Predictive models of toxicity in external radiotherapy

Abstract

Dose-volume modeling of late and acute toxicity in radiotherapy for prostate cancer is a rapidly evolving field of investigation. The availability of individual, 3-dimensional dose distribution and dose-volume histograms (DVHs) permits the quantitative assessment of dose-volume relations for specific endpoints by investigating the correlation between individual dose-volume data and clinical outcomes. These studies often entail a huge effort in collecting data from large populations that have been followed properly for long time. The rectum is the most investigated organ, especially concerning late bleeding, and a good consensus regarding serial-like behavior for this endpoint comes from various investigations. Concerning the bladder, the existence of a clear dose effect when the organ is wholly or partially irradiated is well known. Concerning erectile dysfunctions, the wide use of hormone therapy and drugs against impotence suggests that large, prospectively scored populations will be necessary to definitively assess dose-volume relations.Bowel irradiation during prostate cancer radiotherapy occurs during pelvic lymph node irradiation, and severe acute toxicity has yet to be modeled clearly. Evidence of a correlation between the DVH of the intestinal cavity and bowel toxicity recently was reported, providing important information about optimal dose-volume constraints to be used during whole-pelvis irradiation with intensity-modulated radiotherapy. KEY WORDS: radiotherapy, radiation-induced effects, toxicity, dose-volume models.Dose-volume modeling of late and acute toxicity in the radiotherapy of prostate cancer is a rapidly evolving field of investigation. The prostate is in close proximity to organs at risk, such as the rectum and bladder, which should be spared as much as possible; conversely, evidence of a dose-effect relation in the probability of local control, at least in some subgroups of patients, suggests the advisability of escalation to very high doses. Intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) exploit new tools and methods for dose painting distributions strictly tailored around the planning target volumes (PTV) to reduce the fraction of organs at risk irradiated to moderate/high doses while escalating the dose and/or the dose per fraction.

Hyperbaric oxygen therapy for refractory radiation‐induced hemorrhagic cystitis

“…Consequently, short-and long-term soft tissue lesions on collateral tissues have become relatively common. 8,10,13 Through the increase of tissue oxygenation, angiogenesis and fibroblastic proliferation, hyperbaric oxygen therapy has been shown to be effective in the treatment of radiation-induced soft tissue lesions. 13,20 Hemorrhagic cystitis is one of the most important longterm side-effects of pelvic radiotherapy.…”

“…RT is often used in the treatment of pelvic malignancies . Despite the latest technological advances, collateral soft tissue lesions are still relatively frequent . Because of its high morbidity and mortality, hemorrhagic cystitis is one of the most important late adverse effects of pelvic irradiation .…”

“…[1][2][3][4][5][6][7] Despite the latest technological advances, collateral soft tissue lesions are still relatively frequent. [8][9][10] Because of its high morbidity and mortality, hemorrhagic cystitis is one of the most important late adverse effects of pelvic irradiation. 11,12 Ionizing radiation limits cellular growth and is associated with progressive obliterating endarteritis, and hypocelullar, hypovascular and hypoxic transformation of the vesical mucosa, with edema, ulceration, decreased regeneration and fibrosis, which are responsible for the symptoms of cystitis.…”

Multi-Atlas-Based Segmentation of Pelvic Structures from CT Scans for Planning in Prostate Cancer Radiotherapy

“…Hence the possibilities for achieving better control by increasing the dose are within reach. However, dose escalation is limited by rectal and urinary toxicity ( [11], [12]). Toxicity events (incontinence, rectal bleeding, stool lose) are frequent with standard prescribed doses (70 -80 Gy) and may even significantly increase for higher doses [13].…”

Genomic predictors of prostate cancer therapy outcomes

“…Although radiation dose escalation improves local cancer control [128], it can also increase local toxicity [129]. Late urinary, rectal and sexual morbidity can be debilitating [130], and many models of expected toxicity after EBRT based on clinical and dose intensity have been published [120,131]. However, late toxicity is highly variable, even among patients with identical clinical factors and radiation dose [132] and, thus, other factors may be contributory.…”