Role Of Proton Beam Therapy Research Articles

Role of Proton Beam Therapy in Spinal Chordomas: A Narrative Review of The Literature.

Chordomas are rare malignant neoplasms arising from vestigial remnants of the embryonic notochord. Approximately 55-70% of chordomas develop within the vertebral column. Their affinity to develop within the bones of the axial skeleton and propensity to locally invade and recur makes them challenging candidates for complete surgical excision. Adjuvant therapies are hence necessary to improve outcomes; for which chemotherapy has been observed to be largely ineffective, owing to the tumour being resistant to it. Radiotherapy is the current adjuvant therapy of choice for chordoma management. Over the years, proton beam therapy (PBT) has been the subject of medical attention, given the dosimetric benefits it confers over traditional radiotherapy, allowing more concentrated radiation to be given to the target of interest and reducing damage to surrounding normal tissue. A review of the current literature reveals PBT offers significantly better outcomes when used as an adjuvant to maximal surgical resection rather than as a definitive therapy.

Current evidence and the potential role of proton beam therapy for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death, and external beam radiation therapy has emerged as a promising approach for managing HCC. Proton beam therapy (PBT) offers dosimetric advantages over X-ray therapy, with superior physical properties known as the Bragg peak. PBT holds promise for reducing hepatotoxicity and allowing safe dose-escalation to the tumor. It has been tried in various clinical conditions and has shown promising local tumor control and survival outcomes. A recent phase III trial demonstrated the non-inferiority of PBT in local tumor control compared to current standard radiofrequency ablation in early-stage HCC. PBT also tended to show more favorable outcomes compared to transarterial chemoembolization in the intermediate stage, and has proven effective in-field disease control and safe toxicity profiles in advanced HCC. In this review, we discuss the rationale, clinical studies, optimal indication, and future directions of PBT in HCC treatment.

Proton beam therapy for extrahepatic biliary tract cancer: Analysis with prospective multi-institutional patients' registration database, Proton-Net.

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 67.5Gy (RBE) (range, 50-72.6Gy) in 25 (22-30 fractions). With a median follow-up of 16.3months, the median survival time was 20.1months 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 (2cm >), and a larger tumor diameter (2cm <) 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.

Proton Beam Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma.

To discuss the role of proton beam therapy (PBT) in the treatment of patients with oropharyngeal squamous cell carcinoma (OPSCC). A review of the pertinent literature. Proton beam therapy likely results in reduced acute and late toxicity as compared with intensity-modulated radiation therapy (IMRT). The extent of the reduced toxicity, which may be modest, depends on the endpoint and technical factors such as pencil beam versus passive scattered PBT and adaptive replanning. The disease control rates after PBT are likely similar to those after IMRT. Proton beam therapy is an attractive option to treat patients with OPSCC. Whether it becomes widely available depends on access.

Redefine the Role of Proton Beam Therapy for the Locally-Advanced Non-Small Cell Lung Cancer Assisting the Reduction of Acute Hematologic Toxicity.

PurposeTo investigate the potential clinical benefit of utilizing intensity-modulated proton therapy (IMPT) to reduce acute hematologic toxicity for locally advanced non-small cell lung cancer (LA-NSCLC) patients and explore the feasibility of a model-based patient selection approach via the normal tissue complication probability (NTCP).MethodsTwenty patients with LA-NSCLC were retrospectively selected. Volumetric modulated arc photon therapy (VMAT) and IMPT plans were generated with a prescription dose of 60 Gy in 30 fractions. A wide range of cases with varied tumor size, location, stations of metastatic lymph nodes were selected to represent the general cancer group. Contouring and treatment planning followed RTOG-1308 protocol. Doses to thoracic vertebral bodies (TVB) and other organ at risks were compared. Risk of grade ≥ 3 acute hematologic toxicity (HT3+) were calculated based on the NTCP model, and patients with a reduction on NTCP of HT3+ from VMAT to IMPT (△NTCP_HT3+) ≥ 10% were considered to ‘significantly benefit from proton therapy.’ResultsCompared to VMAT, IMPT significantly reduced the dose to the TVB, the lung, the heart, the esophagus and the spinal cord. Tumor distance to TVB was significantly associated with △NTCP _HT3+ ≥ 10%. For the patients with tumor distance ≤ 0.7 cm to TVB, the absolute reduction of dose (mean, V30 and V40) to TVB was significantly lower than that in patients with tumor distance > 0.7 cm.ConclusionIMPT decreased the probability of HT3+ compared to VMAT by reducing the dose to the TVB in LA-NSCLC patients. Patients with tumor distance to TVB less than 0.7 cm are likely to benefit most from proton over photon therapy.

