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PDF file, 1232K, SRA/CD204-targeted radio-immunotherapy enhances cytolytic activity of effector T cells.

Image guidance for radiation therapy can improve the accuracy of the delivery of radiation, leading to an improved therapeutic ratio. Proton radiation is able to deliver a highly conformal dose to a target due to its advantageous dosimetric properties, including the Bragg peak. Proton therapy established the standard for daily image guidance as a means of minimizing uncertainties associated with proton treatment. With the increasing adoption of the use of proton therapy over time, image guidance systems for this modality have been changing. The unique properties of proton radiation present a number of differences in image guidance from photon therapy. This paper describes CT and MRI-based simulation and methods of daily image guidance. Developments in dose-guided radiation, upright treatment, and FLASH RT are discussed as well.

PDF file, 662K, SRA/CD204 silencing in DCs increases IFN-γ production by CD8+ cells, not CD4+ cells, after combinatorial therapy of RT and in situ DC vaccination.

Gastrointestinal (GI) cancers are among the leading causes of cancer-related mortality and have traditionally been treated using a combination of surgical resection and chemoradiotherapy (CRT). While the introduction of immunotherapies over the last decade have dramatically changed the treatment landscape for some GI malignancies, including esophageal, gastric, and colorectal cancer, treatment resistance remains a major unaddressed obstacle for many patients. There has thus been emerging interest in determining the optimal treatment strategy for the delivery of immunotherapy in combination with traditional therapies. In this regard, a growing number of preclinical and clinical studies have suggested that combining radiation therapy (RT) with immunotherapy may work synergistically to improve treatment response through amplification of the abscopal effect. In this review, we discuss the rationale for RT in combination with immunotherapy. We further discuss how this knowledge may lead to a paradigm shift in the application of RT and highlight remaining issues pertaining to the delivery of combination therapy.

Background: There is a rapidly increasing population referring themselves for lung cancer screening in China. This study sought to investigate the clinicopathological characteristics of self-referred versus symptom-driven detection of lung cancer, and the consequences of self-referred behavior in patients ineligible for LDCT screening. Methods: A total of 58,433 patients receiving surgical treatment for primary lung cancer, between 1989 and 2018 were included, 61.2% of whom were self-referred. Overdiagnosis refers to detection of adenocarcinoma in situ (AIS) by self-referred screening. Findings: Lung cancers detected via self-referral rose from 9.5% (n=30) in 1989 to 81.2% (n=10127) in 2018, contributing to a significant decrease in tumor size (AAPC, self-referred: -3.89% versus symptom-driven: -2.72%) and a wider application of wedge resection in tumor ≤1cm (self-referred: 39.9% versus symptom-driven: 30.6%, p<0.001). Self-referred screening independently improved lung cancer survival (HR: 0.74; 95%CI: 0.71-0.78). The proportion of patients eligible for LDCT screening decreased from 41.5% to 10.2% (AAPC: -5.13%), mainly caused by self-referred screening population. Shifts in histology (adenocarcinoma) and stage (stage-I) attributed to self-referred screening were more prevalent in patients ineligible for LDCT screening. Self-referral-associated overdiagnosis rate was 22.0%, dependent on tumor size (≤1cm, 1-2cm, and 2-3cm: 50.5%, 5.3%, and 0.3%, respectively). Interpretation: Increases in self-referred screening have contributed to an early detection, less extensive resection, and improved survival of lung cancer. The favorable shift in cancer stage was more pronounced among self-referred patients who were ineligible for screening, suggesting an opportunity for improved screening protocols. However, the risk of overdiagnosis should not be disregarded. Funding: This study was supported by the National Natural Science Foundation of China (Grant No. 82172848).Declaration of Interest: René Horsleben Petersen reports speaker fee from Medtronic, AMBU, AstraZeneca and Medela and Advisory Board member: AstraZeneca, Roche and MSD. Dominique Gossot reports speaker fee from Medtronic and Johnson&Johnson, and consultant fee from Delacroix- Chevalier. Other authors have no conflicts of interest to declare.Ethical Approval: The study protocol was approved by the Institutional Review Broad of Shanghai Pulmonary Hospital, Tongji University (no. K21-377), and patients informed consent was waived because of its retrospective nature.

PDF file, 1337K, The effect of combined RT and in situ DC vaccination on tumor-infiltrating CD4+ and CD11c+ cells.

PDF file, 1187K, DC-SRA shRNA vaccination following RT upregulates Granzyme B expression in tumor-infiltrating CD8+ cells.

PDF file, 1186K, Silencing SRA/CD204 enhances an inflammatory response in DCs stimulated with radiation-treated tumor cells.

