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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.

4D multi-image-based (4DMIB) optimization is a form of robust optimization where different uncertainty scenarios, due to anatomy variations, are considered via multiple image sets (e.g., 4DCT). In this review, we focused on providing an overview of different 4DMIB optimization implementations, introduced various frameworks to evaluate the robustness of scanned particle therapy affected by breathing motion and summarized the existing evidence on the necessity of using 4DMIB optimization clinically. Expected potential benefits of 4DMIB optimization include more robust and/or interplay-effect-resistant doses for the target volume and organs-at-risk for indications affected by anatomical variations (e.g., breathing, peristalsis, etc.). Although considerable literature is available on the research and technical aspects of 4DMIB, clinical studies are rare and often contain methodological limitations, such as, limited patient number, motion amplitude, motion and delivery time structure considerations, number of repeat CTs, etc. Therefore, the data are not conclusive. In addition, multiple studies have found that robust 3D optimized plans result in dose distributions within the set clinical tolerances and, therefore, are suitable for a treatment of moving targets with scanned particle therapy. We, therefore, consider the clinical necessity of 4DMIB optimization, when treating moving targets with scanned particle therapy, as still to be demonstrated., Radiotherapy & Oncology, 169, ISSN:0167-8140, ISSN:1879-0887

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.

Patients with recurrent breast cancer to chest wall, who had previous irradiation, are difficult to manage and have limited options. Several reports described the use of photon therapy, hyperthermia, and brachytherapy. This is a case report of a 72-year-old female with Stage IIIA (pT3N1M0) invasive ductal carcinoma of the right breast status post modified radical mastectomy. The patient developed recurrence to the chest wall and one internal mammary lymph node one year later. She received 3-D conformal photon radiation therapy for this recurrence. Two years later, she had progression of the recurrence at the right chest wall and axillary and internal mammary lymph nodes. She was treated with intensity modulated proton therapy (IMPT) for a total of 6600 cGy in 33 fractions. However, four months later, she was found to have biopsy-proven isolated metastatic disease at her right bicep, which was again treated with IMPT for a dose of 6000 cGy in 20 fractions. Proton beam therapy was used in this case to spare dose to the brachial plexus, heart and lung while optimally irradiating the recurrent tumors. At last follow up, the patient is alive and has been disease free for 39 months. This report describes the technique and dosimetry for this unique case, which also reviewed recent series of re-irradiation using proton beam.

Background: Coronavirus disease 19 carry a high mortality rate among older patients and minorities such as ethnic Africans and Latinos through the induction of a cytokines storm. Many pharmacologic interventions were proposed to improve the mortality rate from normal organ damage such as pneumonia. Low dose whole lung radiotherapy has been used in the past to treat pneumonia and may improve survival through modulation of the inflammatory cytokines. However, there is a lot of controversy about the efficacy and safety of this treatment modality. Thus, a review of the clinical studies using irradiation for COVID-19 pneumonia is needed to answer those questions Methods: A literature search of PubMed and Google Scholar was conducted. Reported studies were analyzed to assess safety, efficacy, and inflammatory biomarkers response following low dose whole lung radiotherapy Results: Patients who required artificial ventilation for COVID-19 did not benefit from low dose whole lung radiotherapy, most likely due to severe lung damage. The inflammatory response may be attenuated after irradiation but it is unclear whether it is independent of the steroid effect. Conclusion: Randomized studies are required to assess the effect low dose whole lung radiotherapy for COVID-19 pneumonia and its anti-inflammatory property. Such studies are needed for emerging countries with limited resources as radiotherapy may be cost-effective to reduce hospital admission and intensive care unit monitoring.

4D multi-image-based (4D

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.

Radiation therapy (RT) is an integral component of potentially curative management of esophageal cancer (EC). However, RT can cause significant acute and late morbidity due to excess radiation exposure to nearby critical organs, especially the heart and lungs. Sparing these organs from both low and high radiation dose has been demonstrated to achieve clinically meaningful reductions in toxicity and may improve long-term survival. Accruing dosimetry and clinical evidence support the consideration of proton beam therapy (PBT) for the management of EC. There are critical treatment planning and delivery uncertainties that should be considered when treating EC with PBT, especially as there may be substantial motion-related interplay effects. The Particle Therapy Co-operative Group Thoracic and Gastrointestinal Subcommittees jointly developed guidelines regarding patient selection, treatment planning, clinical trials, and future directions of PBT for EC.

Objective To describe the development of a virtual reality (VR) treatment for phantom limb pain (PLP) and phantom sensations and provide feasibility data from testing the treatment in a population of veterans. Design & Subjects Fourteen participants completed a baseline visit evaluating their amputation, PLP, and phantom sensations. Subsequently, participants completed a VR treatment modeled after mirror therapy for PLP, navigating in a VR environment with a bicycle pedaler and motion sensor to pair their cadence to a VR avatar. The VR avatar enabled visualization of the participant’s intact phantom limb in motion, a hypothesized mechanism of mirror therapy. Setting Laboratory. Methods Participants completed pre- and post-treatment measures to evaluate changes in PLP, phantom sensations, and rate helpfulness, realism, immersion, adverse experiences, and treatment satisfaction. Results Eight of 14 participants (57.1%) reported PLP pre–VR treatment, and 93% (13/14) reported one or more unpleasant phantom sensations. After treatment, 28.6% (4/14) continued to report PLP symptoms (t[13] = 2.7, P = 0.02, d = 0.53) and 28.6% (4/14) reported phantom sensations (t[13] = 4.4, P = 0.001, d = 1.7). Ratings of helpfulness, realism, immersion, and satisfaction were uniformly high to very high. There were no adverse experiences. Four participants completed multiple VR treatments, showing stable improvements in PLP intensity and phantom sensations and high user ratings. Conclusions This feasibility study of a novel VR intervention for PLP was practical and was associated with significant reductions in PLP intensity and phantom sensations. Our findings support continued research in VR-based treatments in PLP, with a need for direct comparisons between VR and more established PLP treatments.