E-Survey: Current Status of Proton Beam Therapy in USA

The clinical use of Proton Beam Therapy (PBT) in the management of cancer is increasing worldwide. USA has high number of proton therapy centres and this number is growing with new proton therapy centres under development. This study expresses the views of Proton Therapy experts from 12 US cities based in 9 states with respect to the role of proton therapy in cancer treatment. An E-survey was conducted to assess clinical, technical, educational, and organizational resources and strategies in US -based Proton Beam Therapy facilities and to recognize patters of practice. The E-survey attempted to identify tumours which are more likely to benefit from Proton beam Therapy compared to Photon based Therapy. The role of Proton Beam Therapy in Breast, Brain and Lung cancers was also studied. The study also intended to find what improvements are needed to ensure efficient treatment planning, delivery and dosimetry. This is the first study of its kind in USA.

Current role of proton beam therapy in patients with hepatocellular carcinoma

Current role of proton beam therapy in patients with hepatocellular carcinoma

When the World Throws You a Curve Ball: Lessons Learned in Breast Cancer Management.

In the care of patients with operable breast cancer, there has been a shift toward increasing use of neoadjuvant therapy. There are benefits to neoadjuvant therapy, such as monitoring for response, as well as an increased rate of breast conservation and reduction of potential morbidity associated with breast surgery, including axillary management. Among patients with highly proliferative tumors, such as HER2-positive or triple-negative breast cancer, those with residual disease are at higher risk of recurrence, which informs the recommended systemic therapy in the adjuvant setting. For instance, in patients with residual disease after neoadjuvant chemotherapy and HER2-targeted therapy, there is a role for adjuvant trastuzumab emtansine for those with residual disease at the time of surgery. The same holds true regarding the role of adjuvant capecitabine in patients with residual disease after neoadjuvant chemotherapy. With the added complexities of treating patients in the era of the COVID-19 outbreak, additional considerations are critical, including initiation of surgery within an appropriate time from completion of neoadjuvant therapy. National consensus guidelines on time to surgery must be developed to improve measurement and comparison across systems. In addition, there is emerging radiation treatment management research addressing a number of factors, including hypofractionation, role of proton beam therapy, safe omission of radiotherapy, and preoperative radiotherapy with or without drug combination. In this article, the multidisciplinary approach of treating patients with operable breast cancer is highlighted, with updates and future considerations described.

Survey of clinician opinions on the role of proton beam therapy in Australia and New Zealand.

We surveyed the Australian and New Zealand (ANZ) radiation oncology community to assess their perceptions, understanding and experience of the current role of proton beam therapy (PBT) and the existing referral process to access PBT overseas, ahead of the development of the first PBT centre in Australia. The survey was conducted between September and October 2019 using a 17-question instrument, which was distributed by email to all 632 radiation oncology fellows and trainees listed in the Royal Australian and New Zealand College of Radiologists database. One hundred and one respondents completed the survey, with an overall response rate of 16%. Most respondents were based in Australia (93%), with the majority working in public centres only (59%); 51% were >10years post fellowship and 17% were trainees. Most respondents (76%) reported moderate or high levels of confidence in the role of PBT. Only 28% had previously referred a patient for PBT overseas, with the most common referral indication being chordoma. Of those who had not previously referred a patient, 48% were not convinced about the rationale of PBT over current therapies available locally, 33% were not aware of the referral process, and 24% had concerns about the timeliness of a decision for government-funded PBT abroad. This survey has demonstrated that, although there is reasonable confidence in the role of PBT among ANZ radiation oncologists, there are a number of important aspects of PBT awareness, education and access that need to be developed prior to commencement of PBT in Australia.

