Salvage skull base surgery after proton beam therapy for recurrent sinonasal malignancies: A retrospective study.

BACKGROUND: This study aimed to examine treatment outcomes and postoperative complications associated with salvage skull base surgery following radical proton beam therapy (PBT). METHODS: Nine patients who underwent salvage skull base surgery following curative PBT as the initial treatment at our institution between September 2002 and May 2023 were retrospectively reviewed. RESULTS: The cohort comprised four males and five females with a mean age of 48.1 years. The average proton dose administered during initial therapy was 68.5 Gy (relative biological effectiveness). Among the salvage surgeries, eight were anterior skull base surgeries, and one was an anterior middle skull base surgery. No local recurrences or perioperative deaths were observed. Postoperative complications occurred in three patients (33.3%), all experiencing surgical site infections, with one also having cerebrospinal fluid leakage. CONCLUSION: The study demonstrates that salvage skull base surgery after PBT effectively achieves local control and safety in patients with recurrent sinonasal malignancies.

The Japanese nationwide cohort data of proton beam therapy for liver oligometastasis in breast cancer patients.

A nationwide multicenter cohort study on particle therapy was launched by the Japanese Society for Radiation Oncology in Japan in May 2016. We analyzed the outcome of proton beam therapy (PBT) for liver oligometastasis in breast cancers. Cases in which PBT was performed at all Japanese proton therapy facilities between May 2016 and February 2019 were enrolled. The patients were selected based on the following criteria: the primary cancer was controlled, liver recurrence without extrahepatic tumors and no more than three liver lesions. Fourteen females, with a median age of 57 years (range, 44-73) and 22 lesions, were included. The median lesion size, fraction (fr) size and biological effective dose were 44 (20-130) mm, 6.6 (2-8) gray (Gy) (relative biological effectiveness)/fr and 109.6 (52.7-115.2) Gy, respectively. The median follow-up period was 22.8 (4-54) months. The 1-, 2- and 3-year local control (LC) rates of liver metastasis from breast cancer were 100% for all. The 1-, 2- and 3-year overall survival rates were 85.7, 62.5 and 62.5%, respectively. The 1-, 2- and 3-year progression-free survival (PFS) rates were 50.0%, 33.3%, and 16.7%, respectively. The median PFS time was 16 months. Only one patient did not complete PBT due to current disease progression. One patient had Grade 3 radiation-induced dermatitis. None of the patients experienced radiation-induced liver failure during the acute or late phase. Owing to the low incidence of adverse events and the high LC rate, PBT appears to be a feasible option for liver oligometastasis in breast cancers.

Pacemaker Malfunction During Passive Proton Beam Therapy for Localized Prostate Cancer: Case Reports and a Literature Review.

We report two cases of pacemaker malfunction occurring during proton beam therapy (PBT) for localized prostate cancer treatment. The first case involved mode changes in the pacemaker, while the second exhibited prolongation of the RR interval. Remarkably, both cases did not manifest significant clinical changes. Our findings indicate that careful consideration should be given to passive PBT in patients with localized prostate cancer who have pacemakers, like the considerations in patients with thoracic and abdominal cancers. Moreover, our report highlights the importance of recognizing potential cardiac implantable electronic devices malfunction in various PBT scenarios.

Particle beam therapy for pelvic recurrence of colorectal cancer: a registry data analysis in Japan and a systematic review.

The aim of this study was to investigate the efficacy and safety of particle beam therapy (PBT) with proton or carbon ion beam for pelvic recurrence of colorectal cancer (PRCC) by comparing the clinical outcomes of a dataset of prospectively enrolled patients for PBT with those from the literature, which were collected by a systematic review of external X-ray radiotherapy (XRT) and PBT. Patients with PRCC treated at 14 domestic facilities between May 2016 and June 2019 and entered the database for prospective observational follow-up were analyzed. The registry data analyzed included 159 PRCC patients treated with PBT of whom 126 (79%) were treated with carbon ion radiation therapy (CIRT). The 3-year overall survival and local control rate were 81.8 and 76.4%, respectively. Among these PRCC patients, 5.7% had Grade 3 or higher toxicity. Systematic search of PubMed and Cochrane databases published from January 2000 to September 2020 resulted in 409 abstracts for the primary selection. Twelve studies fulfilled the inclusion criteria. With one additional publication, 13 studies were selected for qualitative analysis, including 9 on XRT and 4 on PBT. There were nine XRT studies, which included six on 3D conformal radiotherapy and three on stereotactic body radiation therapy, and four PBT studies included three on CIRT and one on proton therapy. A pilot meta-analysis using literatures with median survival time extractable over a 20-month observation period suggested that PBT, especially CIRT, may be a promising treatment option for PRCC not amenable to curative resection.

