Role of mesothelin in carbon nanotube-induced carcinogenic transformation of human bronchial epithelial cells.

Carbon nanotubes (CNTs) have been likened to asbestos in terms of morphology and toxicity. CNT exposure can lead to pulmonary fibrosis and promotion of tumorigenesis. However, the mechanisms underlying CNT-induced carcinogenesis are not well defined. Mesothelin (MSLN) is overexpressed in many human tumors, including mesotheliomas and pancreatic and ovarian carcinomas. In this study, the role of MSLN in the carcinogenic transformation of human bronchial epithelial cells chronically exposed to single-walled CNT (BSW) was investigated. MSLN overexpression was found in human lung tumors, lung cancer cell lines, and BSW cells. The functional role of MSLN in the BSW cells was then investigated by using stably transfected MSLN knockdown (BSW shMSLN) cells. MSLN knockdown resulted in significantly decreased invasion, migration, colonies on soft agar, and tumor sphere formation. In vivo, BSW shMSLN cells formed smaller primary tumors and less metastases. The mechanism by which MSLN contributes to these more aggressive behaviors was investigated by using ingenuity pathway analysis, which predicted that increased MSLN could induce cyclin E expression. We found that BSW shMSLN cells had decreased cyclin E, and their proliferation rate was reverted to nearly that of untransformed cells. Cell cycle analysis showed that the BSW shMSLN cells had an increased G2 population and a decreased S phase population, which is consistent with the decreased rate of proliferation. Together, our results indicate a novel role of MSLN in the malignant transformation of bronchial epithelial cells following CNT exposure, suggesting its utility as a potential biomarker and drug target for CNT-induced malignancies.

Serum Amyloid P-component Level May be a Biomarker for Lung Toxicities and Overall Survival after Thoracic Radiotherapy for Non-small Cell Lung Cancer.

BACKGROUND: Serum amyloid P-component (SAP) contributes to the clearance of apoptotic cells. As one of the main acute-phase reactants, SAP regulates key aspects of inflammation and sets a threshold for immune cell activation. This study aimed to investigate the association of SAP levels with symptomatic lung toxicities after thoracic radiotherapy (TRT) and overall survival (OS) in non-small lung cancer (NSCLC) patients. METHODS: The SAP level at diagnosis and during TRT was evaluated by ELISA in 113 clinically inoperable NSCLC patients. Data of radiation pneumonitis (RP)/lung fibrosis, and OS were recorded. RESULTS: The mean ± SEM values of SAP levels at baseline, week 2, and week 4 during TRT were 83.8 ± 6.4, 36.7 ± 4.8, and 36.5 ± 3.4 µg/mL, respectively (p < 0.0001). Using the median value (83.0 µg/mL) as a cutoff, patients with higher baseline SAP level had longer OS than those with lower SAP level (58.2 vs. 23.1 months, p = 0.044). Baseline SAP level, gender, pathology and BED10 were significantly associated with OS in univariate analysis, while only baseline SAP level, pathology, and BED10 were found to be prognostic for OS in multivariate analysis. Patients with symptomatic RP had lower SAP levels than those with no or mild RP (82.7 ± 7.3 vs. 96.8 ± 4.8 µg/mL, p = 0.024). CONCLUSIONS: The baseline SAP level can be used to predict symptomatic radiation pneumonitis and was prognostic for survival after TRT for NSCLC patients.

Feasibility of image-guided radiotherapy and concurrent chemotherapy for locally advanced nonsmall cell lung cancer.

A retrospective review of 32 patients with stage III nonsmall cell lung cancer who underwent chemoradiation with image-guided radiotherapy (IGRT) was recorded. Acute grade 3-4 hematologic and esophageal toxicities developed in 6 and 13 patients respectively. At a median follow-up of 14.5 months, only one patient developed grade 3 pneumonitis. The median survival was estimated to be 17 months. Five patients (15%) developed loco-regional recurrences, and 17 patients (53%) distant metastases. Grade 3-4 toxicities remained significant during chemoradiation with IGRT. However, the reduced rate of severe pneumonitis despite a high tumor dose is encouraging and needs to be investigated in future prospective studies.

