Factors associated with long-term survival in gemcitabine-concurrent proton radiotherapy (GPT) for non-metastatic, locally advanced pancreatic cancer (LAPC) remain unclear. This study aimed to ...determine the factors associated with long-term survival in GPT for non-metastatic LAPC.
The medical records of 123 patients with LAPC treated with GPT between February 2009 and December 2019 at Hyogo Ion Beam Medical Center were retrospectively reviewed to assess the factors associated with long-term survival outcomes.
The median overall survival of the total cohort treated with GPT was 18.7 months. The 1- and 2-year overall, local progression-free, and progression-free survival rates were 70.4% and 35.7%, 78.2% and 59.0%, and 38.6% and 20.8%, respectively. Multivariate analysis revealed that LAPCs at the pancreatic body-tail and those without anterior peripancreatic invasion were independently associated with longer overall survival (P = 0.040 and P = 0.015, respectively). The median overall survival of patients with LAPC at the pancreatic body-tail and those with LAPC without anterior peripancreatic invasion were 24.1 and 28.1 months, respectively. LAPCs at the pancreatic body-tail had a higher volume ratio irradiated over 60 Gy equivalents at gross tumor volume than those at the pancreatic head (P < 0.001). LAPCs with anterior peripancreatic invasion had more peritoneal recurrence within 6 months after GTP than those without anterior peripancreatic invasion (P = 0.039).
GPT is a promising treatment option for patients with LAPC at the pancreatic body-tail and those with LAPC without anterior peripancreatic invasion.
Particle radiotherapy has increasingly gained acceptance for locally advanced pancreatic cancers owing to superior tumor conformity and dosimetry compared to conventional photon radiotherapy. ...However, the close proximity of the pancreas to the stomach and duodenum leads to radiation-induced gastrointestinal toxicities, which hinder the delivery of curative doses to the tumor. To overcome this problem, a surgical spacer was placed between the tumor and gastrointestinal tract, and subsequent proton radiotherapy was performed in this study.
Data from 9 patients who underwent surgical spacer placement and subsequent proton radiotherapy were analyzed. The safety and feasibility of the spacer placement surgery were evaluated; the impact of the spacer on dosimetry was also assessed using dose volume histogram (DVH) analyses, before and after surgical spacer placement.
Surgical spacer placement and subsequent proton radiotherapy were successfully completed in all cases. Surgical spacer placement significantly improved the dose intensity covering 95%, mean, and minimum doses for the gross tumor volume, and the clinical and planning target volume based on the DVH, while respecting the dose constraints of the gastrointestinal tract. Based on the Common Terminology Criteria for Adverse Events, two patients (22.2%) developed gastrointestinal ulcer (Grade 2) at 1 and 35 months, and one patient (11.1%) developed gastric perforation (Grade 4) at 4 months after proton radiotherapy.
Surgical spacer placement in the locally advanced pancreatic body and tail cancers is relatively safe and technically feasible. Comparing radiation plans, surgical spacer placement seems to improve the dose distribution in the locally advanced pancreatic body and tail cancers, which are close to the gastrointestinal tract.
Although many reports have shown the safety and efficacy of stereotactic body radiotherapy (SBRT) for T1N0M0 non–small-cell lung cancer (NSCLC), it is rather difficult to treat T2N0M0 NSCLC, ...especially T2b (>5 cm) tumor, with SBRT. Our hypothesis was that particle therapy might be superior to SBRT in T2 patients. We evaluated the clinical outcome of particle therapy for T2a/bN0M0 NSCLC staged according to the 7th edition of the International Union Against Cancer (UICC) tumor, node, metastasis classification.
From April 2003 to December 2009, 70 histologically confirmed patients were treated with proton (n = 43) or carbon-ion (n = 27) therapy according to institutional protocols. Forty-seven patients had a T2a tumor and 23 had a T2b tumor. The total dose and fraction (fr) number were 60 (Gray equivalent) GyE/10 fr in 20 patients, 52.8 GyE/4 fr in 16, 66 GyE/10 fr in 16, 80 GyE/20 fr in 14, and other in four patients, respectively. Toxicities were scored according to the Common Terminology Criteria for Adverse Events, Version 4.0.
The median follow-up period for living patients was 51 months (range, 24–103). For all 70 patients, the 4-year overall survival, local control, and progression-free survival rates were 58% (T2a, 53%; T2b, 67%), 75% (T2a, 70%; T2b, 84%), and 46% (T2a, 43%; T2b, 52%), respectively, with no significant differences between the two groups. The 4-year regional recurrence rate was 17%. Grade 3 pulmonary toxicity was observed in only two patients.
Particle therapy is well tolerated and effective for T2a/bN0M0 NSCLC. To further improve treatment outcome, adjuvant chemotherapy seems a reasonable option, whenever possible.
Aim
With the increased use of particle therapy for liver cancer, local recurrence after particle therapy increased. Salvage hepatectomy is an acceptable treatment option for local recurrence ...following particle therapy; however, its safety and effectiveness remain unclear. Therefore, this multi‐center study aimed to verify the feasibility and efficacy of salvage hepatectomy and assess clinical issues associated with its application.