Head pleomorphic sarcoma showing murine double minute 2 amplification without a well-differentiated liposarcoma component in a pediatric patient.

BACKGROUND: Murine double minute 2 (MDM2) is an oncogene that inhibits p53, leading to decreased apoptosis. Sarcomas showing MDM2 amplification are rare among pediatric patients. CASE: A 14-year-old boy presented with pleomorphic sarcoma of the head showing MDM2 amplification without a well-differentiated liposarcoma component. Although chemotherapy was initially performed to reduce the tumor size before surgery, the tumor did not shrink. The patient underwent complete surgical resection. Microscopic examination revealed a positive surgical margin; thus, postoperative proton-beam radiotherapy was performed. 3 years after the therapy, no sign of recurrence was observed. CONCLUSION: Macroscopic surgical resection combined with adjuvant postoperative radiotherapy was effective against MDM2-amplified pleomorphic sarcoma refractory to neoadjuvant chemotherapy in a pediatric patient.

Feasibility of linac-based fractionated stereotactic radiotherapy and stereotactic radiosurgery for patients with up to ten brain metastases.

BACKGROUND: Linac-based fractionated stereotactic radiotherapy (fSRT) and stereotactic radiosurgery (SRS) are increasingly being used to manage patients with multiple metastases. This retrospective cohort study aimed to compare the outcomes after linac-based fSRT and SRS between three patient groups classified based on the number of brain metastases (BMs): 1 BM, 2-4 BM, 5-10 BM. METHODS: The data of consecutive patients with 1-10 BMs treated with fSRT or SRS between July 2016 and June 2018 at a single institution were collected. Patients with previous whole-brain radiotherapy (WBRT), concurrent use of WBRT, or surgical resection were excluded from the analysis. A total of 176 patients were classified into three groups according to the number of BMs: 78, 67, and 31 patients in 1 BM, 2-4 BM, and 5-10 BM, respectively. The Kaplan-Meier method was used to estimate overall survival (OS) curves, and the cumulative incidence with competing risks was used to estimate local control (LC), distant intracranial failure (DIF), and radiation necrosis (RN). RESULTS: Median OS was 19.8 months (95% confidence interval [CI] 10.2-27.5), 7.3 months (4.9-11.1), and 5.1 months (4.0-9.0) in 1 BM, 2-4 BM, and 5-10 BM, respectively. Compared to 2-4 BM, 1 BM had significantly better OS (hazard ratio [HR] 0.59, 95% CI 0.40-0.87; p = 0.0075); however, 5-10 BM had comparable OS (HR 1.36, 95% CI 0.85-2.19; p = 0.199). There was no significant difference in LC, DIF, and RN between tumor number groups, but DIF was lower in 1 BM. RN of grade 2 or higher occurred in 21 patients (13.5%); grade 4 and 5 RN were not observed. CONCLUSIONS: The linac-based fSRT and SRS for patients with 5-10 BMs is comparable to that for patients with 2-4 BMs in OS, LC, DIF, and RN. It seems reasonable to use linac-based fSRT and SRS in patients with 5-10 BMs.

Immunological and Genetic Characterization of Patients With Head and Neck Cancer who Developed Recurrence.

BACKGROUND/AIM: The recurrence rate of head and neck squamous cell carcinoma (HNSCC) remains high; thus the control of recurrence is a clinical problem to be challenged. To clarify the precise mechanism, specific immunological biomarkers responsible for recurrence were investigated. PATIENTS AND METHODS: The expression levels of immune response-associated and Shizuoka Cancer Center 820 cancer-associated genes, and genetic mutations from whole-exome sequencing were compared between HNSCC patients who developed recurrence (n=8) and HNSCC patients who did not develop recurrence (n=19) using a volcano plot analysis. Cytokine and epithelial-mesenchymal transition marker genes were analyzed using quantitative PCR. Tumor-infiltrating lymphocytes, immune checkpoint molecules, and human papilloma virus status were investigated using immunohistochemistry (IHC). RESULTS: Twenty-seven evaluable patients with HNSCCs received radiation therapy after surgery. Recurrence was identified in 8 patients. TP53 mutations tended to be higher in patients who developed recurrence than in those who did not develop recurrence (75% vs. 31.6%). Gene expression profiling showed the down-regulation of T cell activation genes (ICOS, CD69 and CD83) and the upregulation of the ERBB4, EGFR, VEGF, HIF1A, TGFB1, TWIST1, IL-8, and PAX7 genes, which suggested the activation of the TP53 mutation-TGF-ß1-PAX7 pathway and epithelial-mesenchymal transition. Additionally, IHC indicated a tendency toward a reduction in T cell accumulation and an increase in M2-type macrophage infiltration in tumors that recurred. CONCLUSION: A TP53 mutation-mediated immune-suppressive state in the tumor microenvironment and TGF-ß1-PAX7-mediated EMT might contribute to the promotion of recurrence in patients with HNSCC after postoperative radiotherapy.