Feasibility of intensity-modulated and image-guided radiotherapy for locally advanced esophageal cancer.

BACKGROUND: In this study the feasibility of intensity-modulated radiotherapy (IMRT) and tomotherapy-based image-guided radiotherapy (IGRT) for locally advanced esophageal cancer was assessed. METHODS: A retrospective study of ten patients with locally advanced esophageal cancer who underwent concurrent chemotherapy with IMRT (1) and IGRT (9) was conducted. The gross tumor volume was treated to a median dose of 70 Gy (62.4-75 Gy). RESULTS: At a median follow-up of 14 months (1-39 months), three patients developed local failures, six patients developed distant metastases, and complications occurred in two patients (1 tracheoesophageal fistula, 1 esophageal stricture requiring repeated dilatations). No patients developed grade 3-4 pneumonitis or cardiac complications. CONCLUSIONS: IMRT and IGRT may be effective for the treatment of locally advanced esophageal cancer with acceptable complications.

Combining stereotactic body radiotherapy with immunotherapy in stage IV non-small cell lung cancer.

Immunotherapy has revolutionized the treatment of metastatic non-small cell lung cancer (NSCLC). Oligometastasis has been associated with better prognosis than widespread metastatic disease and may be curable by stereotactic body radiotherapy (SBRT). SBRT can stimulate immunogenic anti-tumor activity, which can be further augmented when combined with immunotherapy, such as immune checkpoint inhibitors (ICIs). Thus, its combination with immunotherapy was recognized as a promising treatment option, especially in the metastatic setting. However, the most optimal approach to combine SBRT with immunotherapy remains controversial with early clinical evidence emerging. Here, we review the current clinical evidence supporting the combination of SBRT with immunotherapy in the treatment of metastatic NSCLC. Also, we discuss the current controversies and areas for further exploration associated with this treatment strategy.

Mechanistic rationales for combining immunotherapy with radiotherapy.

Immunotherapy consisted mainly of immune checkpoint inhibitors (ICIs) has led to significantly improved antitumor response. However, such response has been observed only in tumors possessing an overall responsive tumor immune micro-environment (TIME), in which the presence of functional tumor-infiltrating lymphocytes (TILs) is critical. Various mechanisms of immune escape from immunosurveillance exist, leading to different TIME phenotypes in correlation with primary or acquired resistance to ICIs. Radiotherapy has been shown to induce antitumor immunity not only in the irradiated primary tumor, but also at unirradiated distant sites of metastases. Such antitumor immunity is mainly elicited by radiation's stimulatory effects on antigenicity and adjuvanticity. Furthermore, it may be significantly augmented when irradiation is combined with immunotherapy, such as ICIs. Therefore, radiotherapy represents one potential therapeutic strategy to restore anti-tumor immunity in tumors presenting with an unresponsive TIME. In this review, the generation of anti-tumor immunity, its impairment, radiation's immunogenic properties, and the antitumor effects of combining radiation with immunotherapy will be comprehensively discussed.

Immunotherapy and Hypofractionated Radiotherapy in Older Patients with Locally Advanced Cutaneous Squamous-Cell Carcinoma of the Head and Neck: A Proposed Paradigm by the International Geriatric Radiotherapy Group.