Methods
We retrospectively assessed the perioperative outcomes, prognosis, and pathological characteristics of 15 patients who underwent salvage hepatectomy for local recurrence after particle therapy between 2006 and 2019.
Results
Hepatocellular carcinoma and metastatic liver tumors were noted in eight and seven patients, respectively. The mean total dose and number of fractions were 66.5 Gy and 12, respectively, and the mean interval between particle therapy and surgery was 30.1 months. Major hepatectomy was performed in seven cases. Moreover, the mortality rate was 0%, and surgical complications of Clavien‐Dindo grade IIIa or higher were observed in four cases (27%)—two bile leakages, one pleural effusion, and one refractory skin fistula. The median overall survival time and 5‐year overall survival rate after salvage hepatectomy were 29.9 months and 43.1%, respectively. Histological examination of the irradiated liver tissue surrounding the tumor showed sinusoidal dilatation, loss of hepatocyte, and fibrosis in most cases.
Conclusion
Salvage hepatectomy after particle therapy is a feasible therapy; however, the risk of refractory complications associated with particle therapy is relatively high. Therefore, the first‐line treatment for resectable liver cancer should be carefully determined considering second‐line treatment after local recurrence.
This is the first study that verified feasibility and efficacy of salvage hepatectomy for local recurrence after particle therapy and indicated clinical issues and pathological features of this therapy. These data would be a guidepost for surgeons to treat such patients.
Intrahepatic cholangiocarcinoma (ICC) can be treated with chemotherapy in unresectable cases, but outcomes are poor. Proton beam therapy (PBT) may provide an alternative treatment and has good dose ...concentration that may improve local control.
Fifty-nine patients who received initial PBT for ICC from May 2016 to June 2018 at nine centers were included in the study. The treatment protocol was based on the policy of the Japanese Society for Radiation Oncology. Forty patients received 72.6-76 Gy (RBE) in 20-22 fr, 13 received 74.0-76.0 Gy (RBE) in 37-38 fr, and 6 received 60-70.2 Gy (RBE) in 20-30 fr. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier analysis.
The 59 patients (35 men, 24 women; median age: 71 years; range: 41-91 years) had PS of 0 (
= 47), 1 (
= 10), and 2 (
= 2). Nine patients had hepatitis and all 59 cases were considered inoperable. The Child-Pugh class was A (
= 46), B (
= 7), and unknown (
= 6); the median maximum tumor diameter was 5.0 cm (range 2.0-15.2 cm); and the clinical stage was I (
= 12), II (
= 19), III (
= 10), and IV (
= 18). At the last follow-up, 17 patients were alive (median follow-up: 36.7 months; range: 24.1-49.9 months) and 42 had died. The median OS was 21.7 months (95% CI: 14.8-34.4 months). At the last follow-up, 37 cases had recurrence, including 10 with local recurrence. The median PFS was 7.5 months (95% CI: 6.1-11.3 months). In multivariable analyses, Child-Pugh class was significantly associated with OS and PFS, and Child-Pugh class and hepatitis were significantly associated with local recurrence. Four patients (6.8%) had late adverse events of grade 3 or higher.
PBT gives favorable treatment outcomes for unresectable ICC without distant metastasis and may be particularly effective in cases with large tumors.
Abstract Background and purpose This retrospective study aimed to compare the clinical outcomes and late toxicities of proton therapy (PT) with those of carbon ion therapy (CIT) for stage I non-small ...cell lung cancer (NSCLC). Material and methods A total of 111 patients who underwent particle therapy for stage I NSCLC between April 2003 and December 2009 were enrolled in this study. PT ( n = 70) and CIT ( n = 41) were delivered to total doses of 52.8–80 GyE in 4–26 fractions and 52.8–70.2 GyE in 4–26 fractions, respectively. The median follow-up time was 41 months. Results Differences in outcome between the PT and CIT groups regarding 3-year overall survival (72% and 76%, respectively), progression-free survival (44% and 53%, respectively), and local control (81% and 78%, respectively) were not statistically significant. In multivariate analysis, the type of treatment beam did not correlate with overall survival. The severity of late toxicities was comparable between the two groups. Conclusions Clinical results in the PT group were comparable to those in the CIT group. However, this study was a retrospective analysis of a highly heterogeneous population. Consequently, more homogeneous prospective data, large multicentric databases and, ideally, randomized trials are warranted.
To assess the incidence of early delayed or late morbidity of the brain after particle therapy for skull base tumors and head-and-neck cancers.
Between May 2001 and December 2005, 59 patients with ...cancerous invasion of the skull base were treated with proton or carbon ion therapy at the Hyogo Ion Beam Medical Center. Adverse events were assessed according to the magnetic resonance imaging findings (late effects of normal tissue-subjective, objective, management, analytic LENT-SOMA) and symptoms (Common Terminology Criteria for Adverse Events CTCAE, version 3.0). Dose-volume histograms were used to analyze the relationship between the dose and volume of the irradiated brain and the occurrence of brain injury. The median follow-up time was 33 months.
