scholarly journals The therapeutic ratio is preserved for radiotherapy or cisplatin treatment in BRCA2-mutated prostate cancers

2013 ◽  
Vol 5 (2) ◽  
pp. 31
Author(s):  
Danny Vesprini ◽  
Steven A. Narod ◽  
John Trachtenberg ◽  
Juanita Crook ◽  
Farid Jalali ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Normal Tissue ◽  
Parp Inhibitors ◽  
Therapeutic Ratio ◽  
Normal Tissue Toxicity ◽  
Prostate Cancers ◽  
Precision Radiotherapy

Prostate cancers in patients with a mutation in BRCA2 have earlierdisease onset and an aggressive course, often necessitatingthe use of systemic therapy. However, these tumours are DNArepair-defective and could respond favourably to Parp inhibitors orDNA-damaging agents, depending on the therapeutic ratio (ratio oftumour response to normal tissue toxicity). We describe 3 patientstreated with precision radiotherapy or cisplatin who respondedfavourably to both agents, yet did not suffer undue toxicity. Wereview the concept of treating such patients with agents that areselectively toxic to repair-deficient tumours.

Abstract LB-280: FLASH: A novel paradigm changing tumor irradiation platform that enhances therapeutic ratio by reducing normal tissue toxicity and activating immune pathways

2019 ◽  
Author(s):  
Swati Girdhani ◽  
Eric Abel ◽  
Alexander Katsis ◽  
Andrew Rodriquez ◽  
Shilpa Senapati ◽  
...  
Keyword(s):  
Normal Tissue ◽  
Therapeutic Ratio ◽  
Normal Tissue Toxicity ◽  
Tumor Irradiation ◽  
Immune Pathways

scholarly journals Image Guidance in Radiation Therapy: Techniques and Applications

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Shikha Goyal ◽  
Tejinder Kataria
Keyword(s):  
Radiation Therapy ◽  
Normal Tissue ◽  
Image Guidance ◽  
Normal Tissue Toxicity ◽  
Accurate Position ◽  
Single Method ◽  
Expected Benefits ◽  
Precision Radiotherapy ◽  
The Cost ◽  
High Precision Radiotherapy

In modern day radiotherapy, the emphasis on reduction on volume exposed to high radiotherapy doses, improving treatment precision as well as reducing radiation-related normal tissue toxicity has increased, and thus there is greater importance given to accurate position verification and correction before delivering radiotherapy. At present, several techniques that accomplish these goals impeccably have been developed, though all of them have their limitations. There is no single method available that eliminates treatment-related uncertainties without considerably adding to the cost. However, delivering “high precision radiotherapy” without periodic image guidance would do more harm than treating large volumes to compensate for setup errors. In the present review, we discuss the concept of image guidance in radiotherapy, the current techniques available, and their expected benefits and pitfalls.

Abstract LB-280: FLASH: A novel paradigm changing tumor irradiation platform that enhances therapeutic ratio by reducing normal tissue toxicity and activating immune pathways

2019 ◽  
Author(s):  
Swati Girdhani ◽  
Eric Abel ◽  
Alexander Katsis ◽  
Andrew Rodriquez ◽  
Shilpa Senapati ◽  
...  
Keyword(s):  
Normal Tissue ◽  
Therapeutic Ratio ◽  
Normal Tissue Toxicity ◽  
Tumor Irradiation ◽  
Immune Pathways

Modulation of the Rho/ROCK Pathway in Heart and Lung after Thorax Irradiation Reveals Targets to Improve Normal Tissue Toxicity

2010 ◽  
Vol 11 (11) ◽  
pp. 1395-1404 ◽  
Author(s):  
Virginie Monceau ◽  
Nadia Pasinetti ◽  
Charlotte Schupp ◽  
Fred Pouzoulet ◽  
Paule Opolon ◽  
...  
Keyword(s):  
Normal Tissue ◽  
Normal Tissue Toxicity