Cutaneous skin carcinoma is a disease of older patients. The prevalence of cutaneous squamous-cell carcinoma (cSCC) increases with age. The head and neck region is a frequent place of occurrence due to exposure to ultraviolet light. Surgical resection with adjuvant radiotherapy is frequently advocated for locally advanced disease to decrease the risk of loco-regional recurrence. However, older cancer patients may not be candidates for surgery due to frailty and/or increased risk of complications. Radiotherapy is usually advocated for unresectable patients. Compared to basal-cell carcinoma, locally advanced cSCC tends to recur locally and/or can metastasize, especially in patients with high-risk features such as poorly differentiated histology and perineural invasion. Thus, a new algorithm needs to be developed for older patients with locally advanced head and neck cutaneous squamous-cell carcinoma to improve their survival and conserve their quality of life. Recently, immunotherapy with checkpoint inhibitors (CPIs) has attracted much attention due to the high prevalence of program death ligand 1 (PD-L1) in cSCC. A high response rate was observed following CPI administration with acceptable toxicity. Those with residual disease may be treated with hypofractionated radiotherapy to minimize the risk of recurrence, as radiotherapy may enhance the effect of immunotherapy. We propose a protocol combining CPIs and hypofractionated radiotherapy for older patients with locally advanced cutaneous head and neck cancer who are not candidates for surgery. Prospective studies should be performed to verify this hypothesis.

Impact of COVID-19 pandemic on older cancer patients: Proposed solution by the International Geriatric Radiotherapy Group.

Older cancer patients are disproportionally affected by the Coronavirus 19 (COVID-19) pandemic. A higher rate of death among the elderly and the potential for long-term disability have led to fear of contracting the virus in these patients. This fear can, paradoxically, cause delay in diagnosis and treatment that may lead to a poor outcome that could have been prevented. Thus, physicians should devise a policy that both supports the needs of older patients during cancer treatment, and serves to help them overcome their fear so they seek out to cancer diagnosis and treatment early. A combination of telemedicine and a holistic approach, involving prayers for older cancer patients with a high level of spirituality, may improve vaccination rates as well as quality of life during treatment. Collaboration between health care workers, social workers, faith-based leaders, and cancer survivors may be crucial to achieve this goal. Social media may be an important component, providing a means of sending the positive message to older cancer patients that chronological age is not an impediment to treatment.

Feasibility of image-guided radiotherapy based on helical tomotherapy to reduce contralateral parotid dose in head and neck cancer.

BACKGROUND: To evaluate the feasibility of image-guided radiotherapy based on helical Tomotherapy to spare the contralateral parotid gland in head and neck cancer patients with unilateral or no neck node metastases. METHODS: A retrospective review of 52 patients undergoing radiotherapy for head and neck cancers with image guidance based on daily megavoltage CT imaging with helical tomotherapy was performed. RESULTS: Mean contralateral parotid dose and the volume of the contralateral parotid receiving 40 Gy or more were compared between radiotherapy plans with significant constraint (SC) of less than 20 Gy on parotid dose (23 patients) and the conventional constraint (CC) of 26 Gy (29 patients). All patients had PTV coverage of at least 95% to the contralateral elective neck nodes. Mean contralateral parotid dose was, respectively, 14.1 Gy and 24.7 Gy for the SC and CC plans (p < 0.0001). The volume of contralateral parotid receiving 40 Gy or more was respectively 5.3% and 18.2% (p < 0.0001) CONCLUSION: Tomotherapy for head and neck cancer minimized radiotherapy dose to the contralateral parotid gland in patients undergoing elective node irradiation without sacrificing target coverage.

Effectiveness of prophylactic retropharyngeal lymph node irradiation in patients with locally advanced head and neck cancer.

BACKGROUND: The aim of the study is to assess the effectiveness of intensity-modulated radiotherapy (IMRT) or image-guided radiotherapy (IGRT) for the prevention of retropharyngeal nodal recurrences in locally advanced head and neck cancer. METHODS: A retrospective review of 76 patients with head and neck cancer undergoing concurrent chemoradiation or postoperative radiotherapy with IMRT or IGRT who were at risk for retropharyngeal nodal recurrences because of anatomic site (hypopharynx, nasopharynx, oropharynx) and/or the presence of nodal metastases was undertaken.The prevalence of retropharyngeal nodal recurrences was assessed on follow-up positron emission tomography (PET)-CT scans. RESULTS: At a median follow-up of 22 months (4-53 months), no patient developed retropharyngeal nodal recurrences. CONCLUSION: Prophylactic irradiation of retropharyngeal lymph nodes with IMRT or IGRT provides effective regional control for individuals at risk for recurrence in these nodes.