Of the 48 patients treated with proton therapy and 11 patients treated with carbon ion radiotherapy, 8 (17%) and 7 (64%), respectively, developed radiation-induced brain changes (RIBCs) on magnetic resonance imaging (LENT-SOMA Grade 1-3). Four patients (7%) had some clinical symptoms, such as vertigo and headache (CTCAE Grade 2) or epilepsy (CTCAE Grade 3). The actuarial occurrence rate of RIBCs at 2 and 3 years was 20% and 39%, respectively, with a significant difference in the incidence between the proton and carbon ion radiotherapy groups. The dose-volume histogram analyses revealed significant differences between the brain lobes with and without RIBCs in the actuarial volume of brain lobes receiving high doses.
Particle therapies produced minimal symptomatic brain toxicities, but sequential evaluation with magnetic resonance imaging detected a greater incidence of RIBCs. Significant differences were observed in the irradiated brain volume between the brain lobes with and without RIBCs.
Carbon ion therapy is a type of radiotherapy that can deliver high-dose radiation to a tumor while minimizing the dose delivered to organs at risk. Moreover, carbon ions are classified as high linear ...energy transfer radiation and are expected to be effective for even photon-resistant tumors. A 73-year-old man with glottic squamous cell carcinoma, T3N0M0, refused laryngectomy and received carbon ion therapy of 70 Gy (relative biological effectiveness) in 35 fractions. Three months after the therapy, the patient had an upper airway inflammation, and then laryngeal edema and pain occurred. Five months after the therapy, the airway stenosis was severe and computed tomography showed lack of the left arytenoid cartilage and exacerbation of laryngeal necrosis. Despite the treatment, 5 and a half months after the therapy, the laryngeal edema and necrosis had become even worse and the surrounding mucosa was edematous and pale. Six months after the therapy, pharyngolaryngoesophagectomy and reconstruction with free jejunal autograft were performed. The surgical specimen pathologically showed massive necrosis and no residual tumor. Three years after the carbon ion therapy, he is alive without recurrence. The first reported laryngeal squamous cell carcinoma case treated with carbon ion therapy resulted in an unexpected radiation laryngeal necrosis. Tissue damage caused by carbon ion therapy may be difficult to repair even for radioresistant cartilage; therefore, hollow organs reinforced by cartilage, such as the larynx, may be vulnerable to carbon ion therapy. Caution should be exercised when treating tumors in or adjacent to such organs with carbon ion therapy.
•We analyzed the prospective data using Proton-Net database.•Distance between the tumor and gastrointestinal tract is an important predisposing factor.•Proton beam therapy showed good efficacy with a ...low incidence of severe toxicity.
To examine the role of proton beam therapy (PBT) in the treatment of extrahepatic biliary tract cancer (EBC).
We analyzed the data accumulated in the Proton-Net database, which prospectively registered all individual patient data treated with PBT in all Japanese proton institutions from May 2016 to June 2019. The primary endpoint was overall survival (OS), and the secondary endpoints were local control (LC), progression-free survival (PFS), and toxicity.
Ninety-three patients with unresectable and/or recurrent EBC were treated with PBT using a median prescribed dose of 67.5 Gy (RBE) (range, 50–72.6 Gy) in 25 (22–30 fractions). With a median follow-up of 16.3 months, the median survival time was 20.1 months and the 2-year OS was 37.8%. Two-year PFS and LC rates were 20.6% and 66.5%, respectively. Poor liver function (Child-Pugh B, C), a narrower distance between the tumor and digestive tract (2 cm >), and a larger tumor diameter (2 cm <) were identified as poor prognostic factors for OS. PBT-related grade 3 ≤ acute and late adverse events occurred in 5.4% and 4.3% of patients, respectively, including one gastrointestinal late toxicity (duodenal ulcer).
This is the largest prospectively accumulated series of PBT for EBC, and PBT showed favorable outcomes with acceptable toxicity profiles.
Background
The prognosis of patients who have hepatocellular carcinoma (HCC) associated with inferior vena cava tumor thrombus (IVCTT) is very poor, and effective treatment modalities are extremely ...limited. The objective of this study was to determine the therapeutic efficacy of particle radiotherapy for HCC with IVCTT.
Methods
Between June 2001 and January 2009, 16 evaluable patients who had HCC with IVCTT were treated with particle radiotherapy. They were divided into 2 groups: 6 were treated with curative intent; 10 with palliative intent. The local tumor control rates, overall survival rates, and toxicities were evaluated.
Results
All tumors treated with particle radiotherapy remained controlled without local recurrence at the last follow-up. The overall survival rates for the 16 patients at 1 and 3 years were 61.1 and 36.7%, respectively. We observed a significant difference in the survival rates according to treatment policy. The median survival time was 25.4 months for patients treated with curative intent and 7.7 months for those treated with palliative intent. The one-year survival rates were 100.0 and 33.3%, respectively. No Grade 3 or higher treatment-related toxicities were observed.
Conclusions
Particle radiotherapy is thought to be potentially effective and safe for HCC with IVCTT. Considering the current lack of effective and less-invasive local therapy for HCC with IVCTT, particle radiotherapy may therefore be an attractive new therapeutic approach for this type of HCC.
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