) ◽

pp. 373-381 ◽

Cited By ~ 1

Author(s):

Aashish D. Bhatt ◽

Alex Jacobson ◽

Richard Y. Lee ◽

Christine Giraud ◽

Joseph H. Schwab ◽

...

Keyword(s):

Overall Survival ◽

Proton Beam ◽

Local Control ◽

Multivariate Analyses ◽

Proton Beam Therapy ◽

Local Tumor Control ◽

Tumor Control ◽

High Dose ◽

Local Tumor ◽

Grade Iii

Purpose: Radiation therapy (RT) improves local tumor control in axial chondrosarcomas (CS). It is, however, often difficult to safely deliver the high doses (range, 70.2-77.4 Gy) required for achieving a high likelihood of local control, especially in the spine, using photons. This, however, can be achieved with proton beam therapy (PBT) due to its unique physical characteristics. The main goal of our study is to evaluate the outcomes of CS patients treated with passive scattered PBT. Materials and Methods: Forty-four patients (N = 44) were identified who received PBT as part of their treatment from 1990 to 2012. A retrospective review of their medical and RT treatment records was conducted. Multivariate analyses were performed to identify patient- and tumor-related factors predicting for improved local control and overall survival. Results: Median age was 45.5 years and 55% were female. Median tumor size was 13 cm. Most common anatomical location was the spine (80%). Median follow-up was 29.1 months. Median external beam RT dose was 70.2 Gy relative biological effectiveness (RBE) at 1.8 Gy (RBE) per fraction typically administered using a combination of photon RT + PBT (77%) or PBT alone (23%). Local control was 76% and 57%, and overall survival was 90% and 68% at 2 and 5 years, respectively. Toxicity was acceptable, with the most frequent being wound complications (16%). On multivariate analyses, grade III tumors were significantly associated with decreased local control ( P = 0.019), while female sex ( P = 0.037) and grade III tumors ( P = 0.005) were associated with a poorer overall survival. Conclusions: High-dose proton-based RT in combination with surgery resulted in local tumor control in most of these high-risk CS patients. Female sex was predictive for decreased survival, while higher tumor grade (grade III) was predictive of decreased local control and survival. Proton beam therapy is an attractive treatment modality for these challenging tumors.

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Gamma Knife surgery for intracranial chordoma and chondrosarcoma: radiosurgical perspectives and treatment outcomes

Journal of Neurosurgery ◽

10.3171/2014.7.gks141213 ◽

2014 ◽

Vol 121 (Suppl_2) ◽

pp. 188-197 ◽

Cited By ~ 11

Author(s):

Ji Hee Kim ◽

Hyun Ho Jung ◽

Jong Hee Chang ◽

Jin Woo Chang ◽

Yong Gou Park ◽

...

Keyword(s):

Overall Survival ◽

Gamma Knife ◽

Volume Change ◽

Tumor Volume ◽

Survival Rates ◽

Progression Free Survival ◽

Rank Test ◽

Tumor Control ◽

Free Survival ◽

Log Rank Test

ObjectIntracranial chordomas and chondrosarcomas are histologically low-grade, locally invasive tumors that are reported to be similar in terms of anatomical location, clinical presentation, and radiological findings but different in terms of behavior and outcomes. The purpose of this study was to investigate and compare clinical outcomes after Gamma Knife surgery (GKS) for the treatment of intracranial chordoma and chondrosarcoma.MethodsThe authors conducted a retrospective review of the results of radiosurgical treatment of intracranial chordomas and chondrosarcomas. They enrolled patients who had undergone GKS for intracranial chordoma or chondrosarcoma at the Yonsei Gamma Knife Center, Yonsei University College of Medicine, from October 2000 through June 2007. Analyses included only patients for whom the disease was pathologically diagnosed before GKS and for whom more than 5 years of follow-up data after GKS were available. Rates of progression-free survival and overall survival were analyzed and compared according to tumor pathology. Moreover, the association between tumor control and the margin radiation dose to the tumor was analyzed, and the rate of tumor volume change after GKS was quantified.ResultsA total of 10 patients were enrolled in this study. Of these, 5 patients underwent a total of 8 sessions of GKS for chordoma, and the other 5 patients underwent a total of 7 sessions of GKS for chondrosarcoma. The 2- and 5-year progression-free survival rates for patients in the chordoma group were 70% and 35%, respectively, and rates for patients in the chondrosarcoma group were 100% and 80%, respectively (log-rank test, p = 0.04). The 2- and 5-year overall survival rates after GKS for patients in the chordoma group were 87.5% and 72.9%, respectively, and rates for patients in the chondrosarcoma group were 100% and 100%, respectively (log-rank test, p = 0.03). The mean rates of tumor volume change 2 years after radiosurgery were 79.64% and 39.91% for chordoma and chondrosarcoma, respectively (p = 0.05). No tumor progression was observed when margin doses greater than 16 Gy for chordoma and 14 Gy for chondrosarcoma were prescribed.ConclusionsOutcomes after GKS were more favorable for patients with chondrosarcoma than for those with chordoma. The data also indicated that at 2 years after GKS, the rate of volume change is significantly higher for chordomas than for chondrosarcomas. The authors conclude that radiosurgery with a margin dose of more than 16 Gy for chordomas and more than 14 Gy for chondrosarcomas seems to enhance local tumor control with relatively few complications. Further studies are needed to determine the optimal dose of GKS for patients with intracranial chordoma or chondrosarcoma.

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