Rationale for Combing Stereotactic Body Radiation Therapy with Immune Checkpoint Inhibitors in Medically Inoperable Early-Stage Non-Small Cell Lung Cancer.

Stereotactic body radiation therapy (SBRT) has been widely adopted as an alternative to lobar resection in medically inoperable patients with lymph-node negative (N0) early-stage (ES) non-small cell lung cancer (NSCLC). Excellent in-field local control has been consistently achieved with SBRT in ES NSCLC ≤ 3 cm in size. However, the out-of-field control following SBRT remains suboptimal. The rate of recurrence, especially distant recurrence remains high for larger tumors. Additional systemic therapy is warranted in N0 ES NSCLC that is larger in size. Radiation has been shown to have immunomodulatory effects on cancer, which is most prominent with higher fractional doses. Strong synergistic effects are observed when immune checkpoint inhibitors (ICIs) are combined with radiation doses in SBRT's dose range. Unlike chemotherapy, ICIs can potentiate a strong systemic response outside of the irradiated field when combined with SBRT. Together with their less toxic nature, ICIs represent a very suitable class of systemic agents to be combined with SBRT when treating ES NSCLC with high-risk features, such as larger tumor size. In this review, we describe the rationale and emerging evidence, as well as ongoing investigations in this area.

Stereotactic Body Radiotherapy and Immunotherapy for Older Patients with Oligometastases: A Proposed Paradigm by the International Geriatric Radiotherapy Group.

The standard of care for metastatic disease is systemic therapy. A unique subset of patients with limited metastatic disease defined as distant involvement of five anatomic sites or less (oligometastases) have a better chance of remission or improved survival and may benefit from local treatments such as surgery or stereotactic body radiotherapy (SBRT). However, to prevent further spread of disease, systemic treatment such as chemotherapy, targeted therapy, and hormonal therapy may be required. Older patients (70 years old or above) or physiologically frail younger patients with multiple co-morbidities may not be able to tolerate the conventional chemotherapy due to its toxicity. In addition, those with a good performance status may not receive optimal chemotherapy due to concern about toxicity. Recently, immunotherapy with checkpoint inhibitors (CPI) has become a promising approach only in the management of program death ligand 1 (PD-L1)-positive tumors. Thus, a treatment method that elicits induction of PD-L1 production by tumor cells may allow all patients with oligometastases to benefit from immunotherapy. In vitro studies have demonstrated that high dose of radiotherapy may induce formation of PD-L1 in various tumors as a defense mechanism against inflammatory T cells. Clinical studies also corroborated those observations. Thus, SBRT, with its high precision to minimize damage to normal organs, may be a potential treatment of choice for older patients with oligometastases due to its synergy with immunotherapy. We propose a protocol combining SBRT to achieve a minimum radiobiologic equivalent dose around 59.5 Gy to all tumor sites if feasible, followed four to six weeks later by CPI for those cancer patients with oligometastases. All patients will be screened with frailty screening questionnaires to identify individuals at high risk for toxicity. The patients will be managed with an interdisciplinary team which includes oncologists, geriatricians, nurses, nutritionists, patient navigators, and social workers to manage all aspects of geriatric patient care. The use of telemedicine by the team may facilitate patient monitoring during treatment and follow-up. Preliminary data on toxicity, local control, survival, and progression-free survival may be obtained and serve as a template for future prospective studies.

Is immunotherapy at reduced dose and radiotherapy for older patients with locally advanced non-small lung cancer feasible?-a narrative review by the international geriatric radiotherapy group.