Background Perianal basal cell carcinoma (BCC) is very rare and estimated to account for 0.08% of all BCC and 0.02% of all anorectal neoplasms. Perianal lesions are more likely to be squamous cell carcinoma (SCC) as BCC usually develops on areas of skin exposed to ultraviolet (UV) light such as the face and arms. Proper diagnosis with the assistance of immunohistochemistry (IHC) stains to distinguish the two entities can help inform the suitable course of treatment. Case Description Our case is an 82-year-old male with a history of cutaneous BCC on the arms and trunk presenting with a symptomatic perianal lesion. Initial biopsy demonstrated BCC with subsequent IHC studies differentiating from basaloid SCC. Standard treatment includes wide local excision (WLE) but given his poor performance status, radiation only was recommended. He was successfully treated and tolerated 30 Gy in 5 daily fractions. Conclusions Radiation only is a unique and feasible non-surgical treatment for basosquamous carcinoma of the anus.

Background: Epidermal growth factor receptor (EGFR) is overexpressed in pancreatic cancer. EGFR expression plays a potentially important role in modulation of tumor sensitivity to either chemotherapy or radiotherapy. Erlotinib is a receptor tyrosine kinase inhibitor with specificity for EGFR/HER1. A phase II trial was conducted to explore the efficacy of a regimen utilizing erlotinib and proton therapy. Methods: Patients with unresectable or borderline resectable non-metastatic adenocarcinoma of the pancreas were included. Patients received 8-week systemic treatment with gemcitabine 1,000 mg/m(2) and erlotinib 100 mg (GE). If there was no evidence of metastatic disease after GE, then patients preceded with proton therapy to 50.4 Gy in 28 fractions with concurrent capecitabine 825 mg/m(2) (CPT). This was followed with oxaliplatin 130 mg/m(2) and capecitabine 1,000 mg/m2 (CapOx) for 4 cycles. The primary study objective was 1-year overall survival (OS). The benchmark was 43% 1-year survival as demonstrated in RTOG/NRG 98-12. The Kaplan-Meier method was used to estimate the one-year OS and the median OS and progression-free survival (PFS). Results: The study enrolled 9 patients ages 47-81 years old (median 62) between January 2013 and March 2016, when the trial was dosed due to low patient accrual. The 1-year OS rate was 55.6% (95% CI: 31% to 99%). The median OS was 14.1 months (95% CI: 11.4-NE) and the median PFS was 10.8 months (95% CI: 7.44-NE). A majority of patients completed CPT and GE, but only 33.3% completed the four cycles of CapOx. A third of patients experienced grade 3 toxicities, which were all hepatic along with one patient who also had grade 3 diarrhea. There were no grade 4 or 5 toxicities. Four patients were enrolled with borderline resectable disease, three of which were eligible for pancreaticoduodenectomy after GE and CPT treatment. One of two patients who underwent resection had a negative margin. Conclusions: This regimen for locally advanced pancreatic cancer (LAPC) exceeded the pre-specified benchmark and was safe and well tolerated. Additional investigations utilizing more current systemic treatment regimens with proton therapy are warranted.

PURPOSE:To develop a multidisciplinary consensus for high quality multidisciplinary implementation of brachytherapy using Yttrium-90 (90Y) microspheres transarterial radioembolization (90Y TARE) for primary and metastatic cancers in the liver.METHODS AND MATERIALS:Members of the American Brachytherapy Society (ABS) and colleagues with multidisciplinary expertise in liver tumor therapy formulated guidelines for 90Y TARE for unresectable primary liver malignancies and unresectable metastatic cancer to the liver. The consensus is provided on the most recent literature and clinical experience.RESULTS:The ABS strongly recommends the use of 90Y microsphere brachytherapy for the definitive/palliative treatment of unresectable liver cancer when recommended by the multidisciplinary team. A quality management program must be implemented at the start of 90Y TARE program development and follow-up data should be tracked for efficacy and toxicity. Patient-specific dosimetry optimized for treatment intent is recommended when conducting 90Y TARE. Implementation in patients on systemic therapy should account for factors that may enhance treatment related toxicity without delaying treatment inappropriately. Further management and salvage therapy options including retreatment with 90Y TARE should be carefully considered.CONCLUSIONS:ABS consensus for implementing a safe 90Y TARE program for liver cancer in the multidisciplinary setting is presented. It builds on previous guidelines to include recommendations for appropriate implementation based on current literature and practices in experienced centers. Practitioners and cooperative groups are encouraged to use this document as a guide to formulate their clinical practices and to adopt the most recent dose reporting policies that are critical for a unified outcome analysis of future effectiveness studies.