Resveratrol as an Adjuvant for Normal Tissues Protection and Tumor Sensitization

2020 ◽  
Vol 20 (2) ◽  
pp. 130-145 ◽  
Author(s):  
Keywan Mortezaee ◽  
Masoud Najafi ◽  
Bagher Farhood ◽  
Amirhossein Ahmadi ◽  
Dheyauldeen Shabeeb ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Clinical Studies ◽  
Normal Tissue ◽  
Medical Science ◽  
Treatment Modalities ◽  
Radiation Toxicity ◽  
Normal Tissues ◽  
Normal Tissue Toxicity

Cancer is one of the most complicated diseases in present-day medical science. Yearly, several studies suggest various strategies for preventing carcinogenesis. Furthermore, experiments for the treatment of cancer with low side effects are ongoing. Chemotherapy, targeted therapy, radiotherapy and immunotherapy are the most common non-invasive strategies for cancer treatment. One of the most challenging issues encountered with these modalities is low effectiveness, as well as normal tissue toxicity for chemo-radiation therapy. The use of some agents as adjuvants has been suggested to improve tumor responses and also alleviate normal tissue toxicity. Resveratrol, a natural flavonoid, has attracted a lot of attention for the management of both tumor and normal tissue responses to various modalities of cancer therapy. As an antioxidant and anti-inflammatory agent, in vitro and in vivo studies show that it is able to mitigate chemo-radiation toxicity in normal tissues. However, clinical studies to confirm the usage of resveratrol as a chemo-radioprotector are lacking. In addition, it can sensitize various types of cancer cells to both chemotherapy drugs and radiation. In recent years, some clinical studies suggested that resveratrol may have an effect on inducing cancer cell killing. Yet, clinical translation of resveratrol has not yielded desirable results for the combination of resveratrol with radiotherapy, targeted therapy or immunotherapy. In this paper, we review the potential role of resveratrol for preserving normal tissues and sensitization of cancer cells in combination with different cancer treatment modalities.

scholarly journals Radioimmunotherapy of PANC-1 human pancreatic cancer xenografts in NOD/SCID or NRG mice with Panitumumab labeled with Auger electron emitting, 111In or β-particle emitting, 177Lu

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Sadaf Aghevlian ◽  
Zhongli Cai ◽  
David Hedley ◽  
Mitchell A. Winnik ◽  
Raymond M. Reilly
Keyword(s):  
Normal Saline ◽  
Normal Tissue ◽  
Auger Electron ◽  
Absorbed Dose ◽  
Clonogenic Survival ◽  
Scid Mice ◽  
Human Pancreatic Cancer ◽  
Cell Counts ◽  
Normal Tissue Toxicity