Background and Objective: The standard of care for locally advanced non-small cell lung cancer (NSCLC) is either surgery followed by adjuvant chemotherapy with or without radiotherapy or concurrent chemotherapy and radiotherapy. However, older patients (70 years old or above) with multiple co-morbidities may not be able to tolerate the combined treatment due to its toxicity. Since lung cancer prevalence increases significantly with age, a new algorithm needs to be investigated to allow curative treatment for those with locally advanced disease. Methods: A literature search of the literature was conducted through PubMed and Google Scholar using search terms such as locally advanced NSCLC, older cancer patients, immunotherapy with check point inhibitors (CPI), and image-guided radiotherapy (IGRT). Abstracts were screened, full articles fitting the article topic were reviewed, and duplicated and non-English articles were excluded. Key Content and Findings: Recently, CPI has been introduced and proven effective for selected patients with increased program death ligand 1 (PD-L1) expression (50% or above). A reduced dose for CPI (RDCPI) may be as effective as a full dose and may decrease treatment cost. New radiation technique such as IGRT may also minimize radiotherapy complication through normal lung and cardiac sparing. Conclusions: IGRT and RDCPI may be an innovative option for older patients with locally advanced NSCLC and high PD-L1 expression and needs to be investigated in future prospective studies.

Immunotherapy and Modern Radiotherapy Technique for Older Patients with Locally Advanced Head and Neck Cancer: A Proposed Paradigm by the International Geriatric Radiotherapy Group.

The standard of care for locally advanced head and neck cancer is concurrent chemoradiation or postoperative irradiation with or without chemotherapy. Surgery may not be an option for older patients (70 years old or above) due to multiple co-morbidities and frailty. Additionally, the standard chemotherapy of cisplatin may not be ideal for those patients due to oto- and nephrotoxicity. Though carboplatin is a reasonable alternative for cisplatin in patients with a pre-existing hearing deficit or renal dysfunction, its efficacy may be inferior to cisplatin for head and neck cancer. In addition, concurrent chemoradiation is frequently associated with grade 3-4 mucositis and hematologic toxicity leading to poor tolerance among older cancer patients. Thus, a new algorithm needs to be developed to provide optimal local control while minimizing toxicity for this vulnerable group of patients. Recently, immunotherapy with check point inhibitors (CPI) has attracted much attention due to the high prevalence of program death-ligand 1 (PD-L1) in head and neck cancer. In patients with recurrent or metastatic head and neck cancer refractory to cisplatin-based chemotherapy, CPI has proven to be superior to conventional chemotherapy for salvage. Those with a high PD-L1 expression defined as 50% or above or a high tumor proportion score (TPS) may have an excellent response to CPI. This selected group of patients may be candidates for CPI combined with modern radiotherapy techniques, such as intensity-modulated image-guided radiotherapy (IM-IGRT), volumetric arc therapy (VMAT) or proton therapy if available, which allow for the sparing of critical structures, such as the salivary glands, oral cavity, cochlea, larynx and pharyngeal muscles, to improve the patients' quality of life. In addition, normal organs that are frequently sensitive to immunotherapy, such as the thyroid and lungs, are spared with modern radiotherapy techniques. In fit or carefully selected frail patients, a hypofractionated schedule may be considered to reduce the need for daily transportation. We propose a protocol combining CPI and modern radiotherapy techniques for older patients with locally advanced head and neck cancer who are not eligible for cisplatin-based chemotherapy and have a high TPS. Prospective studies should be performed to verify this hypothesis.

Effectiveness of image-guided radiotherapy for locally advanced rectal cancer.