BACKGROUND:To report on our institutional experience using Proton stereotactic body radiation therapy (SBRT) for patients with liver metastases.METHODS:All patients with liver metastases treated with Proton SBRT between September 2012 and December 2017 were retrospectively analyzed. Local control (LC) and overall survival (OS) were estimated using the Kaplan-Meier method calculated from the time of completion of Proton SBRT. LC was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1). Toxicity was graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.RESULTS:Forty-six patients with 81 lesions were treated with Proton SBRT. The median age was 65.5 years old (range, 33-86 years) and the median follow up was 15 months (range, 1-54 months). The median size of the gross tumor volume (GTV) was 2.5 cm (range, 0.7-8.9 cm). Two or more lesions were treated in 56.5% of patients, with one patient receiving treatment to a total of five lesions. There were 37 lesions treated with a biologically effective dose (BED) ≤60, 9 lesions with a BED of 61-80, 22 lesions with a BED of 81-100, and 13 lesions with a BED >100. The 1-year and 2-year LC for all lesions was 92.5% (95% CI, 82.7% to 96.8%). The grade 1 and grade 2 toxicity rates were 37% and 6.5%, respectively. There were no grade 3 or higher toxicities and no cases of radiation-induced liver disease (RILD).CONCLUSIONS:Proton SBRT for the treatment of liver metastases has promising LC rates with the ability to safely treat multiple liver metastases. Accrual continues for our phase II trial treating liver metastases with Proton SBRT to 60 GyE (Gray equivalent) in 3 fractions.

Introduction Retroperitoneal sarcoma (RPS) is a rare malignancy, and curative resection is considered the main therapy. Use of chemotherapy and/or radiation in addition to surgery (multimodality therapy) is controversial. Objective To determine treatment factors that influence overall survival in RPS. Methods This retrospective Institutional Review Board-approved study identified patients with RPS treated at a single institution between 2000 and 2017. Patient, tumor, and treatment modalities were collected. Prism (v.8.2.1) was used to calculate Kaplan-Meier survival curves. Results There were 695 patients with sarcoma between 2000 and 2017, and 61 adults had RPS. The mean age was 59 (range 31-86) years, with 57.4% females (n = 35). Patients were 68.9% Caucasian (n = 42), 21.3% Hispanic (n = 13), 8.2% black (n = 5), and 1.6% Asian (n = 1). There were 4 patients who had neoadjuvant therapy (chemotherapy, n = 3; radiation, n = 2) and 17 who had adjuvant therapy (chemotherapy, n = 6; radiation, n = 14). There was no significant difference in survival between the groups who received multimodality therapy compared to surgery alone. There was a significant improvement in the median overall survival for patients who underwent one or multiple surgeries (P < .05). Conclusions These institutional data suggest that treatment factors associated with overall survival included multiple resections. Use of multimodality therapy was low and did not influence overall survival in patients with RPS compared to surgery alone.

Background Recent randomized controlled trials have failed to show a survival difference between adjuvant chemotherapy (CT) and adjuvant chemoradiotherapy (CRT) in patients with resected gastric cancer (GC). However, a subset of patients with lymph node (LN) positive disease may still benefit from CRT. Additional evidence is needed to help guide physicians in identifying patients in whom CRT should be considered. Our objective was then to compare survival outcomes based on lymph node ratio (LNR) (ratio of metastatic to harvested LNs) for patients with gastric and gastroesophageal junction (GEJ) adenocarcinoma treated with surgery and either CT or CRT. Methods This retrospective population-based study used California Cancer Registry (CCR) data from 2004 to 2013. It included 1,493 patients diagnosed with stage IB-III gastric/GEJ adenocarcinoma and treated with CT or CRT following total or partial gastrectomy. Overall survival (OS) was the primary outcome and GC-specific survival was secondary. Mortality hazards ratios (HR) for these outcomes were computed using propensity score weighted Cox regression models, stratified by LNR strata categories as 0%, 1-9%, 10-25% and >25%. Results Out of 1,493 patients that met inclusion criteria, 462 were treated with CT while 1,031 received CRT. Median follow-up for all subjects was 76 months and median survival was 54 months for CRT and 35 for the CT cohort, P<0.001. Compared to CT, CRT was associated with improved survival among patients with LNR of 10-25% [HR =0.62 (95% CI, 0.46-0.83)] and >25% [HR =0.67 (95% CI, 0.56-0.80)]. Similar findings were observed for GC-specific survival and for analyses limited to patients that had at least 15 LNs evaluated. Conclusions LNR appears to be a simple and readily available measure that could be used in treatment planning for resected GC. CRT offers significant survival advantage over CT among patients with high LN disease burden (LNR of ≥10%).

