scholarly journals Combination of Proton Therapy and Radionuclide Therapy in Mice: Preclinical Pilot Study at the Paul Scherrer Institute

Pharmaceutics ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 450 ◽  
Author(s):  
Cristina Müller ◽  
Maria De Prado Leal ◽  
Marco D. Dominietto ◽  
Christoph A. Umbricht ◽  
Sairos Safai ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Solid Tumors ◽  
Proton Therapy ◽  
Radionuclide Therapy ◽  
Folate Receptor ◽  
Tumor Model ◽  
Treatment Modalities ◽  
Growth Delay ◽  
Future Research ◽  
High Dose

Proton therapy (PT) is a treatment with high dose conformality that delivers a highly-focused radiation dose to solid tumors. Targeted radionuclide therapy (TRT), on the other hand, is a systemic radiation therapy, which makes use of intravenously-applied radioconjugates. In this project, it was aimed to perform an initial dose-searching study for the combination of these treatment modalities in a preclinical setting. Therapy studies were performed with xenograft mouse models of folate receptor (FR)-positive KB and prostate-specific membrane antigen (PSMA)-positive PC-3 PIP tumors, respectively. PT and TRT using 177Lu-folate and 177Lu-PSMA-617, respectively, were applied either as single treatments or in combination. Monitoring of the mice over nine weeks revealed a similar tumor growth delay after PT and TRT, respectively, when equal tumor doses were delivered either by protons or by β¯-particles, respectively. Combining the methodologies to provide half-dose by either therapy approach resulted in equal (PC-3 PIP tumor model) or even slightly better therapy outcomes (KB tumor model). In separate experiments, preclinical positron emission tomography (PET) was performed to investigate tissue activation after proton irradiation of the tumor. The high-precision radiation delivery of PT was confirmed by the resulting PET images that accurately visualized the irradiated tumor tissue. In this study, the combination of PT and TRT resulted in an additive effect or a trend of synergistic effects, depending on the type of tumor xenograft. This study laid the foundation for future research regarding therapy options in the situation of metastasized solid tumors, where surgery or PT alone are not a solution but may profit from combination with systemic radiation therapy.

scholarly journals Indications of Peptide Receptor Radionuclide Therapy (PRRT) in Gastroenteropancreatic and Pulmonary Neuroendocrine Tumors: An Updated Review

2021 ◽  
Vol 10 (6) ◽  
pp. 1267
Author(s):  
Baptiste Camus ◽  
Anne-Ségolène Cottereau ◽  
Lola-Jade Palmieri ◽  
Solène Dermine ◽  
Florence Tenenbaum ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Radionuclide Therapy ◽  
Somatostatin Receptors ◽  
Peptide Receptor Radionuclide Therapy ◽  
Phase Iii ◽  
Treatment Modalities ◽  
High Dose ◽  
Double Dose ◽  
Peptide Receptor ◽  
Phase Iii Study

Radionuclide therapy for neuroendocrine tumors is a form of systemic radiotherapy that allows the administration of targeted radionuclides into tumor cells that express a large quantity of somatostatin receptors. The two most commonly used radio-peptides for radionuclide therapy in neuroendocrine tumors are 90Y-DOTATOC and 177Lu-DOTATATE. Radio-peptides have been used for several years in the treatment of advanced neuroendocrine tumors. Recently, the randomized Phase III study NETTER-1 compared177Lu-DOTATATE versus high-dose (double-dose) octreotide LAR in patients with metastatic midgut neuroendocrine tumors, and demonstrated its efficacy in this setting. Strong signals in favor of efficiency seem to exist for other tumors, in particular for pancreatic and pulmonary neuroendocrine tumors. This focus on radionuclide therapy in gastroenteropancreatic and pulmonary neuroendocrine tumors addresses the treatment modalities, the validated and potential indications, and the safety of the therapy.