BACKGROUND: Image-guided radiotherapy (IGRT) combines precise target visualization with optimal delivery of radiation dose to spare normal tissue from radiation and may potentially reduce side-effects and long-term treatment complications. We have assessed the effectiveness of IGRT for locally advanced rectal cancer. METHODS: A retrospective review of 22 patients with locally advanced rectal cancer who underwent preoperative chemoradiation was conducted. RESULTS: Nineteen patients (median age, 69 years) underwent surgical resection after chemoradiation. All 19 patients achieved complete resection with negative margins. Seven patients (32%) had no residual tumor in the surgical specimen. One patient had grade 4 gastrointestinal toxicity and hematological toxicity probably related to inadvertent overdosing of capecitabine. The median survival for the whole group-patients who had pCR and those who did not have pCR-was 14, 17, and 15 months, respectively. CONCLUSIONS: Image-guided radiotherapy provided effective treatment for locally advanced rectal cancer with minimal toxicity and should be investigated in future prospective trials.

Classification of Non-Small Cell Lung Cancer's Tumor Immune Micro-Environment and Strategies to Augment Its Response to Immune Checkpoint Blockade.

Immune checkpoint blockade (ICB) with checkpoint inhibitors has led to significant and durable response in a subset of patients with advanced stage EGFR and ALK wild-type non-small cell lung cancer (NSCLC). This has been consistently shown to be correlated with the unique characteristics of each patient's tumor immune micro-environment (TIME), including the composition and distribution of the tumor immune cell infiltrate; the expression of various checkpoints by tumor and immune cells, such as PD-L1; and the presence of various cytokines and chemokines. In this review, the classification of various types of TIME that are present in NSCLC and their correlation with response to ICB in NSCLC are discussed. This is conducted with a focus on the characteristics and identifiable biomarkers of different TIME subtypes that may also be used to predict NSCLC's clinical response to ICB. Finally, treatment strategies to augment response to ICB in NSCLC with unresponsive types of TIME are explored.

Establishment and characterization of a model of acquired resistance to epidermal growth factor receptor targeting agents in human cancer cells.

PURPOSE: The epidermal growth factor receptor (EGFR) is recognized as a key mediator of proliferation and progression in many human tumors. A series of EGFR-specific inhibitors have recently gained Food and Drug Administration approval in oncology. These strategies of EGFR inhibition have shown major tumor regressions in approximately 10% to 20% of advanced cancer patients. Many tumors, however, eventually manifest resistance to treatment. Efforts to better understand the underlying mechanisms of acquired resistance to EGFR inhibitors, and potential strategies to overcome resistance, are greatly needed. EXPERIMENTAL DESIGN: To develop cell lines with acquired resistance to EGFR inhibitors we utilized the human head and neck squamous cell carcinoma tumor cell line SCC-1. Cells were treated with increasing concentrations of cetuximab, gefitinib, or erlotinib, and characterized for the molecular changes in the EGFR inhibitor-resistant lines relative to the EGFR inhibitor-sensitive lines. RESULTS: EGFR inhibitor-resistant lines were able to maintain their resistant phenotype in both drug-free medium and in athymic nude mouse xenografts. In addition, EGFR inhibitor-resistant lines showed a markedly increased proliferation rate. EGFR inhibitor-resistant lines had elevated levels of phosphorylated EGFR, mitogen-activated protein kinase, AKT, and signal transducer and activator of transcription 3, which were associated with reduced apoptotic capacity. Subsequent in vivo experiments indicated enhanced angiogenic potential in EGFR inhibitor-resistant lines. Finally, EGFR inhibitor-resistant lines showed cross-resistance to ionizing radiation. CONCLUSIONS: We have developed EGFR inhibitor-resistant human head and neck squamous cell carcinoma cell lines. This model provides a valuable preclinical tool to investigate molecular mechanisms of acquired resistance to EGFR blockade.

Comparison of Long-term Survival of Patients With Early-Stage Non-Small Cell Lung Cancer After Surgery vs Stereotactic Body Radiotherapy.