Abstract Background Epidermal growth factor receptors (EGFR) are overexpressed on > 90% of pancreatic cancers (PnCa) and represent an attractive target for the development of novel therapies, including radioimmunotherapy (RIT). Our aim was to study RIT of subcutaneous (s.c.) PANC-1 human PnCa xenografts in mice using the anti-EGFR monoclonal antibody, panitumumab labeled with Auger electron (AE)-emitting, 111In or β-particle emitting, 177Lu at amounts that were non-toxic to normal tissues. Results Panitumumab was conjugated to DOTA chelators for complexing 111In or 177Lu (panitumumab-DOTA-[111In]In and panitumumab-DOTA-[177Lu]Lu) or to a metal-chelating polymer (MCP) with multiple DOTA to bind 111In (panitumumab-MCP-[111In]In). Panitumumab-DOTA-[177Lu]Lu was more effective per MBq exposure at reducing the clonogenic survival in vitro of PANC-1 cells than panitumumab-DOTA-[111In]In or panitumumab-MCP-[111In]In. Panitumumab-DOTA-[177Lu]Lu caused the greatest density of DNA double-strand breaks (DSBs) in the nucleus measured by immunofluorescence for γ-H2AX. The absorbed dose in the nucleus was 3.9-fold higher for panitumumab-DOTA-[177Lu]Lu than panitumumab-DOTA-[111In]In and 7.7-fold greater than panitumumab-MCP-[111In]In. No normal tissue toxicity was observed in NOD/SCID mice injected intravenously (i.v.) with 10.0 MBq (10 μg; ~ 0.07 nmoles) of panitumumab-DOTA-[111In]In or panitumumab-MCP-[111In]In or in NRG mice injected i.v. with 6.0 MBq (10 μg; ~ 0.07 nmoles) of panitumumab-DOTA-[177Lu]Lu. There was no decrease in complete blood cell counts (CBC) or increased serum alanine aminotransferase (ALT) or creatinine (Cr) or decreased body weight. RIT inhibited the growth of PANC-1 tumours but a 5-fold greater total amount of panitumumab-DOTA-[111In]In or panitumumab-MCP-[111In]In (30 MBq; 30 μg; ~ 0.21 nmoles) administered in three fractionated amounts every three weeks was required to achieve greater or equivalent tumour growth inhibition, respectively, compared to a single amount of panitumumab-DOTA-[177Lu]Lu (6 MBq; 10 μg; ~ 0.07 nmoles). The tumour doubling time (TDT) for NOD/SCID mice with s.c. PANC-1 tumours treated with panitumumab-DOTA-[111In]In or panitumumab-MCP-[111In]In was 51.8 days and 28.1 days, respectively. Panitumumab was ineffective yielding a TDT of 15.3 days vs. 15.6 days for normal saline treated mice. RIT of NRG mice with s.c. PANC-1 tumours with 6.0 MBq (10 μg; ~ 0.07 nmoles) of panitumumab-DOTA-[177Lu]Lu increased the TDT to 20.9 days vs. 11.5 days for panitumumab and 9.1 days for normal saline. The absorbed doses in PANC-1 tumours were 8.8 ± 3.0 Gy and 2.6 ± 0.3 Gy for panitumumab-DOTA-[111In]In and panitumumab-MCP-[111In]In, respectively, and 11.6 ± 4.9 Gy for panitumumab-DOTA-[177Lu]Lu. Conclusion RIT with panitumumab labeled with Auger electron-emitting, 111In or β-particle-emitting, 177Lu inhibited the growth of s.c. PANC-1 tumours in NOD/SCID or NRG mice, at administered amounts that caused no normal tissue toxicity. We conclude that EGFR-targeted RIT is a promising approach to treatment of PnCa.

scholarly journals Anti-oxidant vitamins reduce normal tissue toxicity induced by radio-immunotherapy

2000 ◽  
Vol 86 (2) ◽  
pp. 276-280 ◽  
Author(s):  
Rosalyn D. Blumenthal ◽  
Walter Lew ◽  
Albert Reising ◽  
Danielle Soyne ◽  
Lou Osorio ◽  
...  
Keyword(s):  
Normal Tissue ◽  
Normal Tissue Toxicity ◽  
Anti Oxidant

scholarly journals Germline PALB2 Variants and PARP Inhibitors in Endometrial Cancer

2021 ◽  
Vol 19 (11) ◽  
pp. 1212-1217
Author(s):  
Michael A. Cilento ◽  
Nicola K. Poplawski ◽  
Sellvakumaram Paramasivam ◽  
David M. Thomas ◽  
Ganessan Kichenadasse
Keyword(s):  
Endometrial Carcinoma ◽  
Treatment Options ◽  
Parp Inhibitors ◽  
Response To Treatment ◽  
Parp Inhibition ◽  
Ovarian Cancer Risk ◽  
Additional Question ◽  
Prostate Cancers ◽  
Risk Reducing ◽  
Female Carriers

PARP inhibitors are orally administered antineoplastic agents that affect the homologous recombination (HR) repair pathway, and are approved by the FDA for the treatment of ovarian, breast, pancreatic, and prostate cancers. This report presents a case of recurrent endometrial carcinoma occurring in a woman with a germline pathogenic PALB2 whole-exon deletion. This uncommon finding in a patient with endometrial carcinoma provided the opportunity to use a management strategy of PARP inhibition with olaparib, resulting in a prolonged response to treatment; however, disease progression eventually occurred. Further studies are required to elucidate the mechanisms underlying resistance to PARP inhibition, and the potential future treatment options in this setting. Current recommendations for risk management of female carriers of PALB2 variants focus on breast and ovarian cancer risk. This case raises the additional question of a potential role for risk-reducing hysterectomy in female carriers of PALB2 variants.

Sign in / Sign up

Export Citation Format

Share Document