High-dose rate intraoperative radiation therapy for pediatric solid tumors

1998 ◽  
Vol 30 (1) ◽  
pp. 34-39 ◽  
Author(s):  
Thomas E. Merchant ◽  
Michael J. Zelefsky ◽  
John M. Sheldon ◽  
Michael B. LaQuaglia ◽  
Louis B. Harrison
Keyword(s):  
Radiation Therapy ◽  
Dose Rate ◽  
Solid Tumors ◽  
High Dose Rate ◽  
Intraoperative Radiation Therapy ◽  
High Dose ◽  
Intraoperative Radiation ◽  
Pediatric Solid Tumors

Stereotactic Ablative Radiation Therapy as a Potential Curative Treatment in Duodenal Adenocarcinoma: A Case Report

2017 ◽  
Vol 103 (1_suppl) ◽  
pp. S31-S33
Author(s):  
Francesco Maria Aquilanti ◽  
Maria Cristina Barba ◽  
Federico Bianciardi ◽  
Barbara Tolu ◽  
Barbara Nardiello ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Small Bowel ◽  
Large Mass ◽  
Treatment Modalities ◽  
Tumor Control ◽  
High Dose ◽  
Toxicity Profile ◽  
Upper Abdominal ◽  
Cancer Experience ◽  
Stereotactic Ablative Radiation Therapy

Purpose One of the rarest gastrointestinal neoplasm is small bowel cancer. Experience with its treatment modalities is limited. Stereotactic ablative radiation therapy (SABR) has improved, with image-guided radiation therapy becoming a curative option in many tumors. Especially when surgery cannot be performed due to comorbidities, SABR provides a good toxicity profile and an excellent tumor control rate owing to its specific schedule: high dose on a limited and well-defined area. Methods An 83-year-old man had arterial hypertension and congestive cardiomyopathy, with recent history of upper abdominal pain, weight loss over 10 kg, and progressive severe fatigue. The patient underwent endoscopy that showed a large mass partially obstructing the second part of the duodenum; a biopsy revealed a moderately differentiated adenocarcinoma. A staging CT scan confirmed localized disease. Due to the patient's age and comorbidities, a SABR was proposed as the preferred treatment. In order to localize the tumor during radiotherapy sessions, surgical clips were placed endoscopically next to the lesion as fiducial markers. The patient received 25 Gy in 5 fractions on alternate days. Results Resolution of duodenal obstruction and bleeding lasted for 14 months. The patient died of myocardial infarction. Conclusions This case suggests that SABR could have a role in the palliative treatment of small bowel cancers, with good toxicity profile, particularly in patients for whom surgical treatment is not a viable option.

scholarly journals Biological and Mechanical Synergies to Deal With Proton Therapy Pitfalls: Minibeams, FLASH, Arcs, and Gantryless Rooms

2021 ◽  
Vol 10 ◽  
Author(s):  
Alejandro Mazal ◽  
Juan Antonio Vera Sanchez ◽  
Daniel Sanchez-Parcerisa ◽  
Jose Manuel Udias ◽  
Samuel España ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Proton Therapy ◽  
Target Volume ◽  
High Dose Rate ◽  
Clinical Applications ◽  
High Dose ◽  
Beam Path ◽  
Entrance Dose ◽  
Dose Constraints ◽  
Very High

Proton therapy has advantages and pitfalls comparing with photon therapy in radiation therapy. Among the limitations of protons in clinical practice we can selectively mention: uncertainties in range, lateral penumbra, deposition of higher LET outside the target, entrance dose, dose in the beam path, dose constraints in critical organs close to the target volume, organ movements and cost. In this review, we combine proposals under study to mitigate those pitfalls by using individually or in combination: (a) biological approaches of beam management in time (very high dose rate “FLASH” irradiations in the order of 100 Gy/s) and (b) modulation in space (a combination of mini-beams of millimetric extent), together with mechanical approaches such as (c) rotational techniques (optimized in partial arcs) and, in an effort to reduce cost, (d) gantry-less delivery systems. In some cases, these proposals are synergic (e.g., FLASH and minibeams), in others they are hardly compatible (mini-beam and rotation). Fixed lines have been used in pioneer centers, or for specific indications (ophthalmic, radiosurgery,…), they logically evolved to isocentric gantries. The present proposals to produce fixed lines are somewhat controversial. Rotational techniques, minibeams and FLASH in proton therapy are making their way, with an increasing degree of complexity in these three approaches, but with a high interest in the basic science and clinical communities. All of them must be proven in clinical applications.