Evaluation of breast cosmetic changes with a computer-software; the breast cancer conservative treatment cosmetic results (BCCT. core) in hypofractionated whole breast irradiation after breast-conserving surgery-supplementary analysis of multicenter single-arm confirmatory trial: JCOG0906.

BACKGROUND: A good cosmetic outcome has been defined as an important endpoint in breast-conserving therapy (BCT). Various evaluation methods have been studied, but the optimal method has yet to be identified. The present supplementary analysis of JCOG0906 focused on comparing evaluation methods for breast cosmetic outcomes following hypofractionated whole breast irradiation (HFWBI) to examine whether a computer-software (the Breast Cancer Conservative Treatment cosmetic results [BCCT. core])-based program evaluation (CE) can be used for Asian women in clinical trials of BCT. METHODS: Of 306 women, 292 underwent institutional evaluation (IE) for breast cosmetic outcomes before (pre) and 3 years after (post) HFWBI using a 4-point scale (excellent/good/fair/poor), and they were evaluated by CE and a central panel evaluation (PE) on the same scale using 292 pairs of pre/post-HFWBI photographs. PE was performed twice by consensus of the same two experts with a 3-year interval. CE was assessed individually by two radiation oncologists, an expert and a non-expert. Intra-observer variability and inter-observer variability were calculated using the kappa (k) and weighted kappa (wk) statistics. RESULTS: The agreement between the first and second PE using pre/post-HFWBI photographs was moderate (k = 0.60, wk = 0.64. k = 0.53, wk = 0.60). The agreement between the expert and non-expert on CE was substantial (k = 0.72, wk = 0.76. k = 0.72, wk = 0.77). The inter-observer variability of CE was smaller than the intra-observer variability of PE. CONCLUSION: CE with BCCT. core was considered a reproducible and an appropriate evaluation method for Asian women in clinical trials of BCT, when breast cosmetic changes were compared between pre/post therapy.

Particle therapy using protons or carbon ions for cancer patients with cardiac implantable electronic devices (CIED): a retrospective multi-institutional study.

PURPOSE: To evaluate the outcomes of particle therapy in cancer patients with cardiac implantable electronic devices (CIEDs). MATERIALS AND METHODS: From April 2001 to March 2013, 19,585 patients were treated with proton beam therapy (PBT) or carbon ion therapy (CIT) at 8 institutions. Of these, 69 patients (0.4%, PBT 46, CIT 22, and PBT + CIT 1) with CIEDs (64 pacemakers, 4 implantable cardioverter defibrillators, and 1 with a cardiac resynchronization therapy defibrillator) were retrospectively reviewed. All the patients with CIEDs in this study were treated with the passive scattering type of particle beam therapy. RESULTS: Six (13%) of the 47 PBT patients, and none of the 23 CIT patients experienced CIED malfunctions (p = 0.105). Electrical resets (7) and over-sensing (3) occurred transiently in 6 patients. The distance between the edge of the irradiation field and the CIED was not associated with the incidence of malfunctions in 20 patients with lung cancer. A larger field size had a higher event rate but the test to evaluate trends as not statistically significant (p = 0.196). CONCLUSION: Differences in the frequency of occurrence of device malfunctions for patients treated with PBT and patients treated with CIT did not reach statistical significance. The present study can be regarded as a benchmark study about the incidence of malfunctioning of CIED in passive scattering particle beam therapy and can be used as a reference for active scanning particle beam therapy.

Multi-Institutional Retrospective Analysis of the Outcomes of Proton Beam Therapy for Patients With 1 to 3 Pulmonary Oligometastases From Various Primary Cancers.