This is a case report of a male patient with previous radiation for a thymic carcinoma (20 years ago) who presented with a left breast cancer. He underwent a partial mastectomy followed by proton radiation therapy with a dose of 5040 cGy to the whole breast in 28 fractions with simultaneous boost to 5800 cGy to the lumpectomy cavity. Proton beam therapy was used instead of conventional photon radiation therapy to spare the heart and lung and to avoid any previously irradiated areas. This study describes the technique and comparative dosimetry for this case.

Purpose With limited proton therapy (PT) resources, several centers have designed their own decision-making systems for PT slot prioritization. The pediatric population is well recognized for deriving benefits from PT; however, elderly patients are not a focus for PT. When should PT be considered for use in the elderly population? Methods and Materials We performed a pilot survey of 25 international academic radiation oncologists (ROs) who also spend significant amounts of clinical time caring for elderly patients. Results Of the 12 respondents (48%), 58% used photons only, 17% used protons only, and 25% used photons and protons. Their definition of elderly was age ≥70 years. Geriatric evaluation was not systematic. Hypofractionation (60%) and decrease in total dose (50%) were advocated by half the ROs on the basis of age. Target volumes were similar to those in young patients for 80% of ROs. Organs at risk (OARs) associated with vulnerability and constraints to these OARs were considered different for 40% and 10% of ROs, respectively. Priorities for PT were ranked from highest to lowest as follows: survival, toxicity, quality of life, tumor coverage, locoregional control, patient's wish, dose to vulnerable OARs (oral mucosa, esophagus), quality-adjusted life-years, cost, irradiated volume, and integral dose. All ROs considered elderly patients eligible for accrual in clinical trials. Conclusions This snapshot survey showed the current gap between chronological age and eventual PT allocation among some PT centers worldwide. The findings suggest that elderly age may become an even weaker argument against PT in the future. They also point out a lack of a systematic geriatric approach. As PT might be regarded as a relevant therapeutic means in the elderly population to limit the toxicity burden and hospital costs, better guidance to allocate PT for this growing segment of the population is still needed.

Hepatocellular carcinoma (HCC) is aggressive primary malignancy of the liver that most commonly presents late in the disease course. As a result, the majority of patients are not candidates for curative therapies. Locoregional therapies including Yttrium-90 (Y-90) radioembolization play an important role in management of the vast majority of patients with HCC.Patients with unnresectable HCC (n=17) treated with Y-90 radioembolization from 2005 to 2014 were evaluated retrospectively. Data was abstracted from medical records including patient charts, laboratory data, and imaging. Toxicities were recorded using Common Terminology Criteria 3.0. Response was recorded according to modified RECIST (mRECIST) criteria.Seventeen patients received 33 treatments with Y-90 radioembolization. A majority (65%) received TheraSphere with a minority (35%) receiving SIR-Spheres. The median treatment activity delivered was 1.725 gBq (range, 1.4-2.5 gBq). The median treatment dose delivered was 100 Gy (range, 90-120 Gy). The median lung shunt fraction was 2.02% (range, 1.5-4.1%). The most common clinical toxicity among all patients was nausea and vomiting (59%), primarily grade 1 and 2. Other post-treatment findings included abdominal pain (29%), fatigue (53%), and weight loss (18%). One patient developed a grade 5 gastric ulcer after the treatment. A clinical benefit, defined as patients achieving complete response (CR), partial response (PR) or stable disease (SD), was seen in 48% of patients. PR was seen in 24% of cases; progressive disease (PD) was noted in 35%. Patients survived for a median of 8.4 months (range, 1.3 to 21.1 months) after the first radioembolization treatment. Median survival after Y-90 treatment was 8.4 months among patients treated TheraSphere as compared with 7.8 months in patients treated with SIR-Spheres. The mean overall survival from the time of diagnosis was 11.7 months (range, 3.4 to 43.2 months).For patients with unresectable HCC, Y-90 radioembolization is a safe and well-tolerated procedure. Our experience suggests that a significant percentage of patients achieve clinical benefit including many with PR. Survival after treatment from this single-center, transplant center is in line with prior reports. Prospective, randomized data is required to compare radioembolization with other therapies including chemoembolization and systemic therapy with sorafenib.

Conclusion: As the natural history of low-grade breast cancers is long & protracted, these 15-yr outcome results of favorable histology breast cancer subtypes demonstrate that APBI is at least as efficacious as WBI in the setting of breast conservation therapy. More patients and further FU beyond 15 years will be needed to substantiate these findings. Author Disclosure: P.Y. Chen: None. J.L. Wobb: Resident in Radiation Oncology; Beaumont Health System. M. Wallace: None. M.S. Jawad: Resident in Radiation Oncology; Beaumont Health System. H. Ye: None. A. Pietron: None. N. Dekhne: None. D.S. Brabbins: None.