17 High-dose rate intra-operative radiation therapy for pediatric solid tumors

1996 ◽  
Vol 39 ◽  
pp. S5 ◽  
Author(s):  
T.E. Merchant ◽  
M.J. Zelefsky ◽  
J.M. Sheldon ◽  
M.B. LaQuaglia ◽  
L.B. Harrison
Keyword(s):  
Radiation Therapy ◽  
Dose Rate ◽  
Solid Tumors ◽  
High Dose Rate ◽  
High Dose ◽  
Pediatric Solid Tumors

Therapy-related myeloid leukemia following Pleuropulmonary blastoma: A case report

2022 ◽  
Author(s):  
Nahid Reisi ◽  
Pardis Nematolahy
Keyword(s):  
Radiation Therapy ◽  
Myeloid Leukemia ◽  
Lung Neoplasm ◽  
Treatment Modalities ◽  
Pleuropulmonary Blastoma ◽  
Secondary Malignancy ◽  
High Dose ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Response To Chemotherapy

The development of secondary malignancy (SM) is the most worrisome long-term complication of childhood cancer. Acute myeloid leukemia is the most prevalent neoplasm that occurs after treatment with alkylating agents and topoisomerase II inhibitors. Pleuropulmonary blastoma (PPB) is a rare lung neoplasm in children. Type II and type III of this cancer are markedly aggressive and have a recurrent nature. Chemotherapy, radiation therapy, and hematopoietic stem cell transplant (HSCT) are treatment modalities that make these patients prone to secondary malignancy. Here was presented and discussed a case of myeloid leukemia 3.5 years after treatment of Pleuropulmonary blastoma in a 5.5-year-old boy who was a candidate for high dose chemotherapy and autologous stem cells transplant (auto-SCT) because of frequent recurrence and lack of response to chemotherapy and radiation therapy. It seems this is the first reported case of therapy-related myeloid leukemia (t-AML) after PPB in children. Awareness of the creation of this complication following administration of cytotoxic therapies in the treatment of solid tumors will increase physician attention in the selection of treatment modality as well as the counseling of patients at the time of diagnosis.

The potential role of modern radiotherapy techniques in the treatment of malignant spinal cord compression: a dose planning study

2015 ◽  
Vol 14 (4) ◽  
pp. 418-424 ◽  
Author(s):  
Lotte S. Fog ◽  
Deborah Schut ◽  
Per Sjøgren ◽  
Marianne C. Aznar
Keyword(s):  
Spinal Cord ◽  
Radiation Therapy ◽  
Dose Reduction ◽  
Spinal Cord Compression ◽  
Cord Compression ◽  
Treatment Modalities ◽  
High Dose ◽  
Lumbar Region ◽  
Field Technique ◽  
Time Required

AbstractAimTo investigate the doses given to the kidneys and the small intestines for three radiation therapy techniques [anterior–posterior (APPA) fields, three fields and volumetric-modulated arc therapy (VMAT)] for spinal cord compression (SCC) patients with metastatic disease in the lower thoracic or lumbar spine and to monitor the time spent by clinicians and dose planners.IntroductionRadiation therapy is one of the main treatment modalities for SCC. Typical palliative radiation therapy techniques have used APPA fields or a three-field technique.However, as delivery techniques have evolved dramatically over the past decades, VMAT has gained wide acceptance. VMAT allows for a dose reduction in the organs at risk. Such a dose reduction may result in less toxicity.The use of the VMAT technique may require more time for contouring and planning compared with the APPA and three-field techniques. Any potential dosimetric benefit of VMAT must not be outweighed by large amounts of extra time spent by clinicians and dose planners.Materials and methodsFor 20 patients treated with radiation therapy for SCC at our hospital, we created a VMAT plan, and the more traditionally used APPA and three-field plans. The mean kidney doses and the volume of bowel, which received 20 Gy, were extracted for each plan. The correlations between parameters for three techniques were determined.Furthermore, the time required for contouring targets for five patients; and the time required to plan five patients, was recorded.ResultsVMAT lead to the most conformal distributions: the high-dose areas were restricted to the target volume, whereas the healthy tissue, especially the bowel, received a lower dose. In contrast, the APPA plan lead to a larger volume of bowel being irradiated, whereas the three-field technique spared the bowel at the expense of a higher dose to the kidneys.The average contouring time was 16 minutes, the average planning time was 38 minutes.ConclusionPatients treated for SCC in the lower thoracic or lumbar region may benefit from VMAT treatment, as it reduces the dose to the bowel and kidneys compared with APPA or three-field treatments.