Role of Proton Beam Therapy in Current Day Radiation Oncology Practice

Proton beam therapy (PBT), because of its unique physics of no–exit dose deposition in the tissue, is an exciting prospect. The phenomenon of Bragg peak allows protons to deposit their almost entire energy towards the end of the path of the proton and stops any further dose delivery. Braggs peak equips PBT with superior dosimetric advantage over photons or electrons because PBT doesn’t traverse the target/body but is stopped sharply at an energy dependent depth in the target/body. It also has no exit dose. Because of no exit dose and normal tissue sparing, PBT is hailed for its potential to bring superior outcomes. Pediatric malignancies is the most common malignancy where PBT have found utmost application. Nowadays, PBT is also being used in the treatment of other malignancies such as carcinoma prostate, carcinoma breast, head and neck malignancies, and gastrointestinal (GI) malignancies. Despite advantages of PBT, there is not only a high cost of setting up of PBT centers but also a lack of definitive phase-III data. Therefore, we review the role of PBT in current day practice of oncology to bring out the nuances that must guide the practice to choose suitable patients for PBT.

Head and neck sarcomas in adulthood: current trends and evolving management concepts.

Sarcomas are rare, malignant bone and soft-tissue tumours of mesenchymal origin, and their overall incidence accounts for 1% and 0.2%, respectively, of all malignancies. The aim of this article is to provide a reference on the evolving management concepts and trends of treatment of adult sarcomas of the head and neck in a major head and neck sarcoma centre. Early diagnosis remains a challenge due to non-specific symptomatology. Imaging such as ultrasound (US), magnetic resonance (MRI), computed tomography (CT), and positron emission tomography (PET) CT assist with diagnosis and staging, and biopsy is essential for diagnosis, tumour differentiation, and grading. Staging is dependent on histological grade, size of tumour, and metastasis. Sarcomas spread via the haematogenous route. Adequate clearance of locoregional disease and prevention of distant micrometastases are key to improved disease-free survival outcomes so multimodal treatment at a sarcoma reference centre is imperative. In the head and neck, the treatment for most bone sarcomas is neoadjuvant chemotherapy followed by compartmental resection. The interim tumour response to neoadjuvant chemotherapy is evaluated by PET CT and MRI. Heavy-particle therapy (proton beam) in combination with surgery is increasingly being used to treat otherwise unresectable disease, particularly in children. For soft tissue sarcomas of the head and neck, treatment is complex and depends on grade. Surgery is the principle mode of treatment in low-grade tumours that are amenable to resection. High-grade tumours can be treated with neoadjuvant chemotherapy followed by surgery and radiotherapy. In such cases, the response to the chemotherapy might be used as a guide of potential biological aggressiveness, and has an impact on the planning of the operation and the type and extent of radiotherapy. As a general rule, radiotherapy is reserved for high-grade, advanced soft-tissue sarcomas of the head and neck. Those of bone are radioresistant, and radiotherapy is only administered for palliative purposes when no surgical option exists, an exception being Ewing sarcoma. The role of proton beam therapy is promising, but to our knowledge no long-term data currently exist. The survival advantage of innate immune-modulation remains uncertain for disease in the head and neck.

The role of proton beam therapy in the management of elderly breast cancer patients.