PURPOSE: Our purpose was to evaluate the efficacy of proton beam therapy (PBT) in patients with 1 to 3 pulmonary oligometastases from various primary cancers in Japan. METHODS AND MATERIALS: This multi-institutional retrospective survey included 118 patients with 141 metastatic lung tumors from miscellaneous primary cancers, across 6 Japanese institutions, and involved the analyses of local progression-free rate (LPF), distant progression-free rate, progression-free survival rate, cause-specific survival rate, and overall survival rate (OS). Treatment-induced adverse effects of grade ≥2 were evaluated according to the Common Terminology Criteria for Adverse Events (version 4.0). Cox proportional hazards regression models were used in univariable analysis and multivariable analysis (MVA) for the identification of the prognostic factors of LPF and OS. RESULTS: The median follow-up duration from the time of PBT was 25.5 months. The major primary disease sites included colorectal cancer (42.4%), lung cancer (11.9%), head and neck cancer (8.5%), and kidney cancer (8.5%). For years 1, 2, and 3, LPFs were 92.2%, 86.3%, and 78.4%; distant progression-free rates were 59.1%, 44.1%, and 34.0%; progression-free survival rates were 49.6%, 31.7%, and 24.2%; cause-specific survival rates were 83.4%, 72.5%, and 64.8%; and OS rates were 79.0%, 67.8%, and 59.6%, respectively. Eight patients developed acute adverse effects (grade ≥2). Ten patients developed radiation pneumonitis (grade 2) as a late adverse effect. None of the patients developed severe late toxicity (grade ≥3). Colorectal cancer as the primary disease was the only prognostic factor associated with LPF that remained independently significant in the MVAs performed using 3 sets of parameters (hazard ratio [HR], 3.31-4.76 in 3 MVA sets). In the MVA, the significant prognostic factors for OS were performance status (HR, 2.78; 95% confidence interval, 1.01-7.67) and total tumor volume (HR, 1.01; 95% confidence interval, 1.00-1.02). CONCLUSIONS: PBT provides promising outcomes for pulmonary oligometastasis with acceptable toxicities.

Optimal Androgen Deprivation Therapy Combined with Proton Beam Therapy for Prostate Cancer: Results from a Multi-Institutional Study of the Japanese Radiation Oncology Study Group.

BACKGROUND: Androgen deprivation therapy (ADT) combined with radiation therapy benefits intermediate- and high-risk prostate cancer (PC) patients. The optimal ADT duration in combination with high-dose proton beam therapy (PBT) remains unknown. METHODS: Intermediate- and high-risk PC patients treated with PBT combined with ADT for various durations were analyzed retrospectively. To assess the relationship between ADT and biochemical relapse-free (bRF) rate, Cox proportional hazards models including T stage, prostate specific antigen (PSA) level, Gleason score (GS), and total radiation dose were used. RESULTS: In the intermediate-risk PC patients (n = 520), ADT use improved bRF (HR 0.49, 95% CI 0.26-0.93; p = 0.029), especially in those with multiple intermediate-risk factors (T2b-2c, PSA 10-20 ng/mL, and GS 7). In the high-risk PC patients (n = 555), a longer ADT duration (>6 months) conferred a benefit for bRF (HR 0.54, 95% CI 0.32-0.90; p = 0.018), which was most apparent in patients with multiple high-risk factors (T3a-4, PSA > 20 ng/mL, and GS ≥ 8) treated with ADT for ≥21 months. CONCLUSIONS: Short-term (≤6 months) ADT is beneficial for intermediate-risk PC patients, but likely unnecessary for those with a single risk factor, whereas ADT for >6 months is necessary for high-risk PC patients and ADT for ≥21 months might be optimal for those with multiple risk factors in combination of high-dose PBT.

Radiotherapy for local recurrence of non-small-cell lung cancer after lobectomy and lymph node dissection-can local recurrence be radically cured by radiation?

BACKGROUND: There is no standard therapeutic approach for local recurrence of non-small cell lung cancer (NSCLC) after complete resection. We investigated the outcomes of radiotherapy (RT) for patients with local recurrence. METHODS: We reviewed 46 patients who underwent curative-intent RT for local recurrence after lobectomy or pneumonectomy accompanied with mediastinal lymph node dissection between 2002 and 2014. We analyzed overall survival (OS), progression-free survival (PFS), local control, tumour response and the re-recurrence pattern. RESULTS: Among the 46 patients, 16 received concurrent chemotherapy. The median follow-up period was 48 months. The response rate was 91%. The 5-year OS and local control rates were 47.9 and 65.3%, respectively, and the 5-year PFS rate was 22.8%. Female sex and complete response to radiation were favourable prognostic factors. Of the 33 patients with recurrence after radiation, 32 (97%) had distant metastasis. CONCLUSIONS: Although RT for local recurrence has high efficacy, distant relapse after radiation remains a major issue. Therefore, combination systemic therapy for local recurrence at any site should be further investigated. Since it is difficult to achieve a radical cure for local recurrence using RT, further study, for the administration of post-operative adjuvant therapy, is recommended.