scholarly journals Comparative effectiveness of treatment modalities in non-metastatic gastric adenocarcinoma: a propensity score matching analysis of the National Cancer Database

2020 ◽  
Vol 7 (1) ◽  
pp. e000483
Author(s):  
Afsaneh Barzi ◽  
Dongyun Yang ◽  
Anthony W Kim ◽  
Manish A Shah ◽  
Sarmad Sadeghi
Keyword(s):  
Radiation Therapy ◽  
Propensity Score ◽  
Gastric Adenocarcinoma ◽  
Neoadjuvant Chemoradiation ◽  
Treatment Modalities ◽  
Future Research ◽  
World Population ◽  
National Cancer Database ◽  
Propensity Score Method ◽  
Curative Surgery

BackgroundWhile addition of chemotherapy and radiation to surgery improves the outcomes of non-metastatic gastric adenocarcinoma (GAC), the best treatment strategy remains controversial.MethodsTo determine the effectiveness of different strategies in patients with curative surgery, we performed an analysis of GAC patients in National Cancer Database. Propensity score method was used to control for imbalances in the confounders. Overall survival (OS), the primary outcome, was analysed using Cox proportional hazard model and Kaplan-Meier curves.ResultsPatients diagnosed with GAC, from 2004 to 2013, were included in this analysis and grouped according to their treatment: surgery alone (15 184), chemoradiation in the neoadjuvant (6000) or adjuvant setting (7953), and perioperative chemotherapy (PCh; 3745) or adjuvant chemotherapy (ACh; 3000). Compared with surgery alone, all adjunctive therapies resulted in an improvement in OS; neoadjuvant chemoradiation (NACRT): HR 0.9 (95% CI: 0.84 to 0.97), PCh: HR 0.73 (95% CI: 0.68 to 0.79), adjuvant chemoradiation (ACRT): HR 0.71 (95% CI: 0.67 to 0.75), and ACh: HR 0.86 (95% CI: 0.8 to 0.93). Excluding patients with surgery only, we compared different strategies to PCh. In patients with distal GAC, ACRT resulted in improved OS, (HR 0.89; 95% CI: 0.796 to 0.996), p=0.042. In patients with proximal GAC, NACRT was inferior to PCh, HR 1.101 (95% CI: 1.006 to 1.204), p=0.036.ConclusionIn this real world population, addition of chemotherapy and radiation to surgery was associated with better OS. Radiation therapy may have a role in patients with distal GAC. Future research can elucidate patient, tumour, and treatment factors that necessitate the inclusion and sequence of radiation therapy in this population.

scholarly journals Proton Therapy in the Treatment of Head and Neck Cancer

2017 ◽  
Vol 8 (2) ◽  
pp. 45-48
Author(s):  
Evangelia Katsoulakis ◽  
Natalya Chernichenko ◽  
David Schreiber
Keyword(s):  
Radiation Therapy ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Proton Therapy ◽  
Clinical Studies ◽  
Intensity Modulated Radiation Therapy ◽  
Added Value ◽  
Treatment Modalities ◽  
Intensity Modulated

ABSTRACT Aim To examine the value of proton therapy in relation to other treatment modalities in head and neck cancer. Review Proton therapy has evolved into more sophisticated and costly intensity-modulated proton therapy and has resulted in even greater dose reduction to normal critical structures at risk as compared with photon therapy. Early clinical studies in head and neck cancers, especially for tumors of the skull base and paranasal sinuses, suggest that proton therapy is excellent in terms of local control and is comparable to intensity-modulated radiation therapy photons but with lower rates of morbidity. Results There are many potential advantages to radiation therapy with protons. While there are many single institution studies examining the added value of protons to photon therapy, the value of proton therapy must be examined in prospective randomized clinical studies and across many subsites of head and neck cancer. Additional evidence is necessary to guide efficient clinical practice, patient selection, and tumors that are most likely to benefit from this treatment modality and justify proton therapy use given its significant cost. How to cite this article Katsoulakis E, Chernichenko N, Schreiber D. Proton Therapy in the Treatment of Head and Neck Cancer. Int J Head Neck Surg 2017;8(2):45-48.

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