Breast cancer is the most common noncutaneous malignancy in women. The prevalence increases with age such that nearly 7% of women in the United States over age 70 will be diagnosed with breast cancer. Radiation therapy (RT) is a standard component of the treatment course for women of all ages with breast cancer. RT is commonly encountered in the adjuvant setting for women with nonmetastatic disease, but also works for disease palliation in women with metastatic or recurrent disease. Different techniques for delivering RT for breast cancer include whole breast irradiation (WBI), accelerated partial-breast irradiation (APBI), and chest wall irradiation. Although these techniques often employ external beam radiation therapy (EBRT) delivered with photons, proton beam radiation therapy (PBRT) may also be used for each of these methods. Dosimetric breast cancer studies demonstrate clinical benefits of PBRT compared to photon EBRT. PBRT reduces the radiation dose delivered to the heart, particularly in women with left-sided breast cancer. This may subsequently reduce cardiac toxicity and associated cardiovascular disease. PBRT minimizes radiation dose to the lung and secondary tissues resulting in reduced pulmonary toxicity and secondary malignancies, respectively. PBRT offers superior target homogeneity and lymphatic coverage possibly leading to a lower risk of disease recurrence. A phase 3 prospective randomized clinical trial is currently being conducted to evaluate the efficacy of PBRT compared to EBRT with photons in patients with stage II–III breast cancer. Patients over age 70 with favorable stage I breast cancer may omit adjuvant RT. Elderly patients who are candidates for WBI, APBI and chest wall irradiation can receive PBRT and enjoy the same aforementioned benefits with potentially less toxicities. PBRT also plays a role in disease palliation and definitive therapy in patients who are not surgical candidates. In the elderly population, screening tests, such as the Timed Up and Go and G-8, can help determine which patients are suitable candidates for PBRT.

Abstract IA31: Radiation therapy in lung cancer: Recent trends and future directions

Abstract Radiation techniques for lung cancer have evolved substantially over the past decade. While previously many patients were treated with 3D conformal therapy, with large uniform margins placed to estimate respiratory motion in the “average” tumor, patients are now simulated with sophisticated, real-time monitoring of internal motion such that treatment volumes can be individualized to maximize normal tissue sparing through image-guided radiation therapy (IGRT). In addition, many patients are now treated with intensity-modulated radiation therapy (IMRT), which has served to drastically improve conformality in select cases and increase the proportion of patients in which high doses are achievable. Concurrent with these advances, proton beam therapy (PBT) has been implemented in a limited number of centers, with the hope of utilizing the dosimetric distribution advantage of the Bragg Peak to further reduce toxicity. The role of PBT in both early-stage and locally advanced non-small cell lung cancer continues to be defined, as results from a phase II multicenter randomized trial predominantly in patients with stage II-III disease did not demonstrate superiority with PBT and concurrent chemotherapy when compared to similar regimens with IMRT. Finally, there have been much data produced with regard to dosing regimens. In early-stage disease, there has been increased implementation of stereotactic ablative body radiation (SABR), with prospective data emerging for both peripheral and central lesions. In the locally advanced setting, results from RTOG 0617 demonstrated no difference when comparing 60 Gy vs. 74 Gy in the setting of chemoradiation. There has also been a trend towards hypofractionation for patients who are unable to tolerate concurrent chemoradiation or those with oligometastatic disease, yet the benefit of hypofractionated radiation sequentially vs. combined modality treatment will need to be further assessed in prospective randomized trials, particularly in the era of immunotherapy. Citation Format: Daniel R. Gomez. Radiation therapy in lung cancer: Recent trends and future directions [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr IA31.

Proton Beam Therapy Alone for Intermediate- or High-Risk Prostate Cancer: An Institutional Prospective Cohort Study.