Proton Beam Therapy for Histologically or Clinically Diagnosed Stage I Non-Small Cell Lung Cancer (NSCLC): The First Nationwide Retrospective Study in Japan.

PURPOSE: To investigate the efficacy and safety of proton beam therapy (PBT) for the treatment of stage I non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Six hundred sixty-nine patients with 682 tumors histologically or clinically diagnosed stage I NSCLC according to the seventh edition of Union for International Cancer Control who received passive-scattering PBT from April 2004 and December 2013 in Japan were retrospectively reviewed to analyze survival, local control, and toxicities. RESULTS: Of 669 patients, 486 (72.6%) were men, with a median age of 76 years (range, 42-94 years). NSCLC was histologically confirmed in 440 patients (65.7%). Clinical T stages included T1a (n = 265; 38.9%), T1b (n = 216; 31.7%), and T2a (n = 201; 29.4%). The total irradiation doses of PBT ranged from 74.4 to 131.3 biological effective dose GyE (median, 109.6 biological effective dose GyE). The median follow-up period was 38.2 months (range, 0.6-154.5 months) for all patients. The 3-year overall survival and progression-free survival rates for all patients were 79.5% and 64.1%, respectively. For patients with stage IA tumors, the 3-year overall survival and progression-free survival rates were 82.8% and 70.6%, respectively, and the corresponding rates for patients with stage IB tumors were 70.8% and 47.3%, respectively. The 3-year local progression-free rates for all, stage IA, and stage IB patients were 89.8%, 93.5%, and 79.4%, respectively. The incidence of grade 2, 3, 4, and 5 pneumonitis was 9.8%, 1.0%, 0%, and 0.7%, respectively. The incidence of grade ≥3 dermatitis was 0.4%. No grade 4 or severe adverse events, other than pneumonitis, were observed. CONCLUSIONS: PBT appears to yield acceptable survival rates, with a low rate of toxicities.

A comparison of the outcomes between surgical resection and proton beam therapy for single primary hepatocellular carcinoma.

PURPOSE: There are many treatment choices for hepatocellular carcinoma (HCC), one of which is proton beam therapy (PBT). The purpose of this study was to compare surgical resection (SR) and PBT to clarify the prognostic factors for operable HCC based on a single institution's database. METHODS: Patients with single primary nodular HCC ≤ 100 mm without vessel invasion on pretreatment imaging were divided into the SR group and PBT group. In the PBT group, the patients with unresectable HCC due to their liver function and/or performance status were excluded. RESULTS: There were 314 and 31 patients who underwent SR and PBT, respectively. The median survival time in the SR group was significantly better than in the PBT group (104.1 vs. 64.6 months, p = 0.008). Regarding the relapse-free survival (RFS), there was no significant difference between the SR and PBT groups (33.8 vs. 14.0 months, p = 0.099). CONCLUSION: The RFS was comparable between the PBT and SR groups. However, the PBT group had a significantly worse overall survival than the SR group. SR may therefore be favorable as an initial treatment for HCC compared to PBT.

Particle therapy for prostate cancer: The past, present and future.

Although prostate cancer control using radiotherapy is dose-dependent, dose-volume effects on late toxicities in organs at risk, such as the rectum and bladder, have been observed. Both protons and carbon ions offer advantageous physical properties for radiotherapy, and create favorable dose distributions using fewer portals compared with photon-based radiotherapy. Thus, particle beam therapy using protons and carbon ions theoretically seems suitable for dose escalation and reduced risk of toxicity. However, it is difficult to evaluate the superiority of particle beam radiotherapy over photon beam radiotherapy for prostate cancer, as no clinical trials have directly compared the outcomes between the two types of therapy due to the limited number of facilities using particle beam therapy. The Japanese Society for Radiation Oncology organized a joint effort among research groups to establish standardized treatment policies and indications for particle beam therapy according to disease, and multicenter prospective studies have been planned for several common cancers. Clinical trials of proton beam therapy for intermediate-risk prostate cancer and carbon-ion therapy for high-risk prostate cancer have already begun. As particle beam therapy for prostate cancer is covered by the Japanese national health insurance system as of April 2018, and the number of facilities practicing particle beam therapy has increased recently, the number of prostate cancer patients treated with particle beam therapy in Japan is expected to increase drastically. Here, we review the results from studies of particle beam therapy for prostate cancer and discuss future developments in this field.