To determine the maximum tolerated dose (MTD) of stereotactic body proton therapy (SBPT) for liver metastases in anticipation of a subsequent phase II study. Although phase I studies have shown safety with photon based treatments, similar clinical safety profile and tolerability with proton based therapy has not been reported. An IRB approved phase I clinical trial was conducted. Eligible patients had 1-3 liver metastases measuring less than 5cm, and no CNS metastases, tense ascites requiring frequent paracentesis or metastases location within 2cm of the GI tract. The initial cohort received 36 GyE to the planning target volume (PTV) in 3 fractions. Subsequent cohorts received 48 GyE in 3 fractions and finally 60 GyE in 3 fractions, the final chosen maximum dose. At least 700mL of normal liver had to receive <15 GyE. Dose-limiting toxicity (DLT) included acute grade 3 liver, intestinal or spinal cord toxicity or any grade 4 toxicity. The MTD is defined as the dose level below that which results in DLT in 2 or more of the 6 patients in the highest dose level cohort. Nine patients were enrolled (6 male, 3 female): median age 64 years (range, 33-77 years); median gross tumor volume 11.1 ml (range, 2.14-89.3 ml); most common primary site, colorectal (5 patients). Four patients had multiple tumors. No patient experienced a DLT and dose was escalated to 60 GyE in 3 fractions without reaching MTD. The only toxicity within 90 days of completion of treatment was one patient with a grade 1 skin hyperpigmentation without tenderness or desquamation. Two patients in the first cohort had local recurrence and repeat SBPT was done to previously treated lesions without any reported toxicities. Biologically ablative SBPT doses are well tolerated in patients with limited liver metastases with no patients experiencing any grade 2+ acute toxicity. Results from this trial provide the grounds for an ongoing phase II SBPT study of 60 GyE over 3 fractions for liver metastases.

Gastrointestinal Malignancies, pp. 637-646 (2015) No AccessChapter 23: Proton Therapy: A New Dawn for Gastrointestinal Cancer TreatmentGary Y. Yang and Jerome C. LandryGary Y. Yang and Jerome C. Landryhttps://doi.org/10.1142/9789814618991_0023Cited by:0 PreviousNext AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsRecommend to Library ShareShare onFacebookTwitterLinked InRedditEmail Abstract: The following sections are included: What is New Introduction Proton Beam Therapy Proton Therapy for Treating Gastrointestinal Malignancy Take Home Messages References FiguresReferencesRelatedDetails Gastrointestinal MalignanciesMetrics History PDF download

BACKGROUND:Exploiting biologic imaging, studies have been performed to boost dose to gross intraprostatic tumor volumes (GTV) while reducing dose elsewhere in the prostate. Interest in proton beams has increased due to superior normal-tissue sparing they afford. Our goal was to dosimetrically compare 3D conformal proton boost plans with intensity-modulated radiation therapy (IMRT) plans with respect to target coverage and avoiding organs at risk.METHODS:Treatment planning computer tomography scans of ten patients were selected. For each patient, two hypothetical but realistic GTVs each with a fixed volume were contoured in different anatomical locations of the prostate. IMRT and proton beam plans were created with a prescribed dose of 50.4 Gy to the initial planning target volume (PTV) including the PTV of the seminal vesicles (PSV), 70.2 Gy to the PTV of the prostate (PPS), and 90 Gy to the PTV of the gross tumor volumes (PGTVs). For proton plans, uncertainties of range and patient setup were accounted for; apertures were adjusted until the dose-volume coverage of PTVs matched that of the IMRT plan. For both plans, prescribed PTV doses were made identical to allow for comparing normal-tissue doses.RESULTS:Protons delivered more homogeneous but less conformal doses to PGTVs than IMRT did and comparable doses to PSV and PPS. Volumes of bladder and rectum receiving doses higher than 65 Gy were similar for both plans. However, volumes receiving less than 65 Gy were significantly reduced, i.e., protons reduced integral dose by 45.6 % and 26.5 % for rectum and bladder, respectively. This volume-sparing was also seen in femoral heads and penile bulb.CONCLUSIONS:Protons delivered comparable doses to targets in dose homogeneity and conformity and spared normal tissues from intermediate-to-low doses better than IMRT did. Further improvement of dose sparing and changes in homogeneity and conformity may be achieved by reducing proton range uncertainties and from implementing intensity modulation.