Importance: Previous comparisons of surgery and stereotactic body radiotherapy (SBRT) for early-stage (ES) non-small cell lung cancer (NSCLC) did not account for the extent of regional lymph node examination (LNE) during surgery. Objective: To compare long-term overall survival (OS) of patients with ES NSCLC after surgery vs SBRT when the extent of regional LNE in patients undergoing surgery is thoroughly considered. Design, Setting, and Participants: Cohort study with survival comparisons using the multivariable Cox proportional hazards model and after propensity score matching. Data from the National Cancer Database were analyzed from October 28, 2018, through April 18, 2019. Patients with ES NSCLC diagnosed between January 1, 2004, and December 31, 2015, who underwent any curative-intent surgery or SBRT were included. Main Outcomes and Measures: Long-term OS. Results: Of 104 709 total patients, 91 330 underwent surgery (42 508 [46.5%] male; median [interquartile range] age, 68 [61-75] years) and 13 379 received SBRT (6065 [45.3%] male; median [interquartile range] age, 75 [68-81] years). Surgery, especially lobectomy (hazard ratio [HR], 0.53; 95% CI, 0.50-0.56), and regional LNE, especially when more than 10 lymph nodes were examined (HR, 0.73; 95% CI, 0.69-0.77), were associated with better long-term OS (P < .001). Pneumonectomy was not associated with reduced mortality risk when 0 nodes were examined (HR for stage T1, 1.43; 95% CI, 0.67-3.06; P = .35; HR for stage T2-T3, 0.62; 95% CI, 0.34-1.13; P = .12) or when more than 15 nodes were examined for stage T1 disease in patients younger than 80 years (HR, 0.77; 95% CI, 0.54-1.09; P = .14) or when patients aged 80 years or older received regional LNE of any extent (>15 nodes examined: HR for stage T1, 0.65; 95% CI, 0.16-2.64; P = .54; HR for stage T2-T3, 0.90; 95% CI, 0.50-1.60; P = .71). Less extensive surgery was not associated with improved OS when 0 nodes were examined in patients aged 80 years or older with stage T2 to T3 tumors (HR for lobectomy, 0.90; 95% CI, 0.65-1.25; P = .53) and in selected operable patients older than 75 years with stage T1 tumors (HR for lobectomy, 1.07; 95% CI, 0.57-2.00; P = .84). Conclusions and Relevance: This study found that, overall, surgery coupled with regional LNE of appropriate extent was associated with the best long-term OS in patients with ES NSCLC.

Comparison of photon volumetric modulated arc therapy, intensity-modulated proton therapy, and intensity-modulated carbon ion therapy for delivery of hypo-fractionated thoracic radiotherapy.

PURPOSE: The aim of the present study was to compare the dose distribution generated from photon volumetric modulated arc therapy (VMAT), intensity modulated proton therapy (IMPT), and intensity modulated carbon ion therapy (IMCIT) in the delivery of hypo-fractionated thoracic radiotherapy. METHODS AND MATERIALS: Ten selected patients who underwent thoracic particle therapy between 2015 and 2016 were re-planned to receive a relative biological effectiveness (RBE) weighted dose of 60 Gy (i.e., GyE) in 15 fractions delivered with VMAT, IMPT, or IMCIT with the same optimization criteria. Treatment plans were then compared. RESULTS: There were no significant differences in target volume dose coverage or dose conformity, except improved D95 was found with IMCIT compared with VMAT (p = 0.01), and IMCIT was significantly better than IMPT in all target volume dose parameters. Particle therapy led to more prominent lung sparing at low doses, and this result was most prominent with IMCIT (p < 0.05). Improved sparing of other thoracic organs at risk (OARs) was observed with particle therapy, and IMCIT further lowered the D1cc and D5cc for major blood vessels, as compared with IMPT (p = 0.01). CONCLUSION: Although it was comparable to VMAT, IMCIT led to significantly better tumor target dose coverage and conformity than did IMPT. Particle therapy, compared with VMAT, improved thoracic OAR sparing. IMCIT, compared with IMPT, may further improve normal lung and major blood vessel sparing under limited respiratory motion.