Patterns of proton therapy use in pediatric cancer management in 2016: An international survey.

PURPOSE: To facilitate the initiation of observational studies on late effects of proton therapy in pediatric patients, we report on current patterns of proton therapy use worldwide in patients aged less than 22 years. MATERIALS & METHODS: Fifty-four proton centers treating pediatric patients in 2016 in 11 countries were invited to respond to a survey about the number of patients treated during that year by age group, intent of treatment, delivery technique and tumor types. RESULTS: Among the 40 participating centers (participation rate: 74%), a total of 1,860 patients were treated in 2016 (North America: 1205, Europe: 432, Asia: 223). The numbers of patients per center ranged from 1 to 206 (median: 29). Twenty-four percent of the patients were <5 years of age, and 50% <10 years. More than 30 pediatric tumor types were identified, mainly treated with curative intent: 48% were CNS, 25% extra-cranial sarcomas, 7% neuroblastoma, and 5% hematopoietic tumors. About half of the patients were treated with pencil beam scanning. Treatment patterns were broadly similar across the three continents. CONCLUSION: To our knowledge, this survey provides the first worldwide assessment of proton therapy use for pediatric cancer management. Since previous estimates in the United States and Europe, CNS tumors remain the cancer types most commonly treated with protons in 2016. However, the proportion of extra-cranial tumors is growing worldwide. The typically low numbers of patients treated in each center indicate the need for international research collaborations to assess long-term outcomes of proton therapy in pediatric patients.

Preliminary results of proton radiotherapy for pediatric rhabdomyosarcoma: a multi-institutional study in Japan.

To evaluate preliminary results of proton radiotherapy (PRT) for pediatric patients with rhabdomyosarcoma (RMS). From 1987 to 2014, PRT was conducted as initial radiotherapy in 55 patients (35 males, 20 females, median age 5 years, range 0-19) with RMS at four institutes in Japan. Thirty-one, 18, and six patients had embryonal, alveolar, and other RMS, respectively. One, 11, 37, and six patients were in IRSG groups I, II, III, and IV, respectively, and the COG risk group was low, intermediate, and high for nine, 39, and seven patients, respectively. The irradiation dose was 36-60 GyE (median: 50.4 GyE). The median follow-up period was 24.5 months (range: 1.5-320.3). The 1- and 2-year overall survival rates were 91.9% (95% CI: 84.3-99.5%) and 84.8% (95% CI 75.2-94.3%), respectively, and these rates were 100% and 100%, 97.1% and 90.1%, and 57.1% and 42.9% for COG low-, intermediate-, and high-risk groups, respectively. There were 153 adverse events of Grade ≥3, including 141 hematologic toxicities in 48 patients (87%) and 12 radiation-induced toxicities in nine patients (16%). Proton-specific toxicity was not observed. PRT has the same treatment effect as photon radiotherapy with tolerable acute radiation-induced toxicity.

Proton beam therapy in non-small cell lung cancer: state of the art.

This review summarizes the past and present status of proton beam therapy (PBT) for lung cancer. PBT has a unique characteristic called the Bragg peak that enables a reduction in the dose of normal tissue around the tumor, but is sensitive to the uncertainties of density changes. The heterogeneity in electron density for thoracic lesions, such as those in the lung and mediastinum, and tumor movement according to respiration necessitates respiratory management for PBT to be applied in lung cancer patients. There are two types of PBT - a passively scattered approach and a scanning approach. Typically, a passively scattered approach is more robust for respiratory movement and a scanning approach could result in a more conformal dose distribution even when the tumor shape is complex. Large tumors of centrally located lung cancer may be more suitably irradiated than with intensity-modulated radiotherapy (IMRT) or stereotactic body radiotherapy (SBRT). For a locally advanced lung cancer, PBT can spare the lung and heart more than photon IMRT. However, no randomized controlled trial has reported differences between PBT and IMRT or SBRT for early-stage and locally advanced lung cancers. Therefore, a well-designed controlled trial is warranted.