The role of proton beam therapy (PBT) as monotherapy for localized prostate cancer (PCa) remains unclear. The purpose of this study was to evaluate the efficacy and adverse events of PBT alone for these patients. Between January 2011 and July 2014, 218 patients with intermediate- and high-risk PCa who declined androgen deprivation therapy (ADT) were enrolled to the study and were treated with PBT following one of the following protocols: 74 Gray (GyE) with 37 fractions (fr) (74 GyE/37 fr), 78 GyE/39 fr, and 70 GyE/28 fr. The 5-year progression-free survival rate in the intermediate- and high-risk groups was 97% and 83%, respectively (p = 0.002). The rate of grade 2 or higher late gastrointestinal toxicity was 3.9%, and a significant increased incidence was noted in those who received the 78 GyE/39 fr protocol (p < 0.05). Grade 2 or higher acute and late genitourinary toxicities were observed in 23.5% and 3.4% of patients, respectively. Our results indicated that PBT monotherapy can be a beneficial treatment for localized PCa. Furthermore, it can preserve the quality of life of these patients. We believe that this study provides crucial hypotheses for further study and for establishing new treatment strategies.

Controversies in dose-escalation for locally advanced non-small cell lung cancer and the role of proton beam therapy.

We appreciate the insightful commentary by Drs. Choi and Simone regarding the phase II study of concurrent chemotherapy and dose-escalated proton beam therapy (PBT) for locally advanced non-resected non-small cell lung cancer (NSCLC) (1). We wish to add several discussion points that are in concord with the aforementioned piece.

The role of proton beam therapy for patients with intermediate- and high-risk prostate cancer.

97 Background: Although there are many patterns of treatment in localized prostate caner, proton beam therapy has no definite role in them. We aimed to assess the outcomes of proton beam therapy (PBT) alone for patients with intermediate- and high-risk prostate cancer, and to clarify the role of PBT in the treatments. Methods: Between Jan. 2011 and Sep. 2014, 204 patients with intermediate- and high-risk prostate cancer who declined to receive hormonal treatments until biochemical or clinical recurrence were enrolled in the study. All patients were irradiated a 70-78 GyE in 28-39 fractions, and pre-treatment risk groups were classified in accordance with the D’Amico criteria. The 5-year (biochemical or clinical) recurrence-free survival (RFS), late gastrointestinal (GI) and genitourinary (GU) toxicity (NCI-CTCAE ver.4.0) were evaluated. We conducted a survey on sexual quality of life (QOL) every six months to evaluate any long-term damage to the sexual function using the Expanded Prostate Cancer Index Composite (EPIC). Results: The mean age and the follow-up period were 66 (range: 39-86) and 52 months (range: 24-76 months), respectively. The 5-year RFS rates in intermediate- (n = 112) and high- (n = 92) risk groups were 96.9% and 83.4%, respectively. There was a significant difference between the two groups (p = 0.002). The incidence of grade 2+ GI and GU toxicity were 4% and 3%, respectively. We found a significant difference in the GI toxicity between the two radiation protocols of 78GyE/39fractions (n = 6, 11%) and 70GyE/28fractions (n = 0, 0%) (p &lt; 0.01). A 5.8% decrease in average after adjusting for aging was found in sexual summary score in six years after treatment, which was equivalent to aging of three years. Conclusions: Proton beam therapy alone demonstrated favorable results in patients with intermediate- and high-risk prostate cancer. Although more patients and longer follow-up are necessary to confirm the outcomes, these results suggested a hypothesis that proton beam therapy might not require androgen deprivation therapy in the treatment of localized prostate cancer, which could lead to a possibility of preserving of sexual function. Clinical trial information: MPTRC-N2 and N3.

The role of proton beam therapy in central neurocytoma: A single-institution experience

PurposeCentral neurocytomas (CNs) are rare World Health Organization grade II tumors managed with surgery and radiation therapy. We report our experience in managing CN with proton beam therapy (PBT) when radiation therapy was used. Methods and materialsWe identified 61 patients with pathologically diagnosed CN treated at our institution between 1996 and 2016, of which 24 met inclusion criteria. Patient, tumor, and treatment characteristics are reported in context of progression-free survival and treatment-related adverse events. ResultsOf 24 patients identified, median age at diagnosis was 21 years (range, 14-60). Median maximal tumor diameter was 4.5 cm (range, 1.4-6.8). Eighteen (75%) patients underwent upfront surgery alone. Sixteen (67%) patients received adjuvant or salvage PBT at a median dose of 54 Gy (relative biological effectiveness). Median follow-up was 56 months. Median progression-free survival (PFS) was 61 months. Eleven patients had disease progression with median time to progression of 22 months. Of the 5 patients with gross total resection, 4 experienced local recurrence and had MIB-1 >4% (range, 4.5-30). There was improved PFS with addition of PBT to definitive surgery (log-rank, P = .06); there was no disease progression to date. In patients who experienced disease recurrence/progression, MIB-1 <4% was associated with improved PFS (log-rank, P = .007). All patients tolerated PBT well with toxicities typical for cranial irradiation and with no grade 3+ toxicities. ConclusionIn our cohort, CN with elevated MIB-1 index were at increased risk for disease progression. However, adjuvant radiation therapy appears to effectively prevent failure. PBT toxicities appear to be comparable to if not less than published photon experiences.

The Evolving Role of Proton Beam Therapy for Sarcomas

As an alternative to conventional photon-based radiotherapy, radiation with protons is recognised to offer considerable advantages. Today, central nervous system tumours, various sarcomatous tumours, childhood cancer and head and neck tumours are commonly treated with proton therapy. This review evaluates current data from clinical and dosimetric trials on the treatment of selected sarcomatous tumours like rhabdomyosarcoma, osteosarcoma, chordoma, chondrosarcoma and Ewing sarcoma. Special considerations for paediatric tumours and future prospects of proton therapy are outlined. Proton therapy is already an internal part in the multidisciplinary management of childhood sarcomas in contiguity to sensitive structures, especially at the base of skull, spine and pelvis. It offers special advantages for tumours requiring high-precision radiotherapy, particularly when total resection seems not feasible. Previous and ongoing research is generating evidence for the benefit of protons in sarcoma patients. Up to now, proton therapy has been safely applied with encouraging results. For future research, prospective, multi-institutional, large registries are required to answer open questions. Modern radiotherapy techniques, such as pencil beam scanning and intensity modulation are increasingly established in proton therapy. More research is needed to understand protons' limitations and potential.

ED10.03 New Developments in Radiotherapy of Stage III NSCLC

ED10.03 New Developments in Radiotherapy of Stage III NSCLC

Proton Beam Therapy of Stage II and III Non–Small-Cell Lung Cancer

The present retrospective study assessed the role of proton beam therapy (PBT) in the treatment of patients with Stage II or III non-small-cell lung cancer who were inoperable or ineligible for chemotherapy because of co-existing disease or refusal. Between November 2001 and July 2008, PBT was given to 35 patients (5 patients with Stage II, 12 with Stage IIIA, and 18 with Stage IIIB) whose median age was 70.3 years (range, 47.4-85.4). The median proton dose given was 78.3 Gy (range, 67.1-91.3) (relative biologic effectiveness). Local progression-free survival for Stage II-III patients was 93.3% at 1 year and 65.9% at 2 years during a median observation period of 16.9 months. Four patients (11.4%) developed local recurrence, 13 (37.1%) developed regional recurrence, and 7 (20.0%) developed distant metastases. The progression-free survival rate for Stage II-III patients was 59.6% at 1 year and 29.2% at 2 years. The overall survival rate of Stage II-III patients was 81.8% at 1 year and 58.9% at 2 years. Grade 3 or greater toxicity was not observed. A total of 15 patients (42.9%) developed Grade 1 and 6 (17.1%) Grade 2 toxicity. PBT for Stage II-III non-small-cell lung cancer without chemotherapy resulted in good local control and low toxicity. PBT has a definite role in the treatment of patients with Stage II-III non-small-cell lung cancer who are unsuitable for surgery or chemotherapy.